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Fertility Preservation: Current and Future Perspectives for Oncologic Patients at Risk for Iatrogenic Premature Ovarian Insufficiency
Progress in recent years in the efficacy of oncologic treatment and early diagnosis of cancer has determined an increase in life expectance in cancer patients. About 10% of all cancer cases affect women younger than 45 years; therefore nowadays approximately 5-6% of the population in childbearing age consists in cancer survivors. A crucial issue is the high risk of premature ovarian insufficiency due to possible gonadotoxic effects of oncologic treatments. Considering combined chemotherapy, radiation therapy, and bone marrow transplantation, this risk can reach 92-100%, depending on the age and ovarian reserve of the patient, as well as the schedule and type of therapy. International guidelines recommend addressing all the patients diagnosed with a neoplasia treatable with potentially gonadotoxic therapies to fertility preservation. Moreover, fertility preservation also seems to reserve fascinating implications for women who want to delay childbearing for social reasons or women affected with endometriosis, who could receive unexpected opportunities. At present, the most widespread techniques to preserve fertility in adult women are embryo or oocyte cryopreservation, depending on the presence of a partner or according to legislative issues, but these procedures require time for ovarian stimulation. In prepubertal patients or when there is no possibility of delaying chemotherapy, ovarian tissue cryopreservation and subsequent transplantation represent the main strategy.
The issue of infertility epidemic is actual and troubling in most western countries as well in large part of the developed world. In fact, the decrease of young people who have to sustain elderly people is an alarming problem for those countries’ economies . Based on recent cancer statistics, a woman’s probability of being diagnosed with an invasive cancer from birth to 49 years is 5.4% (1/18) .
In recent years, progress in the efficacy of oncologic treatment and in early diagnosis of cancer has determined an increase in life expectancy in cancer patients . Therefore, approximately 6% of the population in childbearing age nowadays consists in cancer survivors .
At the same time complex ethical matters are raising in infertility centers together with the introduction of the newest fertility preservation procedures.
An unpleasant side effect of some chemo- and radiotherapy is premature ovarian insufficiency (POI) after treatment. When these treatments are combined with bone marrow transplantation, the risk of POI is even greater .
Particularly, some anticancer drugs can reduce the primordial follicle pool, induce ovarian atrophy and fibrosis of ovarian cortex, and damage gonadal vascularization . However, it is well known that the effects of gonadotoxic drugs are not always the same, depending on type and dose of drug and on age and pretreatment ovarian reserve of the patient . The effect can range from complete premature ovarian insufficiency (POI) to partial reduction of ovarian reserve.
2. Cancer Patients That Could Benefit from the Ovarian Tissue Cryopreservation
The American Society of Clinical Oncology (ASCO) in 2006 suggested the stratification of patients in high, intermediate, and low risk of ovarian insufficiency subsequent to oncologic treatments, depending on treatment regimen .
For example, standard first line treatment of Hodgkin lymphoma (HL) is ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine), which is considered to have a low risk of POI in reproductive age (< 10 %) .
On the contrary, patients undergoing regimens containing alkylating agents or hematopoietic stem cell transplant (HSCT) are strongly advised to consider fertility cryopreservation, having a POI rate of 70-100 %. The chances of becoming pregnant after these treatments are as low as 3-8 % .
Also, ionizing radiation on the pelvis can cause dose-dependent damage to DNA with estimated survival of only 50% of primordial follicles following a dose of <2 Gy. A dose of 5-10 Gy is considered toxic for oocytes .
3. Ovarian Reserve
It is crucial to give each patient adequate counselling regarding her risk of developing POI after oncologic treatment, but it is extremely difficult to forecast an exact percentage of risk.
The concept of “ovarian reserve” refers to the pool of primordial follicles contained in both ovaries at each stage of a woman’s life and depends on the quantity of primordial germ cells that migrate in the ovaries during fetal development. Already during gestation, the great majority of these germ cells are lost before birth, and the process of depletion continues until puberty, when a woman owns around 300.000-400.000 primordial follicles in both ovaries, but this number varies greatly from one woman to another, depending on causative factors only partially elucidated [10–12].
After menarche, each month a woman loses a variable number of follicles in the process of selection of dominant follicle, so the decline in the follicular pool continues until menopause.
First, the age of the patient is decisive, as after age 35-38 years the ovarian reserve is consistently reduced. Beyond the number of remaining oocytes in the ovary, another crucial factor depending on patient’s age is oocyte quality, which may influence the prognosis of therapeutic strategies for fertility preservation . Moreover, each patient has a different ovarian reserve depending on genetic and environmental factors, so it is mandatory to evaluate pretreatment ovarian reserve analyzing antimullerian hormone (AMH), antral follicle count (AFC) through ultrasound (US), and, when possible, follicle-stimulating hormone (FSH) and estradiol on second-third day of menstrual cycle [13, 14].
Level of circulating AMH seems to be the most reliable parameter of ovarian reserve, as it does not fluctuate among various cycles and does not vary among different phases of menstrual cycles.
However, technical issues such as improper storage and handling of samples, delayed centrifugation, storage at room temperature can drastically interfere with the correct evaluation of AMH levels. Standardization of measurement method of AMH combined with a stable automated assay is likely to improve its performance in predicting the ovarian reserve .
The proper integration of AMH levels and AFC is desirable to have a correct evaluation of the ovarian reserve before the selection of fertility preservation technique.
4. Options for Fertility Preservation (Table 1)
4.1. Gonadotropin-Releasing Hormone (Gn-RH) Agonists
The cotreatment of cancer patients with Gn-RH agonist during oncologic therapies has been used for decades. The rationale of this procedure is the evidence that maintenance of ovarian function after this treatment is more frequent in girls treated before puberty, than in women treated after menarche . However, the efficacy of this strategy of fertility preservation is little discussed.
Meta-analyses conducted so far have shown that cotreatment with Gn-RH analogues may give a higher chance of restoration of menstrual cycle after cancer treatment but probably does not reduce gonadotoxicity of oncologic treatments, as it does not seem to improve the clinical pregnancy rate and the fertility potential by resuming spontaneous ovulation [19, 20].
A recent meta-analysis by Elgindy and colleagues, in 2015, examined 10 trials published on 907 women to evaluate whether Gn-RH analogues coadministration during chemotherapy can reduce ovarian gonadotoxicity . Researchers concluded that Gn-RH agonists cotreatment did not significantly increase ovarian function resumption, nor any parameter of evaluation of ovarian reserve. Also, spontaneous pregnancy rates were comparable between patients who underwent cotreatment and women who were submitted to chemotherapy alone.
A long-term analysis published in 2016 evaluating 67 patients affected by lymphoma compared the fertility outcome of patients cotreated with the Gn-RH agonist Triptorelin versus patients who underwent chemotherapy alone. Multivariate logistic regression analysis showed that there was a significant association between risk of POI and age, the conditioning regimen for hematopoietic stem cell transplant, and the total dose of cyclophosphamide but that the coadministration of Gn-RH agonist during chemotherapy did not significantly affect ovarian reserve posttreatment and pregnancy rate .
Although the ASCO Clinical Practice guidelines suggest that cotreatment with Gn-RH analogues may have some medical benefits such as the reduction of abnormal vaginal bleeding in patients with low platelet count consequent to chemotherapy, they state that there is insufficient evidence that Gn-RH analogues are a reliable method to preserve fertility, in view of the cost and potential relevant side effects such as bone loss, hot flushes, and possible interference with response to cancer treatment in estrogen-sensitive cancer .
4.2. Ovarian Transposition (Oophoropexy)
Oophoropexy is a procedure which consists in ovarian transposition out of the field of radiation in patients undergoing pelvic or lower abdomen radiation as only cancer treatment. This technique seems to be underused, despite it being a relatively simple and quick laparoscopic surgical procedure that does not require delaying radiotherapy [4, 23].
Indications for the technique are gynecological cancer such as cervical, vaginal, and uterine carcinomas or ovarian dysgerminoma. Other possible indications are nongynecological cancers like osteosarcoma, rhabdomyosarcoma, Hodgkin’s lymphoma, anorectal cancer, and medulloblastoma [24, 25].
The rates of fertility preservation vary depending on the regimen of radiation used: 90% of patients who underwent vaginal brachytherapy and 60% of patients who underwent external radiation therapy with vaginal brachytherapy after surgery had their ovarian function preserved [4, 24].
During ovarian transposition, the ovaries are mobilized with their blood supply from the infundibulopelvic ligament and then fixed with permanent suture to the anterior abdominal wall, in a lateral position, 3–4 cm above the umbilical line [23, 24]. Metallic clips are usually positioned at the level of sutures, to identify the ovaries when planning radiotherapy.
However, the technique is not always successful, because of radiation scatter. Especially in women older than 40 years, ovarian reserve is too scarce to be preserved, even with oophoropexy. Moreover, sometimes adjuvant chemotherapy can be necessary, and in these cases the risk of POI cannot be avoided by ovarian transposition alone . In view of the above, during laparoscopy it could be advisable to take ovarian biopsies for ovarian tissue cryopreservation . It should be remembered that this surgical procedure requires a general anesthesia and that surgery can always have the described complications of laparoscopy.
A further limitation of the technique is the theoretical possibility of havng ovarian localization of the primary tumor, so it is mandatory to inform patients of this risk and to exclude tumors with a high risk of ovarian metastases from this procedure. In view of the above-mentioned limitations, ovarian transposition remains experimental as a method to preserve fertility.
4.3. Embryo Cryopreservation
At present, embryo cryopreservation is the main resource for a woman at risk of iatrogenic POI who has childbearing desire .
The technique is well established in fertility programs, and it is used when there are supernumerary embryos in assisted reproduction technologies (ART) cycles, when there is risk of ovarian hyperstimulation syndrome, or in other circumstances.
However, the possibility is feasible only for postpubertal women with a partner (or using donor sperm), and the technique has ethical and legal issues to consider: in some countries, embryo cryopreservation is forbidden by law both in ART and fertility preservation, and embryo cryopreservation is performed notwithstanding the current regulations in very specific cases . Moreover, cryopreserved embryos belong to the couple of parents, and this aspect may be problematic to manage after many years from cryopreservation, as relationships can end.
Another limit of the procedure is that it gives the woman the possibility of pregnancy but does not restore her fertility, having no effects on cycle restoration or resuming ovulation. Therefore, spontaneous conception is not possible.
Finally, the procedure is not practicable in patients who need to begin chemotherapy as soon as possible, as it requires 10-15 days for controlled ovarian stimulation (COS) to induce multiple follicular growth and oocytes pick up.
4.4. Oocyte Cryopreservation
In young patients with no need to urgently begin chemo/radiotherapy, oocytes cryopreservation after COS is considered a good option for future pregnancy perspectives. The recent progress in oocyte vitrification has led to results comparable to ART cycles with fresh oocytes [26–33].
Nowadays oocyte cryopreservation, together with embryo cryopreservation, is considered a well-established method for fertility preservation [22, 27]. Potential advantages of this technique also can be undertaken by single women and there is theoretically no risk of malignant cells reimplantation when it is performed in oncologic patients. Despite this, the method provides the possibility of obtaining a pregnancy but does not restore fertility of oncologic women faced with iatrogenic POI, nor spontaneous ovulation. It is not feasible for prepubertal girls, as it requires sexual maturity, nor for patients with the urgent need to undergo oncologic treatments. Indeed, two weeks is generally needed for COS. However with the background of the efficacy of the “emergency schedule” starting COS in the luteal phase, it allows maximizing the chances of success . Recently a new stimulation protocol providing for a double stimulation in both follicular and luteal phase of the same menstrual cycle has been proposed with the aim of maximizing the number of oocytes retrieved in a single cycle . However, women should be counselled that age at the time of fertility preservation is strongly related to the chances of success, as oocyte age determines pregnancy rate.
A recent study by Cobo retrospectively analyzed their clinical data to assess the estimated live birth rate per oocyte in women aged ≤35 and ≥36 years. The authors found a 60.5% likelihood of live birth in women ≤35 years considering a pool of 10 mature oocytes used, while the likelihood of live birth was only 29.7% for the same number of oocytes used . The same relation of patient’s age with chances of live birth rate after ART cycles using thawed oocytes was confirmed by Goldman and colleagues , who developed a model to predict patient’s chances of pregnancy depending on age and the number of oocytes retrieved.
It is therefore recommended to carefully consider patient’s age before submitting her to COS and pick up, informing her of the real possibility of pregnancy based on her ovarian reserve.
Another crucial aspect is the performance of the technique based on the number of oocytes retrieved. Among the most cited papers on the topic, the work of Sunkara and colleagues in 2011 showed a nonlinear relationship between the number of oocytes retrieved and the chances of pregnancy following IVF treatment .
Moreover, in highly qualified ART centers, the live birth rate per vitrified oocyte is reported around 5.7%, thereby approximately 10 oocytes are needed to give patient a real chance of pregnancy [3, 28–30, 36]. And it is important also not to forget that the great majority of the studies regarding the performance of thawed oocytes in ART is extrapolated by studies on infertile, nononcologic patients, but there is growing evidence that patients with certain specific cancers or patients with known mutations of BRCA gene could have a reduced ovarian reserve connected to the malignancy [38, 39]. More studies are needed to elucidate the topic.
Some authors advise against submitting to COS for oocyte or embryo cryopreservation women with hormone-sensitive cancers . However, there is good evidence in literature regarding the safety of these procedure using combination protocols including Aromatase Inhibitors, such as Letrozole, associated with standard Gn-RH antagonist stimulation protocols, to avoid the supraphysiological increase in estrogens after COS [41–45]. The data in literature show comparable pregnancy rate to infertile population undergoing IVF and embryo transfer (IVF-ET) . Nevertheless, concerns exist about the possible role of progesterone in hormone-dependent cancers, as the cotreatment with Letrozole has shown to not influence progesterone levels during COS in fertility preservation ART cycles . A recent systematic review concludes that a detrimental effect on disease-free survival period in breast cancer women submitted to COS with Letrozole supplementation is not demonstrated in available evidence, but high-quality evidence is lacking. So, combined protocols using Letrozole 5 mg daily administrated during COS are recommended, but a slight effect on the possibility of recurrence in breast cancer is not excluded . More studies on larger populations with longer follow-up periods are therefore required to clarify this topic.
4.5. Ovarian Tissue Cryopreservation and Grafting
Ovarian tissue cryopreservation and subsequent reimplantation are now the only available option for fertility preservation in prepubertal girls and patients who cannot delay the start of oncologic treatments. The great advantage of this method is that with grafting of thawed ovarian tissue not only pregnancy chances but also ovarian endocrine function is restored, and natural pregnancy can be achieved. When cryopreservation and storage of ovarian tissue are performed in prepubertal girls, successful subsequent grafting may also allow induced puberty [3, 47]. Regrettably, this technique presents age limitation, due to the scarcity of primordial follicles contained in the ovaries after 35-36 years .
Possible indications for this procedure are malignant disease or other disorders that require potentially gonadotoxic treatments, such as autoimmune diseases necessitating treatment with cyclophosphamide, severe endometriosis requiring extensive surgical eradication, genetic syndromes at risk of POI, or benign hematological diseases requiring bone marrow transplantation .
Unfortunately at present ovarian tissue cryopreservation and subsequent grafting are considered an experimental procedure, mainly due to the scarcity of definite data published in literature on the outcome of the technique [40, 48]. In fact, many papers have been published on successful pregnancies obtained in women after transplantation of cryopreserved tissue, but few articles report the effective total number of transplantations performed, and the majority of papers regarding this issue are case reports or case series regarding successful pregnancies, rather than failures [4, 49].
Ovarian tissue cryopreservation can be performed by laparoscopy, and 4-5 ovarian cortex slices of ≈1 cm in length, 4-5 mm in width, and 1.0-1.5 mm in depth are generally taken, reducing as far as possible the use of electrocoagulation to decrease ovarian cortex injury and consequent loss of primordial follicles . In very young children, where ovarian volume is considerably lower, unilateral oophorectomy can be performed, especially when the risk of iatrogenic POI after the therapies is high [3, 51]. It is important to leave one ovary in situ, to allow future orthotopic reimplantation. Histopathologic exams can be made on one of the fragments to analyze the possible presence of malignant cells and evaluate the density of primordial follicles.
The site of subsequent grafting can be orthotopic or heterotopic. To date, the first option is preferred, firstly because it may possibly lead to spontaneous conception and because of the pelvic cavity supply with the ideal microenvironment to support the engraftment . The technique of orthotopic grafting consists in the placement of the thawed ovarian tissue fragments in a “peritoneal window” of the ovarian fossa or preferably closely to the medulla of the remaining ovary, after making an incision in the cortex . The ovarian slices are then fixed to their new location by interrupted sutures . The technique requires abdominal surgery, usually carried out by laparoscopy, under general anesthesia. It is useful to perform laparoscopic tubal patency test during surgery, to refer patients to ART when necessary. Some authors suggest executing the procedure in two steps, by preparing a peritoneal pocket or preparing the ovarian tissue for subsequent transplantation in a first laparoscopy, to allow optimal angiogenesis to supply the graft, and then a “second step” after approximately one week .
Heterotopic grafting means transplantation of thawed ovarian cortex tissue outside the pelvic cavity. It can be performed in subcutaneous tissue of the abdomen or in the forearm. This method can be preferable in cases of severe pelvic adhesions or anatomic changes secondary to radiation therapy, which could impair vascularization to the graft causing ischemic injury. It does not require general anesthesia, and the graft can be easily accessible for ultrasound during COS and oocyte pick up. However, this method does not allow spontaneous conception.
Concerning the outcome of ovarian tissue cryopreservation as a fertility preservation method, some retrospective cohorts have been recently published by the most experienced research groups, with live birth rates reported around 23 to 37% [3, 51–56]. A recent meta-analysis by Pacheco and Oktay reported a cumulative clinical and live birth plus ongoing pregnancy rate of 57.5% and 37.7%, respectively, with an endocrine restoration rate of 63.9% . Mean duration of ovarian function after grafting has been reported about 5-10 years, with a variability mainly due to age at the time of the cryopreservation, previous gonadotoxic treatments, and the volume of ovarian tissue removed, but it should be considered that the procedure can be repeated . Unfortunately, transplanted ovarian tissue seems to undergo an initial over-recruitment of follicles and a dysfunctional folliculogenesis which determine an acute impairment of follicular pool in grafted tissue, with loss of approximately 50% of follicles, because of ischemia and oxidative stress damage [4, 57].
Some factors can thus influence the lifespan of the graft, such as the treatment with antioxidants or vascular growth factors, on which research is focusing to increase the chances of success of the technique [57–60]. In 2016, Oktay and colleagues obtained two life births in patients with iatrogenic POI after transplantation of cryopreserved ovarian tissue with a human decellularized extracellular tissue matrix scaffold, to minimize oxidative stress damage secondary to ischemia . More research is needed on this topic to maximize the chance of successful growth of grafted ovarian tissue.
5. Risk of Reimplanting Malignant Cells with Transplanted Cryopreserved Ovarian Tissue
Ovarian tissue cryopreservation followed by orthotopic reimplantation represents the main option to preserve fertility for prepubertal girls or oncologic patients undergoing immediate gonadotoxic cancer treatment, as oocyte and embryo cryopreservation techniques require a prior course of hormonal stimulation .
The serious concern that remains regarding the safety of ovarian tissue preservation and subsequent grafting is the possibility of harvesting, cryopreserving, and subsequently reintroducing malignant cells present in the ovarian cortex tissue yielded. These cells in fact could lead to primary cancer recurrence within the grafted tissue .
According to data in literature, hematologic cancers represent the most frequent indication for ovarian tissue cryopreservation, accounting for more than 1/3 of total cases.
Unfortunately, although rare, ovarian metastases have been described in a large part of malignancies, including leukemia, HL and NHL, breast cancer, renal tumors, Ewing’s sarcoma, gastrointestinal system cancers, and neuroblastoma .
The risk of ovarian metastases from nongynecologic cancers seems higher for gastric carcinoma (55.8%), followed by colon carcinoma (26.6%), breast cancer (24.2%), lung cancer (23.4%), and lymphoma (13.3%), whereas the reported rate for uterine carcinoma ranges from 13.1% to 22%) . A different issue is represented by acute leukemia that is a blood-disseminated disease and is hence considered at very high risk for ovarian metastases (> 50%) .
Although the relatively considerable rate of ovarian metastases reported in literature mandates concerns in grafting ovarian tissue, most data refer to research based on autopsies and therefore do not necessarily reproduce identical clinical risks especially for the women in complete disease remission and with a favorable prognosis who are offered cryopreservation of ovarian cortex.
By molecular biology studies, especially with Polymerase Chain Reaction (PCR), cancer cells have been identified in ovarian cortical samples in more than 50% of women affected by acute leukemia .
Apart from general data, as a matter of fact the actual risk of transferring diseased cells together with the grafted ovarian tissue is subject to the complete remission of disease, the type of leukemia, and how chemotherapy is administered .
Therefore, it is mandatory to establish minimal residual disease (MRD) in patients affected by hematologic diseases before planning yield and subsequent frozen-thawed reimplantation of ovarian tissue .
Unfortunately, evidence from literature concerning this topic is still based on research of low-moderate quality and therefore interpretation of available data must be evaluated with caution.
In consideration of the peculiarity of disease, even if further studies are needed, before cryopreservation, other options as In Vitro Maturation (IVM)  or isolated follicle transplantation should be considered for such women with the aim of eluding chemotherapy jeopardizing the pool of primordial follicles.
5.2. Hodgkin’s Lymphoma
Published literature concerning the risks of transferring malignant cells in women affected by HL is as yet associated with a very low-quality evidence .
To date, despite occasional reports of ovarian involvement by high stage HL, mainly by autopsy studies, there is a growing testimony of the safety of ovarian tissue cryopreservation, described by several authors, with a relatively large series of 15 cases demonstrating no recurrences with a maximum follow-up of 8 years .
5.3. Non-Hodgkin’s Lymphoma
All studies but two confirmed the safety of frozen ovarian tissue autotransplantation in women affected by NHL .
5.4. Breast Cancer
Since breast cancer represents the most frequent malignancy in women and about 5% of cases occurs in women under the age of 40 years, several studies have been performed to investigate risks and outcomes of harvesting and reimplanting cryopreserved ovarian cortex in patients with the disease .
Whereas in advanced stage patients the risk of ovarian metastases (13.2-37.8%) commands prudence in ovarian tissue autotransplantation, in early stage disease growing evidence of the safety, feasibility, and success of transferring cryopreserved ovarian cortex seems to give encouraging new horizons for such patients.
5.5. Cervical Carcinoma
Considering that ovarian involvement is known to be noticeably more common in adenocarcinoma (up to 6.8%) than in the usual squamous cell histotype (0.7-2.5%), no evidence of relapse from the grafted tissue has been demonstrated in all the most recent series published in literature .
5.6. Endometrial Carcinoma
The reported risk of ovarian malignant cells in women affected by endometrial cancer seems directly related to the stage of disease, being anyway very low in the frequent early stage endometrial carcinoma (1.9% in Federation of Obstetricians and Gynecologists (FIGO) stage 1 tumors) .
5.7. Central Nervous System Tumors
Primitive neuroectodermal tumors (PNETs) like medulloblastoma and neuroblastoma are classified in two types: central nervous system PNET and peripheral PNET (Ewing sarcoma).
Despite single successful reports of transplantation of frozen-thawed ovarian tissue in children, Ewing sarcoma is still considered at moderate risk for ovarian involvement, whereas neuroblastoma is categorized together with leukemia and Burkitt lymphoma in the high-risk group for ovarian metastasis by most authors .
5.8. Colorectal Carcinoma
Very few case reports (mainly autopsy studies) detected no malignant cells in ovarian tissue from patients affected by colorectal cancer, but on the contrary the possible ovarian involvement by rectal cancer is well described and therefore no definitive conclusions can be drawn concerning safety and efficacy of fertility preservation procedures for such women yet .
6. Future Perspectives
6.1. In Vitro Maturation (IVM)
IVM of immature ovarian follicles collected from ovarian tissue at the time of cryopreservation could be a promising option for patients affected with types of cancer at high risk of ovarian localization, which should be advised against ovarian tissue cryopreservation and subsequent grafting for the high risk of relapse .
This technique consists in the aspiration of immature oocytes from preantral and small antral ovarian follicles present in ovarian tissue before or after ovarian tissue withdrawal and the subsequent incubation in a maturation medium, with final vitrification of mature oocytes or cryopreservation of embryos produced with IVF .
This method can be applied also in prepubertal girls, independently from cycle phase, and allow subsequent IVF and pregnancy, decreasing the risk of reimplantation of malignant cells. IVM is currently adopted in many ART centers with a 20 to 35% live birth rate from cryopreserved IVM oocytes, but more research is needed regarding the application in the specific field of fertility preservation to improve cryopreservation protocols and culture media [4, 66–69].
6.2. “Artificial Ovary”
Great interest has been awakening in recent years for the possibility of creating an “artificial ovary”, with the objective of reducing the possibility of disseminating malignant cells and maximizing the chances of survival and growth of isolated follicles and ovarian cells, recreating their optimal microenvironment [70–73].
The concept of the “artificial ovary” consists in the packaging of oocytes and follicular cells in a biodegradable scaffold to maintain the three-dimensional structure. The scaffold should be constituted of a matrix to maintain the interactions between the oocyte and granulosa cells, in the while revascularization occurs. In 2012 Vanacker and colleagues first experimented a biodegradable matrix of alginate hydrogel containing isolated follicles and ovarian cells, transplanted in a peritoneal pocket in immunocompetent mice . Further research which focused on the study of other materials is needed to increase the survival of the grafting by reducing the damage resulting from ischemia and oxidative stress .
The progresses in oncologic treatments with consequently more women affected by iatrogenic POI as well as the postponing of childbearing in women, with consequent low chances of pregnancy due to scarce ovarian reserve, are raising interest concerning the possibility of preserving fertility.
In its most recent guidelines ASCO has clarified the requirement to address all the women requiring potentially gonadotoxic treatments to fertility preservation options, irrespective of age, parity, or prognosis .
At present oocyte and embryo cryopreservation are the main fertility preservation options for postpuberal women who can delay treatments for 10-15 days, as they are the only techniques approved as fertility preservation options at the moment. Nevertheless, patients undergoing COS for fertility preservation are generally not infertile women; therefore they can be easily responsive also to mild gonadotrophins stimulation schedules.
On the other hand, ovarian tissue cryopreservation is currently the only option for prepuberal girls or patients who require immediate treatments, but it is still considered an experimental technique until more research will assure its complete safety.
Finally, to increase the chances of success, in the future a combination of techniques could probably be adopted, for example, by administering COS before oocyte aspiration and subsequent ovarian tissue withdrawal and cryopreservation. This procedure could allow cryopreservation of both IVM oocytes and ovarian tissue, also for isolated follicles and ovarian cells grafting, thus potentially minimizing the risk of neoplastic dissemination.
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this article.
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P. S. Uzelac, A. A. Delaney, G. L. Christensen, H. C. L. Bohler, and S. T. Nakajima, “Live birth following in vitro maturation of oocytes retrieved from extracorporeal ovarian tissue aspiration and embryo cryopreservation for 5 years,” Fertility and Sterility, vol. 104, no. 5, pp. 1258–1260, 2015.View at: Publisher Site | Google Scholar
V. Luyckx, M.-M. Dolmans, J. Vanacker et al., “A new step toward the artificial ovary: Survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold,” Fertility and Sterility, vol. 101, no. 4, pp. 1149–1156, 2014.View at: Publisher Site | Google Scholar
V. Luyckx, M.-M. Dolmans, J. Vanacker, S. R. Scalercio, J. Donnez, and C. A. Amorim, “First step in developing a 3D biodegradable fibrin scaffold for an artificial ovary,” Journal of Ovarian Research, vol. 6, no. 1, 2013.View at: Google Scholar
J. Vanacker, V. Luyckx, M.-M. Dolmans et al., “Transplantation of an alginate-matrigel matrix containing isolated ovarian cells: First step in developing a biodegradable scaffold to transplant isolated preantral follicles and ovarian cells,” Biomaterials, vol. 33, no. 26, pp. 6079–6085, 2012.View at: Publisher Site | Google Scholar


Here’s the latest news out of Pennsylvania courtesy of Monmouth University’s latest poll:
Joe Biden holds a 4-point lead over Donald Trump among all registered voters in Pennsylvania according to the Monmouth (“Mon-muth”) University Poll. Among likely voters, the race is a tight 1 to 3 points, depending on the expected turnout level. This shift from Biden’s larger lead just over six weeks ago is due to declining support for the challenger among men, voters under age 50, and voters in key swing counties. The generic House ballot also remains close, while Democrats are in a generally better position in a trio of contests for statewide offices. The poll also finds that a small, but important, portion of the electorate agrees with the Republican message that the American suburbs are under threat.
Among all registered voters in Pennsylvania, the race for president stands at 49% for Biden and 45% for Trump. Another 2% support Libertarian Jo Jorgensen, less than 1% back the Green Party’s Howie Hawkins, and 4% are undecided. Voter intent includes 43% who say they are certain to vote for Biden (versus 44% who say they are not at all likely to support the Democrat) and 40% who are certain to support Trump (versus 47% who are not at all likely).
The contest tightens when different likely voter models are applied. A model based on a somewhat higher level of turnout than 2016 puts the race at 49% for Biden and 46% for Trump, while one reflecting lower turnout has it at 48% for Biden and 47% for Trump.
NOTE: Monmouth conducted a statewide random sample of 400 Pennsylvania voters from August 28 to 31, 2020.
They also tested down ballot races in Pennsylvania:
It’s important for us to win big in both Biden and mine’s home state and we need to keep up the momentum. Click below to donate and get involved with the Biden-Harris ticket along with their fellow Pennsylvania Democrats campaigns:


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Whatever the economic climate your business can save money by dramatically cutting the cost of your phone bills.
We can reduce the cost of your calls and line rental by our ability to bulk-buy line time and then pass those savings on to you.
And with our great customer service and one simple bill each month there’s really no reason why you shouldn’t receive the benefits of BWN Telecom today.
Get in touch to find out exactly how much you could be saving. BWN Telecom: greater efficiency = lower costs.

domain: finance


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|Full Description: Dragon Fruit variety 'GIANT VIETNAMESE' has a large 1 Lb. to 2 pound (453.6 g-.9072 kg) white fleshed fruit. Exterior is pinkish with long fins. Whole fruit is oval in shape. Sweet and crisp with a watermellon like texture. Growth is robust with dark green stems, thick 3 sided stem growth. Hylocereus undatus X selection. This variety is self pollinating.|
Blooms are nocturnal, white with yellow/gold back petals, over 15" in diameter. Tends to bloom late in the season from Sept. to October, fruits are ready for harvest late November to December depending on your climate at your location.
NOTES; Very simular in growth to 'Vietnamese White' & 'Bien Hoa White'. Fruit exterior color and pulp is also very simular to these 2 varieties, with this variety being more oval in fruit shape or form. Huge fruits with most fruit averaging over 1 pound and many 2 lbs in size as shown pictured.
( Below are more pictures of 'GIANT VIETNAMESE' fruit shown whole & halved ).
Established 5 gallon plant(s) up to specimen sized 15 gallon size plant(s) are also available for shipping within the U.S. only or for pick-up as most are very large, so sorry but no international shipping of large plants.
Simply click the link below for info. about our walk-in nursery website, or to check availability and place an order today with one of our friendly sales reps.!

domain: agronomy


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Sadie Lee makes realistic paintings of real people. Her challenging work first came to wider public attention when her painting Erect, a double portrait of Lee and her then partner sitting side by side in a stiff embrace, was selected for exhibition in the National Portrait Gallery’s annual BP Portrait Award in 1992. The painting was used as the image to publicise the show and was made into posters, displayed on tube station platforms, in magazines and shop windows across London. The image, with an ambiguous but clearly unconventional queer narrative, caught the imagination of a production company and a short film showing how the poster was defaced, sometimes with homophobic graffiti, was shown on Channel 4 as part of that year’s Out on Tuesday programme.
Lee’s work has been selected for exhibition in the BP Awards six times, being commended in 1998 and winning the Travel Award in 1996. The Travel Award enabled Lee to visit the Exotic World Burlesque Museum in California’s Mojave Desert, to meet and make studies of elderly women who were Burlesque Dancers in their youth. The resulting collection A Dying Art: Ladies of the Burlesque was shown as a one-woman exhibition at the National Portrait Gallery in 1997 and travelled to various galleries in the UK for a year.
Lee’s first one-woman show, Venus Envy, was at Manchester City Gallery in 1994, as part of the It’s Queer Up North Festival. She has since had one- woman shows at Salford Museum and Art Gallery, Schwules Museum, Berlin and the Museum of Modern Art, Slovenia. Group shows include exhibitions at the I.C.A., the Museum of London and Glasgow Gallery of Modern Art.
Sadie Lee regularly teaches art workshops at the Wallace Collection and for the past 15 years has worked with the Secondary, Public and Adult Programmes at the National Portrait Gallery as a freelance art educator. In 2005 the NPG invited her to lead a quarterly tour, Queer Perspectives, where she and an invited guest would select and discuss works in the collection that they considered to have a queer subtext. This immensely popular tour regularly attracts audiences of up to 100 people. Past guests have included the singer David McAlmont, author Ali Smith and playwright Neil Bartlett. Its popularity has led to Lee being invited to talk about Queer Perspectives and be involved at similar events at Tate Modern and the Victoria and Albert Museum.
Sadie Lee lives and works in London.
Sadie Lee makes realistic paintings of real people. Recurring themes in her work deal with gender, sexuality, the representation of women and ageing. Her challenging paintings are often compared to the dark figurative work of New Objectivity artists of the 1930’s, such as Christian Schad and Otto Dix.

domain: artistic


This mobile application uses sensor fusion, augmented reality, and reality capturing technology to let your mobile device draw a floor plan for you.
Spelling more bad news for BlackBerry, The Mall of America has picked Nokia’s Lumia 920 as its phone of choice.
Home Depot is pulling nearly 10,000 Blackberry phones from its incentive plans for executives today and replacing them with iPhones.
A simple Swingline stapler from the office supply chain Staples could cost you either $15.79 or $14.29, depending on where you live.
It’s hardly a secret that Americans not only consume massive amounts of food everywhere but also throw massive amounts away. Fortunately, a scrappy startup called EcoScraps is doing its part to remedy one of these problems. The company announced today that it has raised $1.5 million in its first round of funding, which will enable the team to expand operations into more stores and regions across the United States.
Guest Post PayPal is set to announce a major new payments service tomorrow. According to a GigaOm report, it plans to introduce a dongle that will compete with Square and Intuit’s GoPayment product.
Google Maps for Android has just launched a new update that tackles some of the toughest navigation challenges around: the interior world.


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During the process of creating, artists often unearth stories from their memories. A testament to the many facets of personal family history, Bloodlines is an exhibition of encaustic artworks by Flo Bartell on view at the San Luis Obispo Museum of Art's McMeen Gallery from December 2, 2016 — January 29, 2017. Click image for more...
to Jan 29
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Two books teaches length tension assessment techniques
Length Tension Testing provides clear and comprehensive descriptions and photos for assessing flexibility and length tension in the muscles of the lower quadrant.
July 30, 2015 By Kyle Arguelles
Book 1, Lower Quadrant includes techniques for the lumbar spine and pelvis, hip, knee, and foot and ankle, while Book 2, Upper Quadrant features techniques for the cervical spine, temporomandibular joint, thoracic spine, shoulder, elbow, and wrist and hand.
Each technique listing includes concise, standardized descriptions of the actions and positions involved, high-quality colour photos and alternative positions to accommodate patient variability and comfort. Most of these tests can be adapted into treatment techniques. These resources are designed to help physiotherapists, kinesiologists, chiropractors, massage therapists, and osteopaths improve patient care, and they will be invaluable references for students at the college and university level, book proponents say.
Length Tension Testing is written by Paolo Sanzo and Murray MacHutchon. Sanzo is an assistant professor in the school of kinesiology and the Northern Ontario School of Medicine at Lakehead University. A practicing physiotherapist at the Victoriaville Physiotherapy Centre in Thunder Bay, Ont., Sanzo is also an examiner and instructor with the Orthopaedic Division of the Canadian Physiotherapy Association. MacHutchon is a physiotherapist at Pembina Physiotherapy and Sports Injury Clinic in Winnipeg, Man. He is also an examiner and instructor with the Orthopaedic Division of the Canadian Physiotherapy Association.
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domain: health


After months of BIOS firmware updates and software patches, both platforms from Intel and AMD should have reached some level of maturity by now. We run a myraid of tests with HD 7970 GHz Edition CrossfireX and G.Skill 16GB 2400MHz ram to see how everything goes at 4.6GHz."
Any major computer upgrade generally requires a full software reinstall too. No so if you heed the advice in the guide to Upgrading a Motherboard without Reinstalling. PCSTATS Tips


SLS180 SLS180--THERMOSTAT AUTO RESET
The SLS series of 1/2" bimetal temperature controls offers proven reliability in a compact, versatile, cost-effective design.
- Offered in a broad temperature range to cover most heating applications
- Auto and manual reset
- UL® recognized
- CSA approved
SpecificationsDifferential °: 40 °F
Cut in temp ( °F): 140 °F
Cut out temp ( °F): 180 °F
Terminals: 45° angle ¼"


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Elephant MountainThe Youngbloods
Well, this was a strange one. A bit folky. A bit rocky. A bit jazzy. A bit country. A bit too averagey. Nothing stood out for me, and there was nothing to get my teeth into. It flowed over me like water over a rock. And left me just as cold.


4. HISTORY REPORTS}
5. GRAPHICAL REPORTS
6. COST REPORTS
7. WAITING (DEALY) ANALYSIS
Infobase Systemms was started 5 years back for software development and services to industrial need. It was found that the maintenance system is not computerised in many industries. Even in the companies where maintenance is computerised, the software is not good enough to provide useful information. Hence we developed CMMS software COMPAC.
COMPAC is one of our most exalted product and it has proved its quality with its influential maintenance reports in many prestigious companies in India.
COMPAC software was developed by a group of experienced maintenance personnel who have wide experience in different types of industries. This soft can be put into use within few days, and useful maintenance reports can be generated immediately. This software is very simple to use as codification of machines, breakdowns causes and remedial actions have been avoided.
Your company will be able to reduce many unexpected breakdowns and optimise Preventive Maintenance activities with the help of our COMPAC software. It will result in savings to your company, much more than the price of our COMPAC software. We are sure that implementation of our COMPAC software in your plant will definitely have a great effect in bringing trouble free maintenance
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Spina bifida myelomeningocele myelomeningocele is a severe type of spina bifida in which the membranes and the spinal nerves protrude at birth forming a sac on the baby s back. This is the most severe type of spina bifida.
The exposed nervous system may become infected so prompt surgery is needed after birth.
Spina bifida myelomeningocele definition. It happens when parts of the spinal cord and nerves come through the open part of the spine. Medical definition of myelomeningocele. Meningomyelocele also commonly known as myelomeningocele is a type of spina bifida.
Spina bifida and myelomeningocele spina bifida and myelomeningocele spina bifida latin for split spine is a type of neural tube defect which is a problem with the spinal cord or the structures that cover it. With this condition a sac of fluid comes through an opening in the baby s back. When people talk about spina bifida most often they are referring to myelomeningocele.
Myelomeningocele is a sacculation of the meninx and spinal cord through a vertebral defect that develops because of a closure defect of the posterior neuropore which is the latest phase of neurulation in the third and fourth weeks of gestation. Here the baby s spinal canal is open in one or several places in the lower or middle back and a sac of fluid pokes out. Spina bifida in which neural tissue of the spinal cord and the investing meninges protrude from the spinal column forming a sac under the skin learn more about myelomeningocele.
Myelomeningocele is the most severe form of spina bifida. It causes nerve damage and other disabilities. Myelomeningocele mmc also known as meningomyelocele is the type of spina bifida that often results in the most severe complications and affects the meninges and nerves.
Spina bifida is a birth defect in which the spinal canal and the backbone don t close before the baby is born. In individuals with myelomeningocele the unfused portion of the spinal column allows the spinal cord to protrude through an opening. Part of the spinal cord and nerves are in this sac and are damaged.
Seventy to ninety percent of children with this condition also have too much fluid on their brains hydrocephalus. Myelomeningocele is the most serious type of spina bifida.

domain: medical


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Reyes Highlights Quiet Group
There wasn’t a lot of money in the United Rotisserie League signings on Friday, but there was a top-10 contract signed as shortstop Jose Reyes agreed to a five-year, $305 deal with the Texas Outlaws.
Texas, which has signed the fewest players of any of the eight teams, was glad to close the deal on Reyes, according to owner Robert Arnwine.
“He brings everything to the table–hitting for average, hitting for power, speed. He’s going to be a cornerstone in Texas for a long time to come,” said Arnwine.
Elsewhere in the signings, the Atkins Alley Cats signed a total of six players, while every other team inked one player save the Arkansas Cardinals, who were shut out in the signing process for the second straight group.
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domain: news


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NCI Dictionary of Cancer Terms
The NCI Dictionary of Cancer Terms features 8,525 terms related to cancer and medicine.
We offer a widget that you can add to your website to let users look up cancer-related terms. Get NCI’s Dictionary of Cancer Terms Widget.
- APC vaccine
- listen (… vak-SEEN)
- A vaccine made of antigens and antigen-presenting cells (APCs). APCs boost an immune response by presenting antigens on their surfaces to other cells of the immune system. Also called antigen-presenting cell vaccine.


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Topical nasal decongestants
Drug safety update
Inhalation of warm moist air is useful in the treatment of symptoms of acute infective conditions.
Sympathomimetics are likely to cause rebound congestion and are of limited value. They are available from pharmacies over the counter at a cost less than a prescription charge. They should be used for short periods of time only (usually not longer than 7 days). The CHM/MHRA advise that these medicines should not be used in children under 6 years of age.
Ephredrine nasal drops are the safest sympathomimetic preparation. Xylometazoline, altough more potent, is more likely to cause rebound congestion.
Sodium chloride 0.9% nasal drops may relieve nasal congestion by helping to liquify mucous secretions.
Orally administered nasal decongestants may not be as effective as preparations for local application but they do not give rise to rebound nasal congestion on withdrawal.
Caution: diabetes, hypertension, hyperthyroidism, raised intraocular pressure, prostate hypertrophy, hepatic impairment, renal impairment and ischaemic heart disease and avoid in patients taking monoamine oxidase inhibitors (MAOIs).
Likely to be of limited value and more likely to cause rebound congestion


The Colorado Buffaloes didn’t miss Tyler Bey, as the junior forward missed the first game of his career in CU’s 78-56 win against Washington State Thursday night.
Bey’s absence would be much more ominous on Saturday against a Washington frontcourt that features a pair of possible NBA-bound freshmen forwards in Jaden McDaniels and Isaiah Stewart. However, Bey’s absence isn’t expected to be an extended one.
Following Thursday’s win, CU head coach Tad Boyle reported that Bey, who was in uniform but remained on the bench with a bandage covering a portion of his right hand, suffered an injury during practice this week. After playing in 86 career games with 75 consecutive starts, Bey is expected to be back in the lineup on Saturday against the Huskies at the CU Events Center (7 p.m., FS1) .
“Tyler could have played tonight,” Boyle said. “He had an injury in practice. He didn’t practice on Tuesday. Very, very limited yesterday (Wednesday). I just felt like if we could get through this game, I don’t want him to re-aggravate it. But he’ll be ready to go on Saturday. It’s something we’ll monitor.
“With any injury, if it’s not right up here (points to head), it ain’t right. So we need to get it right up here. And it wasn’t right up here today. So we tried to make it through without him and we did. Hopefully Saturday we’ll have him back. I expect to.”
The 10 assists posted by McKinley Wright IV against Washington State secured a few more milestones for CU’s junior point guard.
That total increased Wright’s career assist total to 442, moving him past Jose Winston for third-place on CU’s all-time list. Next up is Mike Reid with 446 assists, followed by all-time leader Jay Humphries at 562.
It was Wright’s ninth career double-double overall and his seventh in points and assists, breaking a tie with Humphries for the most points-assists double-doubles in program history. Wright also tied Humphries’ team record with the seventh double-digit assist total of his career.
Wright also tied a career-high against WSU with three blocked shots.
The Buffs posted three double-doubles in a game for the first time since a home win against Colorado State last season. On Thursday it was Lucas Siewert (16 points, 10 rebounds), Wright (10 points, 10 assists), and Evan Battey (12 points, 10 rebounds). Last year against CSU it was Siewert (16 points, 10 rebounds), Wright (18 points, 11 assists), and Bey (23 points, 10 rebounds)…Siewert made three 3-pointers to increase his career total to 121 and move past Chauncey Billups for 14th-place all-time at CU…It was the eighth time this season the Buffs have held the opposition under 60 points…The Buffs’ 19 assists was their second-highest total of the season, trailing only the 26 they recorded against Iona on Dec. 29.


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Capturing those perfect moments with just the Bride & Groom is my all-time favourite part of a Wedding. It takes time, experience and a lot of skill to perfect portraiture in photography and my approach has always been to capture natural & creative photographs of the Bride & Groom.
Each week I will share one of my Wedding Images, sharing my tips on posing, how to encourage the couple with feedback and prompts and give an overview of my camera settings.
Remember that each Wedding is different, I have a handful of posing ideas I use, each pose can lead to something different and unique. Capturing a perfect portrait is not always about posing, asking the Bride and Groom to kiss can lead to genuine laughter, that moment can create some of the best photographs of the day.
Living in the United Kingdom there is a good chance you may expect rain on a Wedding Day. I always discuss with the Bride & Groom potential weather scenarios a long time before the Wedding Day arrives. If it rains on a couple's big day, it is part of their story, I never try and hide the fact it rained but instead use it to my advantage. 99% of the Bride & Grooms I capture are totally fine with the possibility of it raining during their Wedding day because we have discussed the situation prior and after all the day will still be amazing regardless of the weather!
On this occasion Vicky & her Bridesmaids were more than happy to step outside for some group shots. When shooting a bride with her bridesmaids, ask the Bridesmaids to gather around the bride for a tight and fun shot. Vary the poses between them all and ask a few of them to turn for variation. Use open suggestions such as asking for their 'signature/ go to' pose. Bridesmaids are always more than happy to help create some awesome shots on the bride's wedding day, suggesting they do something different or humorous allows them all to show a little bit about their individual personality.
Make sure you give plenty of feedback and praise, consider saying something funny to capture some laughter. If the wedding party feel comfortable around you they will not only feel comfortable around you all day, but they're more likely to recommend you or even book you for their wedding in the future.
Have you had any experience of shooting weddings in the rain? Do you have any useful tips for posing group shots?


Folding Alpha Hunter Knife - The perfect balance of weight and design give this knife the smoothest one-handed manual action on the market. Offered with Rubberized scales and 420HC Satin Finish blade. Made in the USA - Blade Shape: Drop Point - Blade Length: 3 1/2 (8.9 cm) - Weight: 8 oz. (227.8 g) - Handle: Rubber - Carry System: Sheath - Origin: Made in the USA
Determined at checkout.


Rappler's latest stories on identity
Officials in the eastern province of Shandong say a two-year investigation had found more than 280 people involved in stealing the identities of students sitting the 'gaokao,' or Chinese university entrance exams
'Believe it or not, 'Mission Unstapabol' is a refreshing effort from Tuviera, Sotto and their usual team.'
Vic Sotto says MMFF entry 'Mission Unstapabol: The Don Identity' 'definitely different' from past movies
'Gusto ko naman kasi paglabas nila ng sinehan may mga ngiti sa kanilang mga mukha,' Vic says
Senate President Vicente Sotto III says more than half of senators are against the SOGIE equality bill, but Senator Risa Hontiveros believes the measure has a 'strong fighting chance'
I believe that the Philippines is still a country with a purpose, a country with a bright future. We are slowly letting go of our ways that did not work for us in the past.
The Israel president says: 'I have a directive: no intelligence connection in the United States, no spying... It's rigorously enforced without any exception'
Rappler talks to Senator Risa Hontiveros, lead author of the SOGIE equality bill at the Senate, on how she plans to fight misinformation on the measure
Amid heated discussions on the SOGIE equality bill, a group of LGBTQ+ advocates and allies explore the power of empathy through proactive education
Is the Philippines an LGBT-friendly country? There is little acceptance in places where it matters the most: in schools, in government, and among families.
The bill seeks anti-discrimination on the basis of SOGIE, not infringement on religious liberties or parental authority
Koko Alviar of the Aglipayan Church says his faith teaches him to 'exist in a community of love.' Coalition of Concerned Families of the Philippines lawyer Lyndon Caña argues that gender identity is a mere 'feeling' and not a fact.
Senate President Vicente Sotto III maintains that the SOGIE equality bill, in its current form, is not likely to get enough support in the Senate
Watch the Senate hearing on the SOGIE equality bill live on Rappler
Anti-discrimination laws aid in protecting members of the LGBTQ+ community as it strives towards achieving equality for all
'What happens to a Christian like me...if we are to be threatened by punishment every time we share our Bible-based beliefs on matters of transgenders and homosexuals?' asks Brother Eddie Villanueva
The fight for equality and anti-discrimination for the LGBTQ+ community is one that has known almost two decades of legal struggle
Most Philippine companies cannot be said to be LGBTQ+-friendly
(UPDATED) Senate President Vicente Sotto III says the SOGIE equality bill stands no chance if 'it transgresses on academic freedom, religious freedom, and women’s rights'
We talk to Mela Habijan about terms, definitions, and why recognition matters
‘Mister President, naumpisahan na natin. Sana ipagpatuloy na natin ang pagpapasa sa SOGIE equality bill,’ says Gretchen Diez
In this video, we explain how SOGIE can be mixed and matched in many ways
'Ipasa na natin ang SOGIE equality bill. Para kay Gretchen [at] sa lahat ng Filipino lesbians, gays, transgenders, intersex, queers, at asexuals, na matagal nang nakaposas sa...diskriminasyon,' says Senator Risa Hontiveros
'Why not just Homo sapiens? We’re all the same,' remarks Senate President Vicente Sotto III
(UPDATED) The Trade Union Congress of the Philippines and Sentro make the call after the arrest of transgender woman Gretchen Custodio Diez at a Quezon City mall
Gender is often confusing for a lot of people. In this video we explore the concept of SOGIE.
As to how long the light will stay will all depend on the sterling commitment of people to fight for the beautiful cause of the rights of LGBTIQ persons
These are the films that are part of this year's 'Magic 8'
'Identities are never fixed.... Pride Marches should present messy spaces that constantly evolve,' says sociology professor Evangelista
President Rodrigo Duterte's enduring popularity is baffling. What are the factors that might explain it?
Six out of 10 members of the LGBT+ community experience outright injustice
'Over a quarter of a million Rohingya refugees from Myanmar have now been jointly registered and provided with identity cards by Bangladesh authorities and UNHCR,' spokesman Andrej Mahecic tells reporters in Geneva
‘Other issues might take precedence over this, but that doesn’t mean we can’t push for it…. All rights are important,’ Cogencia chief executive officer Paulo Edrosolano says
'There is a misconception that the bill goes against our religious beliefs, our religious freedom, but that is far from the truth,' says Pia
I make this appeal for the sake of science, for the sake of morality and for the sake of the nation’s well-being
The latest victory for the LGBT community leaves just 3 US states that prohibit amending the gender marker on the official identification documents: Kansas, Ohio and Tennessee
Here are the stories you shouldn't miss this Friday
Portugal becomes 'the 6th European country to grant the right to self-determination of transgender identity... without the guardianship of a third party and without a diagnosis of identity disruption'
(UPDATED) 'I believe that it’s about time to rise together against discrimination, exclusion, and violence,' says Mindanao Pride founder, Hamilcar Chanjueco
Senate Majority Leader Vicente Sotto III, a conservative, says the bill is practically dead in the 17th Congress
‘Black Panther’ sends an empowering message on postcolonialism
'I do my best to use this privilege and power to contribute back to Filipino society. I’m incredibly proud to be Filipino. Manila may be melty and monstrous, but I love it.'
The National Bureau of Investigation is tasked to conduct the probe, and file appropriate charges
The fake account contains a picture of Uy in his priestly garb as the profile photo and a picture of him with a group of nuns as the background image. The fake account is reportedly soliciting donations in his name.
(UPDATED) Germany is the 15th European nation to legalize gay marriage, but advocates say the battle for equal rights continues
Jayross 'Utoy' Brondial, 13, is killed by a motorcycle-riding, masked gunman, whom neighbors believe was after another neighbor – Gary 'Gayi' Alandra, who is on top of the barangay drug watch list
The police accuse Willyn Trabajador of posting a bomb threat against President Rodrigo Duterte, but the criminal complaint they filed against her raises more questions than answers
EXCLUSIVE: The Philippine National Police files a criminal complaint against Willyn Trabajador, whom they accuse of posting a bomb threat against the President's followers. But Trabajador insists her account was cloned.
This is the farthest the bill has gone in the legislative process since it passed on 3rd and final reading during the 11th Congress
Becoming Maranao for me was more than having Maranao parents and being raised in a Maranao family
Representatives Emmeline Aglipay Villar Kaka Bag ao and Geraldine Roman sponsor the proposed SOGIE Equality Act for 2nd reading in the House


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ASC contracts with MeriStar
Failed merger partner to oversee Steamboat Grand
Steamboat Springs — The planned merger between American Skiing Co. and MeriStar Hotels and Resorts was withdrawn in March. But the two companies have decided to work together anyway.
American Skiing, parent of the Steamboat Ski Area, announced Tuesday it had assigned a management consulting contract with MeriStar to oversee operations of its lodging properties. American Skiing will continue to own the properties and its reservations networks. The hotel and condominium managers and staff will continue as employees of American Skiing Co. resorts.
The announcement comes five months after a merger between the two companies fell apart, due largely to a lack of encouragement from Wall Street. Former ASC chairman Les Otten announced the intent to merge in December 2000. He resigned his post five days after the merger was withdrawn.
The timing of the announcement also comes as ASC is hoping to identify a buyer for the Steamboat Ski Area. Company officials have said the sale of Steamboat might or might not include the Steamboat Grand Hotel.
Steamboat Grand Manager Terry Murphy said it’s difficult to predict at this point what this might mean for his hotel.
“In the event the Grand is not sold and stays within the realm of American Skiing Co., the relationship with MeriStar would continue in Steamboat,” Murphy said. “We’d have the opportunity to have a professional hotel management company help support the hotel.”
Murphy worked closely with MeriStar officials for four months while the merger was pending. He said was looking forward to the relationship then and would look forward to a future relationship, albeit of a different nature, if things work out that way.
Depending upon whom the buyer of the ski area is, if they also purchased the hotel, they might choose to piggyback on the MeriStar relationship, Murphy theorized. But he said he wouldn’t really know anything until the prospective buyer of the ski area is announced, perhaps in September, and the terms of the deal are revealed.
MeriStar claims to be the nation’s largest independent hotel management company. It has contracts to manage hotels bearing a wide variety of flags all over the country.
Most of the MeriStar-managed hotels are in warm-weather climates, and Otten hoped the merger would offer American Skiing a more consistent source of year-round revenue that wasn’t as dependent upon the weather as ASC’s ski resort hotels.
American Skiing doesn’t stand to gain new revenue streams as a result of its agreement to consult with MeriStar.
However, CEO B.J. Fair said his company’s resort would benefit from the installation of MeriStar’s controls and procedures at its eight Grand Summit Resort Hotels.
“MeriStar has an outstanding approach to hotel and resort lodging operations,” Fair said in a prepared statement. “This arrangement reflects our commitment to ensuring we can deliver the highest quality experience and services to our guest.”
Had the merger between American Skiing and MeriStar been consummated, the new company, Doral International, would have owned or managed nine ski resorts, 23 resort hotels, 246 other hotels, 15 golf course and four conference facilities.
American Skiing plans to sell Steamboat as part of a financial reorganization intended to alleviate the company’s stifling debt load.
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There were a lot of new laptops, updates, and more at CES 2022, and many of them came out at the show.
We saw a few big trends when we looked at the best new laptops from Dell, HP, Lenovo, and Asus. These trends will be important for laptops in 2022 and beyond.
Haptic Trackpads Are Here To Stay
Apple has made haptic feedback trackpads for a long time. As opposed to using a physical button, the trackpad uses motorized haptics to replicate the sensation of a click without the need for a real button. After years of only having the technology on MacBooks, we started to see high-end Windows laptops like the Surface Laptop Studio use it in 2021, after years of only having it on MacBooks
But at CES 2022, it looks like it’s a full-blown trend. As soon as we saw it, Dell’s XPS 13 Plus laptop had a trackpad built into the glass on the palm rests. It also showed up in the ThinkPad Z13, another new laptop that caught our eye at CES.
You might not expect to find this kind of trackpad on the HP Elite Dragonfly Chromebook, but it did. Now, this isn’t just any old Chromebook. It might be the best-looking Chrome OS device ever made. That said, this technology is spreading so quickly shows that it’s becoming more common.
There Is No Longer Any Place For 720p Webcams.
The webcams were everywhere you looked at this year’s CES, and that’s because they were so important. It took more than two years, but laptop manufacturers finally made the slow gears of supply chains move in response to the rise of working from home and other places where people can’t be there. A webcam of at least 1080p was found on almost all of the new laptops shown at this year’s CES trade show. HP even made it a point to put a 5-megapixel camera in every commercial PC that was made.
Even most of the monitors shown at CES had built-in webcams, even though they didn’t show up there. Even new high-end laptops like Dell’s UltraSharp U3223QZ or HP’s Z34c have 4K cameras on top for crystal-clear video calls. It means you can see everything clearly when you talk on the phone.
If you bought a new tech product in 2021, it would likely have a better webcam than in the past. How wonderful!
OLEDs and Mini-LEDs May Be Found Just About Wherever These Days.
Conventional LED was the only option for laptop screens for a long time. In fact, at CES 2022, it became clear that laptops with newer display technologies are finally making their way into many of them. The OLED and mini-LED technology were all over the place at CES. You could see it in big monitors, gaming laptops, and normal Ultrabooks.
Heck, we even saw the new QD-OLED panel in a gaming monitor, the Alienware 34 QD-OLED, as soon as the first Samsung TVs came out with the new panel. I think that’s great, and it shows that manufacturers are finally paying attention to the technology behind the screen.
New Graphics Options
There is no doubt that Nvidia is the best at making computer games look good on a computer. But Intel and AMD showed up at CES 2022 to show a real alternative. AMD added more to its Radeon 6000 series with eight new mobile GPUs. There are options for thin and light gaming laptops to fight Nvidia’s Max-Q technology. They also showed impressive graphics abilities in their new Ryzen 6000 chips, which have built-in APUs.
On the other hand, Intel announced a soft launch of its first Arc Graphics. People who like to play games and do things with a lot of power will like these Intel GPUs. There are a lot of unknowns about Intel Arc, but over 50 PCs, both desktops and laptops, are said to be coming out with the new graphics. That’s a good start for a company that wants to get into the discrete GPU market.
However, no matter what kind of computer you buy, there are more graphics options than ever before. RTX 3080 Ti and 3070 Ti from Nvidia are safe bets.


|  Sharma S. Expanded cloud plumes hiding big data ecosystem. Future Generation Computer Systems, 2016, 59:63-92. Yu Y, Ni J B, Man H A, Mu Y, Wang B Y, Li H. Comments on a public auditing mechanism for shared cloud data service. IEEE Trans. Services Computing, 2015, 8(6):998-999. Kandukuri B R, Ramakrishna P V, Rakshit A. Cloud security issues. In Proc. IEEE International Conference on Services Computing (SCC), September 2009, pp.517-520. Stinson D R. An explication of secret sharing schemes. Designs, Codes and Cryptography, 1992, 2(4):357-390. Beimel A. Secret-sharing schemes:A survey. In Coding and Cryptology, Chee Y M, Guo Z B, Ling S, Shao F J, Tang Y S, Wang H X, Xing C P (eds.), Springer, 2011, pp.11-46. Peng K. Critical survey of existing publicly verifiable secret sharing schemes. IET Information Security, 2012, 6(4):249-257. Maheshwari N, Kiyawat K. Structural framing of protocol for secure multiparty cloud computation. In Proc. the 5th Asia Modelling Symp. (AMS), July 2011, pp.187-192. Hamari J, Sjöklint M, Ukkonen A. The sharing economy:Why people participate in collaborative consumption. Journal of the Association for Information Science and Technology, 2016, 67(9):2047-2059. Shamir A. How to share a secret. Communications of the ACM, 1979, 22(11):612-613. Blakley G R. Safeguarding cryptographic keys. In Proc. AFIPS 1979 National Computer Conf., June 1979, pp.313-317. Antonopoulos A M. Mastering Bitcoin:Unlocking Digital Crypto-Currencies. O'Reilly Media, 2014. Rivest R, Shamir A, Adleman L M. A method for obtaining digital signatures and public-key cryptosystems. Communications of the ACM, 1978, 26(2):96-99. Paillier P. Public-key cryptosystems based on composite degree residuosity classes. In Advances in Cryptology, Stern J (ed.), Springer, 1999, pp.223-238. Lindell Y, Pinkas B. Privacy preserving data mining. Journal of Cryptology, 2002, 15(3):177-206. Gaetani E, Aniello L, Baldoni R, Lombardi F, Margheri A, Sassone V. Blockchain-based database to ensure data integrity in cloud computing environments. In Proc. the 1st International Italian Conference on Cybersecurity, January 2017, pp.146-155. Ali M, Nelson J, Shea R, Freedman R J. Blockstack:A global naming and storage system secured by blockchains. In Proc. USENIX Annu. Technical Conf. (ACT), June 2016, pp.181-194. Liang X P, Shetty S, Tosh D, Kamhoua C, Kwiat K, Njilla L. ProvChain:A blockchain-based data provenance architecture in cloud environment with enhanced privacy and availability. In Proc. the 17th IEEE/ACM International Symposium on Cluster Cloud and Grid Computing (CCGRID), May 2017, pp.468-477. Cai C J, Yuan X L, Wang C. Towards trustworthy and private keyword search in encrypted decentralized storage. In Proc. IEEE International Conference on Communications (ICC), May 2017. Miller A, Juels A, Shi E, Parno B, Katz J. Permacoin:Repurposing bitcoin work for data preservation. In Proc. IEEE Symp. Security and Privacy (SP), May 2014, pp.475-490. Frikken K B. Secure multiparty computation. In Algorithms and Theory of Computation Handbook, Atallah M J (ed.), Chapman and Hall/CRC, 2010. Fouque P A, Poupard G, Stern J. Sharing decryption in the context of voting or lotteries. In Financial Cryptography, Frankel Y (ed.), Springer, 2000, pp.90-104. Baudron O, Fouque P A, Pointcheval D, Stern J, Poupard G. Practical multi-candidate election system. In Proc. the 20th Annu. ACM Symp. Principles of Distributed Computing (PODC), August 2001, pp.274-283.


BATON ROUGE, La. -- LSU smashes four home run in 16-1 win over Southern Wednesday night at Alex Box Stadium, Skip Bertman Field.
The Tigers remain at home this weekend as they take on Oral Roberts University.
Will Hellmers (2-0) records the victory, his second of the year. Southern's Daren Smith (0-1) is charged with the loss.


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Howl’s Kitchen Canine Cookies Antioxidant Formula are irresistible dog treats made with real chicken and antioxidant-rich cranberries. These tasty, crunchy snacks also help reduce plaque and tartar on your dog’s teeth, and are made with no wheat, corn, soy, artificial colors or flavors, or preservatives!
- Made with real chicken and cranberries
- Chewing helps reduce plaque and tartar
- No artificial colors, preservatives, or flavors
- No corn, wheat, or soy
Made in the USA.
Feeding Guide: Fresh baked Canine Cookies are perfect treats for any time of the day. They’re great as rewards, training treats, or a yummy snack.
Ingredients: Barley Flour, Ground Peas, Brown Rice, Chicken Meal (source of Glucosamine and Chondroitin), Chicken Fat (preserved with Mixed Tocopherols), Chicken, Cranberries, Salt, Calcium Carbonate, Powdered Cellulose, Spinach, Natural Chicken Flavor, Vitamin E Supplement, Vitamin C Supplement, Minerals (Zinc Sulfate, Copper Sulfate, Manganese Sulfate, Calcium Iodate, Sodium Selenite), Rosemary Extract, Vitamin A Supplement.
Crude Protein (min) – 17.0%
Crude Fat (min) – 5.0%
Crude Fiber (max) – 5.0%
Moisture (max) – 12.0%
Calcium (min) – 1.0%
Zinc (min) – 125 mg/kg
Vit. A (min) – 4,500 IU/kg
Vit. E (min) – 500 IU/kg
Vit. C (min) – 450 IU/kg
Calories – 20 kcal/treat

domain: food


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Enjoy with Xylophone Piano for Kids. It’s the musical instrument anyone can play
This game is a free xylophone for your smart phone or tablet pc!
You can use this xylophone to learn the basics of music.
Xylophone instrument is a fun musical instrument anyone can play!
– Realistic and soft sounds
– HD graphics and funny design
– Supports all screen resolutions for mobil devices
The second level of the game is balloon pop game with funny characters. You will enjoy pop the balloons.


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Tofino council has unanimously put its support behind an initiative to have Mackenzie Beach renamed to its traditional Indigenous name.
In September, the Tla-o-qui-aht First Nation launched a petition to have the B.C. government recognize Mackenzie Beach as tinwis, which means “calm waters.”
As of Saturday, the petition has received more than 2,100 signatures, nearing its 2,500 goal.
At a council meeting Tuesday, the District of Tofino approved a motion to “support the TFN’s (Tla-o-qui-aht First Nation) initiative to change the name of Mackenzie Beach to tinwis.”
The move comes about a year after the District of Saanich restored the Indigenous name of PKOLS to Mount Douglas Park.
Around the same time, the Haida Gwaii village of Queen Charlotte was also renamed to its historical First Nations name of Daajing Giids.

domain: geography


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Hailey Bieber home and recovering after recent hospitalization in Palm Springs
Hailey Bieber is home and recovering from a recent health scare that took place in Palm Springs last week, according to PEOPLE magazine.
The 25-year-old model, who is also the wife of popstar Justin Bieber, was admitted to a hospital Thursday in Palm Springs with stroke-like symptoms caused by a blood clot in her brain, she shared in a statement on Saturday.
Not outlet was able to confirm which desert hospital Bieber was treated at.
"On Thursday morning, I was sitting at breakfast with my husband when I started having stroke like symptoms and was taken to the hospital," she wrote
Bieber said her body was able to pass the clot on its own and she recovered in a few hours.
"Although this was definitely one of the scariest moments I've ever been through, I'm home now and doing well, and I'm so grateful and thankful to all the amazing doctors and nurses who took care of me," she wrote. "Thank you to everyone who has reached out with well wishes and concern."
USA Today reached out to Bieber's reps for additional information.
Bieber has been open about her health struggles in the past, including her mental health and the health of her husband. In Elle's March 2020 issue, Bieber opened up about how her partner's struggle with Lyme disease affected their marriage.
USA TODAY celebrity reporter Elise Brisco contributed to this report.

domain: celebrity


Detroit Red Wings prospect Dmitri Buchelnikov was recently mentioned as a potential KHL Rookie of the Year contender for the upcoming season.
Buchelnikov, 19, was selected 52nd overall in the second round by the Detroit Red Wings in the 2022 NHL Entry Level Draft. This past season, the 5-foot-10 winger appeared in ten games for St. Petersburg SKA of the KHL, where he recorded one goal and two points. He was also a plus-2 in limited duty.
The Russian winger may be overlooked by some Red Wings’ fans simply due to the fact that Marco Kasper headlined the 2022 draft for Detroit, and we got a small glimpse of the young center last season. Kasper played in one game with Detroit in Toronto late last season before being shut down due to injury. Kasper is expected to spend the upcoming season in Grand Rapids with the Griffins, while Buchelnikov will play his first full professional season in the KHL. Kasper is expected to grow into a ‘do-it-all’ center for the Detroit Red Wings, and Buchelnikov is projected to be a scoring winger.
"“Even before the start of the 2022/2023 season, Dmitri Buchelnikov was one of the main contenders for a breakthrough among young KHL players,” writes Anton Vasyatin on KHL.ru.“The next logical stage of a career should be the KHL, and on an ongoing basis,” Vasyatin notes. “Regardless of whether it happens in SKA or in another club (if the leadership of the army team prefers a lease)."
Detroit Red Wings prospect Dmitri Buchelnikov has big-time scoring potential.
Buchelnikov spent the majority of last season playing for SKA’s junior squad, Russia’s minor league level, or the American Hockey League equivalent. He totaled 15 goals and 13 assists in 35 contests with the junior clubs. Before that, Buchelnikov put up impressive numbers, with the Russian under-17 team recording a whopping 61 points in 28 games during the 2019-20 campaign. He’d follow that up the next season with eye-popping numbers, scoring 41 goals and adding 34 assists in the MHL.
Buchelnikov is under contract with St. Petersburg SKA through the 2025 season, so it may be a while before we see him in North America. There is a benefit, though. If all goes well, he will spend the next couple of seasons developing in Russia’s top professional league, playing against primarily established players.
Translation: When/if he does arrive in North America in the summer of 2025, he should hit the ground running and possibly begin his career within the organization right at the NHL level. It’s not for sure, as there will always be an adjustment for any player entering the NHL, but certainly a chance.


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I installed a DC PD (Thorlabs PDA 520) in the beam path to AS55. I placed a 2" 90/10 BS on a flip mount that picks of enough light for the PD to spit out ~8V when the port is bright. Single arm continuous signal will be ~2V. While most of the light still continues towards AS55, the displacement from the BS moves the beam off AS55, so I used the flip mount in case anyone needs to use AS55. The current configuration is UP.
When we're done with loss investigations the flip mount should be removed from the bench.
I hooked the PD up to an ethernet-enabled scope and started scripting the loss map measurement (scope can receive commands via http so we can automate the data acquisition). The scope that was present at the bench and had been used for the MC ringdown measurements had a 'scrambled' screen that I couldn't fix so I had to retrieve another scope ("scope1"). I'll try to find out what's wrong with it but we may have to send it in for repair.
I made a crude sketch for how Lydia and I envision the connector situation on the back of the vme crates to be solved. Essentially the side panels of each crate extend about 2" (52 mm) beyond the edge of the DIN connectors. This is plenty of space for a simple PCB board. The connector of choice is D-Sub. We can split the 64 used pins into 2x 37 D-Sub OR (2x25 pin + 1x15pin). The former has fewer cables, but a few excess unused leads. A quick google search showed me that it is much cheaper to get twisted pair cables for 15 and 25 pin D-Subs. From what I remember, the used pins on the DIN connectors are concentrated on the low numbers end and the high numbers end, so might not need the 'middle' connector in many cases if we decide to break it up into three. I have to check this with Lydia though.
The D-Sub connectors would be panel mounted, for which we need a narrow panel piece with dsub cutouts. We can run horizontal struts across the vme crate from side panel to side panel. This way the force upon cable (dis)connection is mostly on the panel which is attached to the struts which are attached to the crate. This will also prevent gravitational sag or cable strain from pulling on the DIN connection, and we can use twisted pair cables with backshell, screws, and strain reliefs.
I was lookng into getting started with the PCB when Altium complained that the license is expired and to renew it. This is a relatively simple board layout so some free software out there is probably enough.
After fighting with Altium for what seems like an eternity I have finished putting my vision of the vme crate backplane adapter board into an electronic format. It is dimensioned to fill the back space of the crate exactly. The connectors are panel mount and the PCB attaches to the connectors with screws, such that the whole thing will be mechanically much more stable than the current configuration. A mounting bracket will attach to horizontal struts that need to be installed in the crates, mechanical drawings to follow.
I finished designing the PCBs for the VME crate back sides (see attached). The project files live on the DCC now at https://dcc.ligo.org/LIGO-D1700058. I ordered a prototype quantity (9) of the PCB printed and bought the corresponding connectors, all will arrive within the next two weeks. See also attached the front panels for the Acromag DAQ chassis and Lydia's RF amplifier unit (the lone +24V slot confuses me: I don't see a ground connector?). On the Acromag panel, six (3x2) of the DB37 connectors are reserved for VME hardware, two are reserve, and I filled the remaining space with general purpose BNC connectors for whatever comes up.
Just a few remarks, since I heard from Gautam that c1susaux is next in line for upgrade.
All units have already been configured with IP addresses and settings following the scheme explained on the slow controls wiki page. I did this while powering the units in the chassis, so I'm not sure where the short is coming from. Is the power supply maybe not sourcing enough current? Powering all units at the same time takes significant current, something like >1.5 Amps if I remember correctly. These are the IPs I assigned before I left:
I used black/white twisted-pair wires for A/D, red/white for D/A, and green/white for BIO channels. I found it easiest to remove the blue terminal blocks from the Acromag units for doing the majority of the wiring, but wasn't able to finish it. I had also done the analog channel calibrations using the windows untility using multimeters and one of the precision voltage sources I had brought over from the Bridge labs, but it's probably a good idea to check it and correct if necessary. I also recommend to check that the existing wiring particularly for MC1 and MC2 is correct, as I had swapped their order in the channel assignment in the past.
While looking through the database files I noticed two glaring mistakes which I fixed:

domain: design


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I am always looking for fun small places to eat.
I have also lately been trying to venture out and eat other international cuisines besides Mexican and Italian. After having amazing Thai food with my mother I figure I would give a local Plano, Texas Thai place a go.
I went to Jasmine Thai Cuisine and it was fantastic.
I had the Thai Basil Fried Rice. Seriously give it a go it was fantastic
If you find yourself in Plano and craving Thai swing by
Jasmine Thai Cuisine
1116 W. Parker Rd
Plano TX 75075
If you are lucky like me and work within 5 miles they deliver.


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Matilda Sissieretta Joyner Jones (1868-1933) African-American soprano sometimes called "The Black Patti" in reference to Italian opera singer Adelina Patti. In June 1892, Jones became the first African-American to sing at the Music Hall in New York (Now known as Carnegie Hall.) Touring internationally in the late 1800s and early 1900s, she sang both classical opera and performed in musical comedies with her own troupe. Photo taken 1889.
Leontyne Price (born 1927) by Bradley Phillips (1929-1991).Regardless of their talents, African American singers were for years generally barred from performing with this country's more prestigious opera companies. In 1952, when audiences experienced the rich voice of Mississippi-born soprano Leontyne Price in a revival of Porgy and Bess, it became clear that this long-standing barrier would soon be breached.

domain: entertainment


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Deleted scene from the upcoming documentary where Sam Harris makes the distinction between the common problem of bad ideas and the rare problem of bad people. Islam and the Future of Tolerance available worldwide on December 11th.
Kay Nielsen – Fairy TaleKay Rasmus Nielsen (March 12, 1886 – June 21, 1957) was a Danish illustrator who was popular in the early 20th century, (more…)
Art Deco styles into advertising design – Coles PhillipsClarence Coles Phillips (October 1880 – June 13, 1927) was an American artist and illustrator who signed his early works C. Coles Phillips, but after 1911 worked under the abbreviated name, Coles Phil...
Candas Sisman manipulate our notion of time, space and motion, using digital and mechanical technolo...(more…)


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About this property
Ágora is a new off plan development in a unique location close to Estepona and Marbella. This exclusive project features just 34 contemporary apartments and penthouses built in a unique peaceful location combining the beauty of nature with cutting edge architectureÁgora offers stunning new apartments which are all South facing with unobstructed views across a beautiful natural valley and protected forest area and sea views from the upper levels. All of the apartments have wide open terraces with unique wrap around pergolas and natural stone elements incorporated into the design to enhance the picturesque natural surroundings. Each floorplan has been uniquely designed to make the very most of its location. This is clearly visible with a variation of designs all centred around large, light-filled living areas that
benefit from full-width glass sliding doors. The lounge areas lead into huge terraces and the penthouse properties have an additional, incredible solarium space – perfect for entertaining. The master bedrooms are positioned towards the front of the
properties, overlooking the peaceful, natural surrounds.


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Hi everyone 🙂
On the 4th of September, we celebrate Fathers Day here in Australia. So I thought that I would get a head start by making some Fathers Day cards to share with you all.
These two cards follow the same pattern as the Tuxedo card that we made a couple of months ago, but I really liked the style and it worked really well with the Magical paper, even though its only a very small piece. The card stock that I have used is Crystal Blue with White Daisy and Slate with White Daisy.
The small piece at the neck is Champagne and this gives a nice flesh tonne to the card.
I have used a couple of red gems for the tie pins (as every card needs a little bit of bling on it). The stamp set used is from the seasonal expressions 2 catalogue, on page 23, Day for Dad C1645.
Here are the measurements and the video:
Crystal Blue card stock: 8-1/2’ x 5-1/2’ Score on the 8-1/2’ side @ 4-1/4’
White Daisy Banner pieces: 1st 4-3/8’ x 3’
2nd 4’ x 2-1/2’
Champagne neck piece: 2-1/4 x 1”
1 tie cut from magical B & T paper, the Artiste Cartridge page 75, accent 3 , cut at 4 -1/4’
- Fold and burnish the card.
- Cut the two White Daisy pieces into banners as shown.
- On top of the smaller banner cut in 1/2′. Then fold back about 1/2′ in from the edge.
- On top of the larger banner add the neck piece which is champagne.
- Attach the larger one with tape runner to the top of the card.
- Add tape runner to the smaller one and place on top of the larger one.
- Attach the tie to the top of the white banners under the collar section.
- Attach one red gem towards the bottom of the tie.
- Stamp the Happy Fathers Day in the matching ink onto a small piece of White Daisy card stock and attach to the front of the card.
Stamp set: Day for Dad C1645
Paper: Magical X7209B
Gems: Enamel Red Gems Z3090
If you have a small Happy Birthday stamp, this makes a great card for any male in your life.
I hope that you like this card and give it a go.
So till next time.
Keep on creating 😉