How does a Sony digital cybershot camera differ from Sonys other digital cameras?
Sony digital cybershots are different because they have a bigger lense and can zoom in farther and make images look better zoomed in. They also take steadier pictures.
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all sony cybershots are great, Sony alpha series best for Photography, all in all Sony is the name of quality and all its cameras are reliable. it also depends how some one finds the best Sony camera deal, smart decision always save time and cost too.
For me canon is always a better buy. On Feb 2008 I had a tour in the Himalayas (Shikim) with my Powershot A530 along with a friend with his Sony Cybershot. Both of us tried each other's camera. And what I found the CANON allows much more controls on the shots than SONY offers. See the results …here For Canon http://s128.photobucket.com/albums/p183/home_me/Gantok_Lachun_Yumthang/MukulCam/ For Sony http://s128.photobucket.com/albums/p183/home_me/Gantok_Lachun_Yumthang/AnimeshCam/. for Canon the best digital camera is CANON SX100. ANSWER 2: . I, personally like the newest canon digital cameras ( Full Answer )
Try by removing the memory stick and then attaching the camera to computer with USB cable. Switch on camera. It should open up a dialogue box in Windows XP (or similar OS). Select 'open folder to view file' or open Windows Explorer and open camera folder (probably displayed as new drive E: or like t…hat in My Computer) . You may also check whether there is an option of selecting "camera as mass storage device" in settings menu of camera. If yes then select this before connecting.. If you have no means of attaching the camera to the computer, place an empty memory stick into the camera. In review mode, a message indicates there is no data, but there is in the internal memory. While still in review mode, press the menu button and go the the "Setup" section, the last option. Now, scroll down to the "Memory Stick Tool" section. From there, highlight the "Copy" choice at the bottom, and select the OK option to proceed. You will get a message: "All data in internal memory will be copied." Press OK, and it will copy everything in the internal memory to your memory stick. Then, when you have plugged the memory stick into your computer, you will find a new folder entitled Copy. All your photos from the internal memory of the camera will be in there. ( Full Answer )
Connect the appropriate cable to USB drive from the Camera. Then open your mycomputer you will find a removable drive. Double click on the drive you will find the images in a folder.. Connect the appropriate cable to USB drive from the Camera. Then open your mycomputer you will find a removable dri…ve. Double click on the drive you will find the images in a folder. ( Full Answer )
Both are good cameras, I just tend to prefer Canons, because of there image processing. I just thing that every year they make the best point and shoots.
Most Sony consumer grade cameras use Memory Sticks. Some use both those and SD cards. SanDisk manufactures both. However, you must make sure you have the right type.
The first thing you should do is STOP using the camera to store new data which means you'd better not take more images, videos or audio etc. Then free download and install a Sony photo recovery tool on your computer to recover the deleted pictures. Note: The key success for any data recovery lies o…n those lost data are not fully overwritten. So in order to maximize chances of Sony file recovery, you should do your best to avoid that overwritten situation happens. ( Full Answer )
No, there are several different types of USB cables that fit Sony cameras, and some Sony cameras do not even have a USB port such as the DSC-P200 and some of the DSC-T series; instead they have a special cable that fits into a large port in the camera body.
The Sony cybershot camera is really good! It has many good features! It has good ratings! It is the best cheap camera anyone can have!
It likely uses a standard USB cable, though I cannot say with absolute certainty since I do not know the model of your camera. Most digital point-and-shoot and SLR cameras will transfer files via a simple USB cord.
No reason why not - connect via USB and get the computer to treat the camera as an 'external storage device' - Then you should be able to view the camera as another disk-drive (lets call it drive M) To transfer pictures to the camera - drag and drop the pics from your computers hard-drive to drive …M ( Full Answer )
The first Sony Cybershot was released in 1996. Please see that attached related link for more details.
Canon. Canon is a company focused on making great analog or digital cameras while SONY is more broad in focus.
I suggest looking for websites that sell Sony Cybershot digital cameras. When you found them on the websites look at customer reviews and see if it helps. you can also look in technology magazines that have reviews on the camera too.
A Sony Cybershot digital camera is a fantastic model of a camera by Sony. Cybershot is the model of camera that sony is most famous for. They are usually small profile cameras with incredible photo quality for their size.
Sony cybershot digital camera is set apart from other digital cameras because you can upload the pictures directly to the internet from your camera, without having to use your cord.
A sony cybershot digital camera is rather expensive for the average photographer (amateur). It will run you anywhere between $200 and $600. It is more of a camera for semi-professional photographers.
The typical price range for Sony digital cybershot cameras are between $150 to $350. The higher the price, the more options there are. However, any model Sony cybershot will take excellent pictures.
The Cybershot line is best known for its proprietary battery, called InfoLithium, and Carl Zeiss lenses. However, this line has been in existence for a very long time, so particular features are difficult to elaborate on
Which is a better option for a high school student a sony digital cybershot camera or a Kodak easyshare?
For a high school student a Kodak easyshare camera is probably better. The Sony is a great camera but it's best for taking still pictures of objects, the Kodak is much better for taking pictures of people which is what high school students generally like to do.
There are numerous companies on the web that sell the Sony digital cybershot camera. Also local places like Walmart, Radio Shack and Best Buy sell them.
Sony digital video camera recorders can be purchased from online retailers like Best Buy, Wal-Mart, Target, and plenty of others. Any electronics based sites will sell them too.
Sony makes four models of Sony Digital Video Camera Recorders. They are the standard, the HD, the 3D HD, and the projector. These video cameras come in a variety of colors. The Sony Digital Video Camera Recorder is a great item to have to keep all your memories stored.
You can purchase a sony digital video camera recorder at many locations. Your best options are amazon and eBay as they offer the best discounts and prices.
The Cyber-shot digital camera is a Sony product. These cameras are valued for being pocket-sized and also for their point and shoot capability. Cameras are available in a variety of colors and many feature touch screens.
What is the best camera to use for taking pictures of birds and other animals from far away what's the best camera
Many different types of cameras are equivalent to the Sony digital camera but it's really a matter of personal opinion and judgement. One person can have different photographic needs and standards which will sway their judgement to the camera that best supports their need, which will in turn curve t…heir opinion of which camera or cameras meet equivalence standards. ( Full Answer )
For point and shoot cameras, the Sony DSCS75 Cyber-shot gets the best reviews. The DSCP8 Cyber-shot and DSCP2 Cyber-shot also get good scores from users.
A Sony digital camera can hold a variety of images. Most cameras can only hold a handful of cameras without inserting a memory stick. The number of pictures it can hold depends on the resolutions of the picture.
The answer to this question would be dependent on the type/model of Sony camera which the customer is looking to be purchased. Certain models, in having a greater amount of capabilities, will be priced higher than more basic models. On average cameras will run between $200-$600 though.
The Sony Cybershot camera varies in its pixels. Sony Cybershots are available in many different pixel sizes as well as different model numbers. The most common pixels available in these cameras purchased are 12mp, 14.1mp, 16mp, and 18mp.
The Sony Cybershot DSC W100 digital camera can be purchased online from websites like Amazon, Sony, eBay and Get Cheap Camera shop online. This camera makes a great gift for avid photographers.
The first Sony digital camera was released in 1996 by Sony Worldwide Ltd. The digital camera was a forerunner to today's modern array of digital cameras and SLR cameras. The 1996 model had a digital viewfinder and was derived from a camera made by Kodak and other competitors.
There are many different models of Sony digital video cameras available with many different levels of performance, features and price ranges. One of the most highly rated for those on a budget is the Sony Handycam HDR-CX130, while if price is no object one may wish to check out the Sony HD HVR-Z5U.
Sony has four main types of digital cameras that it creates. These four categories of digital cameras are the Sony Cyber-shot series (point and click), Alpha NEX cameras, Alpha DSLR cameras, and video cameras and camcorders.
The model you are after is the DSG-W610G. Unfortunately, the DSG-W610/G is no longer available on the Sony official web page. One would have to try out eBay or Amazon, perhaps Argos to purchase this digitial camera.
One can purchase a Sony DSC digital camera at an online reseller such as "Amazon" or"BHPhotoVideo". One can also purchase these cameras from a retail store or directly through Sony's website.
The Sony Cybershot is a popular brand and model of digital camera. Camera cases for this camera can be found at most retailers that sell digital cameras such as Best Buy, WalMart, Target, Amazon and many others. Camera cases to fit the Sony Cybershot can also be purchased on eBay for low prices.
Sony is the electronics company who manufactures Cybershot digital cameras. Sony also manufactures stereo systems, televisions, DVD players, as well as other electronic devices.
To find user reviews for the Sony CyberShot digital camera, one can check out the Sony website. Another good option would be to check out different online retailers, which often have user ratings and reviews. One could also look at tech websites that have professional reviews.
The Sony Digital Cameras with the best reviews include the Sony CyberShot RX100, the Sony Alpha A77 and the Sony Nex-5n. More reviews for Sony Digital Cameras can be found on the Trusted Reviews Website.
One can purchase a Sony CyberShot camera from a number of places. One could look for this camera at specialty photograph stores or on websites such as Amazon or eBay.
The first Sony Digital SLR camera was made with the new X+30 series. This camera integrated new technology that allowed for quick photography like never before.
One can buy a Sony digital camera from: Sony, Amazon, eBay, Jessops, Pixmania, Target, Walmart, Best Buy, Sears, Argos, Very, Snap Deal, to name a few. Prices start from ÃÂ£255.
Sony digital cameras are available at most major department stores such as Target, Walmart and Sears. Some large malls will have The Sony Store. It carries a large selection of Sony cameras.
A Sony Digital SLR camera can be purchased at electronics stores such as Best Buy or Future Shop. Both have stores online. Or, one can search on Amazon or eBay.
The least expensive touch screen camera that Sony manufactures is the Sony Cyber Shot. The cameras range in price from just over a hundred dollars to just over four hundred dollars. The cameras have a range of other fine features along with being a touch screen digital camera.
There are a lot of places in order for one to purchase a Sony Cybershot camera. However, it is strongly suggested that one should check out from the website Amazon.
You can purchase a pink Sony digital camera from technology or office supplies stores like Best Buy or Staples. If you don't have a store like this near you, don't forget to check the store's online website. Usually, you can find more options when searching for a camera online than you can in the …store. ( Full Answer )
A Sony digital camera can be purchased from most good electronics retailers in the United Kingdom, such as Currys and Argos, or even Sony's own store.


text:
The Birth of the Modern : World Society 1815-1830
A chronicle of the "Age of Reaction," the fifteen-year period from 1815 to 1830, describes how this period was actually one marked by new ideas, inventions, and technological advances and laid the foundations for the modern world. Reprint.
- Paperback | 1095 pages
- 134.62 x 200.66 x 45.72mm | 952.54g
- 30 Jun 1992
- HarperCollins Publishers Inc
- New York, NY, United States

domain: history


text:
Cell-free fetal DNA (cffDNA) is released into the maternal circulation from trophoblastic cells during pregnancy, is detectable from 4 weeks and is representative of the entire fetal genome. The presence of this cffDNA in the maternal bloodstream has enabled clinical implementation of non-invasive prenatal diagnosis (NIPD) for monogenic disorders. Detection of paternally inherited and de novo mutations is relatively straightforward, and several methods have been developed for clinical use, including quantitative polymerase chain reaction (qPCR), and PCR followed by restriction enzyme digest (PCR-RED) or next-generation sequencing (NGS). A greater challenge has been in the detection of maternally inherited variants owing to the high background of maternal cell-free DNA (cfDNA). Molecular counting techniques have been developed to measure subtle changes in allele frequency. For instance, relative haplotype dosage analysis (RHDO), which uses single nucleotide polymorphisms (SNPs) for phasing of high- and low-risk alleles, is clinically available for several monogenic disorders. A major drawback is that RHDO requires samples from both parents and an affected or unaffected proband, therefore alternative methods, such as proband-free RHDO and relative mutation dosage (RMD), are being investigated. cffDNA was thought to exist only as short fragments (<500 bp); however, long-read sequencing technologies have recently revealed a range of sizes up to ∼23 kb. cffDNA also carries a specific placental epigenetic mark, and so fragmentomics and epigenetics are of interest for targeted enrichment of cffDNA. Cell-based NIPD approaches are also currently under investigation as a means to obtain a pure source of intact fetal genomic DNA.
Rare diseases are a heterogenous group of disorders each typically affecting less than one in 2000 people within the general population . More than 6000 unique rare diseases have been entered in the Orphanet database to date, the majority of which arise from inherited or de novo single-gene anomalies that result in chronic and sometimes life-threatening implications for patients . The three main classes of rare monogenic disorders are those which have autosomal recessive (AR), autosomal dominant (AD), and X-linked modes of inheritance, with an estimated prevalence of 35.02%, 23.78% and 5.63%, respectively, and thus accounting for more than 60% of all rare genetic diseases . While many of these disorders are not currently curable or preventable, several therapies and interventions have been developed which, if implemented in utero or at an early postnatal timepoint, could improve the quality of life of affected individuals. As such, prenatal testing has played a pivotal role in shaping pregnancy management as well as the clinical outcome of patients with rare monogenic disorders, either by allowing early initiation of therapy or by allowing parents choices with regard to pregnancy management. Historically, access to the fetal genotype has relied upon invasive sampling methods (i.e. amniocentesis and chorionic villus sampling [CVS]) which have been thought to carry a small but significant risk of miscarriage (∼0.1–0.3%) . Results from a recent meta-analysis, however, suggest that there is no increased risk associated with amniocentesis or CVS , but outcomes depend on the skill of the clinician offering testing and this can be variable. Even so, findings from extensive patient surveys suggest that less invasive procedures are preferred where available [4–6], necessitating continued focus towards development of methods that enable non-invasive prenatal diagnosis (NIPD) of single-gene disorders.
In 1997, analysis of cell free DNA (cfDNA) identified Y-chromosome genomic material circulating in the blood of pregnant women carrying male fetuses  (Figure 1). We now know that cell-free fetal DNA (cffDNA) is representative of the entire fetal genome  and, as such, has provided unprecedented access to the fetal genome through non-invasive sampling (i.e. venous blood draw). cffDNA originates from placental trophoblastic cells , is shed into the maternal bloodstream in a highly fragmented form and is detectable from as early as 4 weeks of gestation [10,11]. The average length of cffDNA fragments has been reported to be ∼143 bp, and maternal cfDNA ∼166 bp, as a result of fragmentation within the linker regions flanking nucleosomes, or at the nucleosome binding sites, respectively [8,12]. Crucially, this value has recently been suggested to be biased by the use of short-read sequencing technologies, and longer cfDNA fragments (ranging from 500 bp to ∼23 kb) have since also been detected in maternal circulation as a result of developments in long-read sequencing technologies  (Figure 1). Yu and colleagues reported that the proportion of fragments over 500 bp were approximately 15%, 20% and 32% across the three trimesters of pregnancy, respectively .
Timeline of NIPD milestones
In addition to the non-invasive aspect of cffDNA acquisition for prenatal diagnosis and screening, a further advantage of this method is the stage of pregnancy at which samples can be obtained. Invasive methods are typically carried out from 11 weeks of gestation onwards , whereas reliable levels of cffDNA for non-invasive clinical testing can theoretically be obtained from ∼7 weeks, as is the case for fetal sexing , providing additional valuable time for diagnosis and informing choices for pregnancy management [16,17]. The quantity of cffDNA in circulation is otherwise referred to as the fetal fraction (FF), and the fetal DNA is cleared from maternal circulation shortly after birth making it specific to ongoing pregnancy . In a study measuring cfDNA obtained from 1949 high- and low-risk singleton pregnancies, the average FF at 11–13 weeks of gestation was reported to be ∼10%, increasing by 2.6% per week from 8 to 10 weeks, 0.2% per week between 10 and 20 weeks, and 0.7% per week thereafter . The authors reported that FF was positively correlated with gestational age and negatively correlated with maternal weight , although there is still limited consensus on the precise aetiology of FF variability across individual pregnancies . In addition to gestational age, maternal weight/body mass index (BMI)  and natural biological variation , several other contributing factors have been suggested, including fetal aneuploidy (thought largely to be related to placental size), and pregnancy complications (and related pathology).
A decade following the discovery of cffDNA, Down syndrome was detected by analysis of cfDNA in the maternal circulation in a pregnancy where the fetus had Trisomy 21 (T21) . Since then, non-invasive prenatal testing (NIPT) via cfDNA has been implemented clinically in more than 60 countries worldwide , specifically to screen for the common aneuploidies (i.e. T13, T18 and T21) . NIPT for aneuploidy requires confirmation of a positive result by invasive testing because of the risk of discordant results which may be caused by confined placental mosaicism (CPM), the existence of maternal chromosomal rearrangements, maternal neoplasia-derived cfDNA, and cffDNA released from a vanishing twin [25,26]. Conversely, NIPD for single gene diseases in families at known increased risk does not require follow-up testing as maternal genomic DNA is accounted for during the analysis, and CPM is extremely rare in monogenic disorders .
The first research papers describing NIPD for monogenic disorders, namely achondroplasia  and myotonic dystrophy , were published in 2000 (Figure 1). Over the years, a number of authors have published reports of cfDNA analysis for a variety of monogenic disorders, but use in clinical service has largely been confined to fetal sex determination [30,31] and rhesus D blood group (RHD) status [32,33] in RHD negative women (Figure 1). Since, the repertoire of monogenic disorders that can be tested for using NIPD has increased to include FGFR2- and FGFR3-related syndromes [34–37], cystic fibrosis (CF) [38,39], spinal muscular atrophy (SMA), Duchenne and Becker muscular dystrophies (DMD, BMD) [40–42], as well as bespoke testing for families with rare mutations  (Figures 1 and 2). Although the aggregated incidence of monogenic disorders is relatively high, individually cases are rare, and this has hindered the widespread clinical implementation of bespoke testing. Additionally, the high background of maternal cfDNA is a significant challenge with regards to working with cffDNA, particularly for the detection of maternally inherited variants.
Non-invasive prenatal tests available and in development for diagnosis of monogenic disease
Expanded NIPD for monogenic disorders is not only important for informing the reproductive choices of prospective parents but also for health service planning and provisioning. This review will cover the tests that are currently in clinical service for NIPD of monogenic disorders in high-risk pregnancies, as well as the strategies that are being developed towards future clinical implementation, and includes a brief overview of the tests which are commercially available for NIPT in low-risk pregnancies.
Paternally inherited and de novo variants
qPCR and PCR-RED
A relatively straightforward approach to NIPD is for the detection of paternally inherited or de novo variants which are, by definition, not present in the maternal fraction of cfDNA . Several PCR-based methods have been used, including real-time quantitative PCR (RT-qPCR) for fetal sex determination. Digital PCR (dPCR) has also recently been implemented clinically for the purpose of identifying male fetuses in families at risk for X-linked disorders where conventional qPCR approaches are not applicable , and for paternal mutation exclusion testing whereby the absence of the paternal variant indicates that the fetus is not affected  (Figure 1). Determination of fetal sex using non-invasive methods reduces unnecessary further testing or treatment, such as in the instance of a female pregnancy in families at risk of X-linked disorders (e.g. BMD/DMD ) (Figure 2), and in cases of congenital adrenal hyperplasia (CAH) where treatment with dexamethasone can be restricted to female fetuses [46,47]. Some of the first tests for NIPD of monogenic disease to be delivered clinically were based on PCR followed by restriction enzyme digestion (PCR-RED), specifically for the diagnosis of two FGFR3 disorders (achondroplasia and thanatophoric dysplasia) [34,35]. There are several limitations to the PCR-RED approach, however, including that it is gene- and variant-specific, requires gel-based analysis which can be subjective, is not applicable to all mutations or for cases where the causative gene is unknown, and it has an inconclusive rate of 8% .
PCR and NGS
Targeted sequencing of specific genomic loci through PCR followed by next-generation sequencing (PCR-NGS) has emerged as a more sensitive and accurate NIPD approach to conventional PCR-based methods, with a broader mutation detection range for single gene disorders (Figures 1 and 2). This approach can be used to screen for all variants within a gene, for example, autosomal dominant FGFR2- and FGFR3-related conditions . Recently, PCR-NGS has been used for the prediction of fetal ABO blood group . For autosomal recessive disorders, such as CF  and β-thalassaemia , PCR-NGS is employed for paternal mutation exclusion (Figures 1 and 2) whereafter detection of the paternal allele requires invasive follow-up testing to determine inheritance of the maternal variant. Additionally, accredited clinical services using PCR-NGS are available for bespoke testing of paternally inherited mutations in families with a known risk for a particular monogenic disease, or where a de novo mutation has been detected in a previous pregnancy [27,37,38] (Figures 1 and 2). This approach, however, has not yet been widely clinically implemented owing to its costly and labour-intensive nature.
Autosomal recessive and inherited X-linked disorders
While detection of de novo or paternally inherited variants in cfDNA is relatively straightforward, accurately assigning maternally inherited variants poses a significant challenge owing to the high background of maternal plasma DNA. PCR-NGS is not fully quantitative owing to relatively low read depths, and thus is unable to assign maternally-inherited variants to the FF. This instead requires the use of highly sensitive techniques that can accurately detect small imbalances between wild-type (WT) and pathogenic variants, such as relative haplotype dosage analysis (RHDO) and relative mutation dosage (RMD) (Figures 1 and 2). Newer molecular counting techniques are also being developed to facilitate NGS-based maternal variant detection in cfDNA, discussed in more detail below.
RHDO involves linkage-based methods for variant calling whereby combined counts from thousands of heterozygous SNPs (otherwise referred to as informative SNPs) within the same haplotype surrounding the variant-of-interest are taken into consideration  (Figure 3). For autosomal recessive conditions, haplotype phasing of the risk-associated and WT alleles is carried out using NGS on genomic DNA obtained from the mother, father, and an affected or unaffected sibling (i.e. the proband) (Figure 3A,B). For X-linked conditions, the paternal sample is not required for phasing of the high- and low-risk alleles (Figure 3A,B). Sequencing analysis of the maternal plasma DNA is then performed, and SNPs are computationally assigned to a particular type according to their identity relative to the parental genotypes  (Figure 3C). Bayesian statistical modelling, using tests such as the sequential probability ratio test (SPRT), determines the relative increase or decrease in informative SNPs across the target haplotype, and thereby predicts fetal inheritance of the disease-associated, or WT, alleles  (Figure 3C). RHDO is currently clinically available for NIPD of the autosomal recessive disorders CF , SMA , and CAH , as well as X-linked DMD-related muscular dystrophies  (Figures 1 and 2). RHDO is still in the developmental setting for α- and β-thalassaemia (HBA and HBB) , retinoblastoma (RB1) , Ellis-van Creveld syndrome (EVC), factor 8 (F8) disorder/haemophilia A, and mucopolysaccharidosis type II (MPS II)/Hunter syndrome  (Figure 2).
Schematic overview of RHDO and RMD for NIPD of AR and inherited X-linked conditions
A major advantage of RHDO is that it is not limited by the variant type. However, several challenges exist that have limited widespread implementation of this technology into the clinic. These include difficulties performing RHDO on consanguineous couples owing to the shared haplotype, and the requirement for a sample from both parents as well as an affected or unaffected proband or family member in order to perform the phasing analysis. Improvements to this approach are under investigation, including proband-free RHDO using long-read sequencing (Figure 1). Alternatively, RMD is a method which is highly sensitive and theoretically capable of diagnosing autosomal recessive and X-linked disorders requiring only a maternal blood sample  (Figures 1 and 2). Proband-free RHDO and RMD are discussed in more detail below.
In the developmental pipeline
Conventional RHDO relies on inferring the high-risk haplotype based on the SNP profile of an affected or unaffected proband; however, several direct haplotyping methods have recently been developed to facilitate parental haplotype phasing in circumstances where access to additional samples is unavailable. Two main approaches have been investigated for proband-free RHDO, including targeted locus amplification (TLA) [55,56] and microfluidics based linked-read sequencing (although the associated 10X Genomics technology is no longer available) [53,57–59]. As recommended by the American College of Obstetricians and Gynecologists (ACOG) , pre-pregnancy or prenatal carrier screening should be undertaken at a global population level for relatively common autosomal recessive disorders, such as SMA, CF and haemoglobinopathies. For these conditions, it is likely therefore that high-risk pregnancies will be identified in couples with no previous children, and therefore the development of universal direct-haplotyping tests could open up the possibility of RHDO for these first-time parents.
Recent advances in single molecule long-read sequencing platforms, such as those developed by Oxford Nanopore Technologies (ONT, Oxford, U.K.)  and Pacific Biosciences (PacBio, Menlo Park, CA, U.S.A.) , also have the potential to enable proband-free RHDO, as demonstrated in a recent study with relevance to β-thalassaemia, whereby ONT long-read sequencing was used to increase the length of individual haplotype blocks used for phasing analysis, and consequently improve statistical robustness . In this study, Jiang and colleagues reported a failure to determine the maternal haplotype in one family as the closest heterozygous SNP was located outside of the PCR fragment boundary and thus not linkable to the variant-of-interest . Further investigation is required to determine how common such local regions of homozygosity may be, and how this could negatively impact the utility of maternal haplotype phasing by long-read sequencing. PCR-related errors, including template-switching, should also be carefully considered with this approach.
cffDNA long-read sequencing has the potential to further increase the resolution and accuracy of fetal genotype classification as recombination events near the mutation site are more likely to be identified. Furthermore, the newly developed ONT readfish toolkit allows selective enrichment of reads-of-interest in real-time, which could assist with increasing sequencing depth specifically within the desired target regions . Unfortunately, the error-rate of ONT is currently relatively high (∼5%) , although newer base calling models and chemistries are constantly being developed to improve accuracy towards levels that may be acceptable for clinical implementation. At present, PacBio sequencing offers greater accuracy, but the overall cost of this technology is higher than that of ONT which may preclude its use in publicly funded settings.
RMD is an alternative method to RHDO, which has been investigated for the detection of maternally inherited variants in cfDNA. RMD is designed to directly detect single mutations, and operates under the assumption that there is a 50:50 ratio of the WT to pathogenic alleles in non-pregnant carriers  (Figure 3D). Similarly, if the mother and fetus share the same genotype, allelic balance is expected (Figure 3D). If the fetus is homozygous for the maternal pathogenic variant, however, a slight increase in the risk-associated allele relative to the FF will result, with the converse being true for a homozygous WT fetus (Figure 3D). For RMD to reliably replace invasive testing, the chosen method should be accurate at similar timepoints despite the low abundance of cffDNA in maternal circulation (i.e. at ∼11 weeks of gestation).
dPCR is the leading technology that has been applied to molecular counting [66–68], and its application in NIPT and NIPD research and development has been reviewed comprehensively elsewhere [69,70]. dPCR involves sample partitioning and target amplification within discrete reaction units thereby improving detection of rare variants within a high background of maternal plasma DNA, relative to conventional PCR-based methods, without the need for a standard curve [68,71,72]. To date, dPCR-based RMD for NIPD has not reached the clinic. However, this approach has shown clinical promise in several proof-of-concept studies for the detection of both paternally and maternally inherited variants, including for haemophilia [73,74], sickle cell disease [54,75], monogenic diabetes , β-thalassaemia [77–79], CF [80,81], inherited deafness , achondroplasia , and others [84,85] (Figure 2). The utility of haplotype-free RMD using dPCR is being considered for copy number variation (CNV) detection in autosomal recessive diseases, such as SMA, where gene copy number is negatively correlated with disease severity .
Previous generations of dPCR technologies were based on microfluidic devices with limited numbers of sample partitions [66,67]; however, several improvements have since resulted in the emergence of droplet dPCR (ddPCR)  (Figure 1). ddPCR is a highly sensitive, quantitative and high-throughput approach that involves separation of individual genomic targets into thousands (>10,000) of nanolitre-sized droplets using water–oil emulsion technology. The presence or absence of a variant-of-interest (i.e. WT vs pathogenic or maternal vs paternal) is ascertained on a droplet-by-droplet basis using fluorescence indicators.
RMD is clinically useful for detecting common pathogenic SNPs in the population using predesigned assays rapidly and at a low cost. A minimal FF threshold of >4% has typically been applied in the research setting using different methodologies for RMD-based testing for SNPs [74,86]. A major drawback of this approach that has delayed clinical implementation to date has been several reports of small numbers of incorrect and/or inconclusive results when using this technique [75–79,85]. For instance, Barrett and colleagues reported 5 misclassified (i.e. 1 false-positive and 4 false-negative) and 2 inconclusive results from a large cohort study of 59 individuals using ddPCR-based RMD for NIPD of sickle cell disease . Sawakwongpra and colleagues similarly reported a misclassification rate of ∼20% (i.e. 5/24 cases) using this approach . D’Aversa and colleagues reported 1 misclassified result out of 52 samples using ddPCR in the context of β-thalassaemia . Perlado and colleagues also reported 1 false-positive and 5 inconclusive results . Efforts to optimise the ddPCR methodology have been made by Constantinou and colleagues in their recent study which focused on RMD for β-thalassaemia; however, 1 misclassified and 6 inconclusive results out of 40 cases were still observed . Insufficient FF (<4%) is believed to be a major contributor towards such discrepancies, although this cannot fully explain the results which have been described . The minimal FF requirement for RMD using ddPCR is thus still somewhat uncertain. In addition to the FF, the total starting number of DNA molecules as well as the depth of the assay are also important contributors towards accurate genotype prediction using RMD. Purely setting a FF threshold is not necessarily a solution towards preventing incorrect and/or inconclusive calls. Such incorrect and inconclusive predictions, with as-of-yet inexplicable causes highlight the need for caution and further optimisation of the technology before NIPD using ddPCR-based RMD can be clinically implemented. Large-scale studies and machine learning approaches could improve the predictive value of RMD using dPCR in the future.
RMD has several advantages over RHDO, including that there is no requirement for paternal or proband samples, and that it is possible to detect de novo mutations provided the variant is suspected. Equally, however, RMD using dPCR has a number of disadvantages compared to RHDO. For instance, as RMD is focused only on a single mutation site while RHDO is haplotype-specific and covers lengthy genomic regions containing multiple SNPs, the possibility for multiplexing in a single assay is limited, and statistical robustness reduced. Furthermore, RMD is not applicable to large structural variants and mutations within highly repetitive regions or loci with similar sequence context elsewhere in the genome. As such, more sensitive approaches to RMD that are still achievable using only a maternal plasma sample are being investigated. These include circulating single-molecule amplification and resequencing technology (cSMART), which involves the introduction of UMI tags, circularization of tagged genomic DNA, inverse PCR, and sequencing. cSMART was developed as a proof-of-concept study for Wilson disease (ATP7B) using Sanger sequencing  and, more recently, has employed NGS technologies, showing clinical utility for autosomal recessive non-syndromic hearing loss (GJB2 and SLC26A4) [89,90], β-thalassaemia (HBB) [91,92], methylmalonic acidaemia cblC type (MMACHC) , and phenylketonuria (PAH) . Other studies have also described the use of barcode-enabled NGS to facilitate molecular counting with single base pair resolution [95–97], nested PCR and NGS , as well as size-based enrichment of cffDNA prior to diagnostic analysis [54,97].
Fragmentomics and epigenetics
The term ‘fragmentomics’ has been adopted to describe the fragmentation properties of cfDNA, including the size distribution and biochemical nature of the free ends . These assets can be leveraged to facilitate targeted analysis as well as enrichment of cffDNA. Additionally, the presence of longer cfDNA fragments provides a means to obtaining haplotype information from single cfDNA fragments using long-read sequencing technologies (PacBio and ONT) . Long-read sequencing of cffDNA could therefore improve visualization of larger genomic aberrations, such as insertions, deletions and other sub-chromosomal structural rearrangements, and some triplet repeat expansions, which are difficult to detect by short-read sequencing. In addition, these longer fragments have enabled genetic-epigenetic tissue mapping on a single molecule level [9,13]. The abundance of CpG sites on the long cfDNA molecules means that single-molecule methylation analysis can be used to deduce the tissue of origin of individual plasma molecules. By first identifying cfDNA fragments containing the maternal-specific allele followed by methylation analysis to ascertain whether or not this allele is present on placenta-derived cfDNA molecules, the maternal inheritance of the fetus can be determined without the need for the sensitive molecular counting and dosage-based techniques previously described for both RHDO and RMD. The proof-of-principle study demonstrating this technique has been carried out using SMRT sequencing , which currently carries a high cost. However, as sequencing costs continue to decline and with the improving accuracy of ONT sequencing this approach will no doubt become viable for clinical practice in the future.
Fetal DNA in maternal circulation does not only exist in the cell-free, fragmented form, as fetal and placental cells are trafficked into the maternal bloodstream from as early as 4–6 weeks of pregnancy and have been successfully isolated during these early timepoints [100,101]. An advantage of a cell-based source of fetal DNA is that the genomic material remains intact, thereby circumventing some of the challenges experienced with short-read cfDNA such as the limited size of variants that can be detected and difficulties with haplotype phasing  (Figure 1). Four major populations of fetal cells that are trafficked through the placenta into the bloodstream have been detected. Trophoblasts and nucleated red blood cells (early erythrocytes) (reviewed in ) exist transiently in circulation, are thus specific to the ongoing pregnancy, and provide a pure population of fetal or placental cells (fetal cells holding an advantage since they are not subject to confined placental mosaicism). The two other major classes of circulating cells are fetal lymphocytes and stem/progenitor cells, however these were found to persist for several years following birth and so have garnered less attention for cell-based NIPD .
One of the major limitations of a cell-based approach that has hindered its clinical implementation to date is rooted in the relatively low abundance of circulating fetal cells within the high background of nucleated maternal haematopoietic cells [102,105]. For instance, a recent study reported isolation of, on average, 2.5 cells per mL of blood across 8 cases . Unlike the FF of cfDNA which increases with pregnancy progression, the optimal window for collection of fetal cells from the maternal bloodstream is believed to be ∼10–14 weeks, during which time there is a high level of placental vascularisation . Techniques are therefore required for the enrichment of fetal/trophoblastic cells, which can also be done alongside depletion of maternal cells. After enrichment, isolation of fetal cells then requires high-throughput processing for the detection of multiple fetal cell markers. Recently, a combined effort between medical genetics and materials science has enabled innovative advancements towards improving detection, enrichment, isolation and characterization of cell-based fetal DNA .
Another limitation of these cell-based approaches is that whole genome amplification is required prior to single cell sequencing, and this makes this technique susceptible to significant allele dropout and amplification errors . It is feasible that optimization of isolation methods may overcome the challenge of low yields and a relatively narrow sampling window; however, the techniques are both time-intensive and costly for clinical implementation, and currently none of the many published methods of cell selection and identification have been validated for clinical use . Trophoblast retrieval and isolation from the cervix (TRIC) is an alternative, semi-invasive method to obtain fetal cells which has been proposed to improve yields without a known associated risk of miscarriage [109,110]. Extraction of mononuclear extravillous trophoblasts (EVTs) by TRIC was reported to provide ∼500–1500 cells per sample, far greater than from maternal peripheral blood samples. A possible limitation towards the clinical implementation of TRIC is that trained personnel are required for cell collection from the cervix, although this is not too dissimilar to commonly performed cervical cancer screening methods.
While cell-based NIPD has great promise in clinical practice to be a useful alternative to CVS and amniocentesis, much work is still required to improve the methods for high-throughput isolation of pure fetal cell populations and to ensure consistent test performance at low cost.
Commercial screening for low-risk pregnancies
NIPD is currently commercially available for low-risk pregnancies (Figures 1 and 2). One such screening test, marketed under the brand name Vistara (Natera, Inc., San Carlos, CA, U.S.A.), screens for 25 autosomal dominant and X-linked conditions across 30 genes using a unique molecular indexing (UMI) technique for the NGS analysis  (Figure 2). This test requires genomic DNA from both parents to be tested alongside the cfDNA in order to assist with the interpretation, and it cannot detect variants which are maternally inherited (including those which are also X-linked). A recent review of this service looked at the results for 2208 women, of which 125 (5.7%) were positive . The authors report no false-positive or -negative results, with a follow-up rate of 53.6%. It is important to take note of this low rate of follow-up in this study, reflected in a statement made by ACOG regarding single gene cfDNA screening, which states that there is insufficient data to provide information regarding the positive and negative predictive value in the general population, and therefore it does not currently recommend this screening in pregnancy . In addition to the lack of long-term follow-up, it should also be noted that the minimum NGS coverage requirements for the target regions is ≥97% [111,112]. Although this information is provided in the literature, the majority of patients will likely be unaware that coverage of certain genes may not be 100%, and the impact that this could have on the interpretation of their result. Of note, the minimal FF requirement for this test is 4.5% .
Another commercially available screening test is the UNITY Screen™ (BillionToOne Inc., Menlo Park, CA, U.S.A.) (Figure 2). This test offers a maternal carrier screen for four recessive conditions, including CF, SMA, and haemoglobinopathies, as recommended by ACOG , with reflex cfDNA testing for all those identified as carriers . This RMD-based screening test, which uses a Quantitative Counting Template (QCT) molecular counting approach rather than UMIs, can therefore provide a personalised fetal risk assessment without the need for a paternal sample. While the minimum FF required for the UNITY Screen™ is not explicitly stated on the company website, reliable results were reported to be obtained at a FF ≥ 5%, according to their recent publication . With respect to CF and the group of inherited haemoglobinopathies, the UNITY Screen™ is not fully exhaustive for all disease-causing recessive variants within the CFTR and HBA/HBB genes, respectively (Figure 2). Even so, a recent review of this carrier screen with reflex single gene NIPT identified that, as first-line screening, it could offer significant cost savings for the healthcare system when compared to traditional carrier screening, and also a 2.4-fold improvement in the detection of affected fetuses . The authors go on to state, however, that additional studies will be required to further assess the clinical utility, and there is as yet no support from national bodies for such screening based on analysis of cfDNA to be implemented.
Commercial availability of NIPD tests offers expansion of the service to include low-risk pregnancies; however, a growing concern in the health-care community is that expert pre- and post-test counselling may not be available to patients. Interpretation of results is essential to take into consideration the possibility of factors such as variable disease expressivity, incomplete penetrance, incomplete gene coverage, and risks of false-negative or false-positive results. Furthermore, this should be clearly distinguished from NIPD offered in pregnancies at known increased risk because of a family history or ultrasound findings. In the latter situation, cfDNA testing is diagnostic and does not require confirmation of positive findings by analysis of a fetal sample obtained by invasive testing. If the commercial test is offered in low-risk pregnancies, invasive testing will be required to confirm high-risk results, at least until sufficient data are available to demonstrate the sensitivity, specificity and positive predictive value of these tests.
The ability to examine the fetal genotype at single nucleotide resolution from within maternal plasma DNA has revolutionised prenatal care. A plethora of approaches have been developed for low-level variant detection for paternally inherited and de novo variants, and dosage-based and molecular counting techniques for the detection of maternal variants. Proof-of-concept studies indicate that several additional methods for NIPD of monogenic disease have clinical utility, notably the discovery of long cfDNA fragments, and the next phase will be critical for bridging the gap between the research and clinical settings. While no single strategy will cover all possible rare diseases, keeping apace with technological advancements, streamlining workflows and reducing the overall cost of testing will be essential for the expansion of NIPD for monogenic disease in the clinic, but this can be challenging given the rarity of many conditions. Importantly, the minimal FF, starting genomic material, and depth of assay required across the various NIPD methodologies in order to obtain consistently accurate fetal genotype predictions across all modes of inheritance require deeper investigation.
Even if the possibility exists to carry out NIPD earlier in pregnancy than for invasive testing, there needs to be confidence that consistently high levels of sensitivity and specificity will be obtained. This could vary depending on the suspected diagnosis, and the chosen method for carrying out NIPD. There is an ongoing debate as to who should have access to testing, and the burden of information on patients as well as clinical researchers must be carefully considered prior to the implementation of new tests into the clinic. In addition, even with clear selection guidelines, disparities with regards to access and availability of resources must be taken into account so as to reduce inequalities. Conversations across multidisciplinary teams is essential for relevant case selection and to balance clinical resources with diagnostic yield. With the rapid strides being made in gene therapy for rare monogenic disorders, the panel of genes and diseases we are able to include is ever-growing, if we are to work towards accurate diagnosis and treatment of affected children from the earliest timepoint.
There is no data available for sharing relating to this manuscript.
The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
This work was supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital, London, U.K. (to B.H. and E.S.; to L.S.C. (in part)).
Open access for this article was enabled by the participation of University College London in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with JISC.
CRediT Author Contribution
Britt Hanson: Writing—original draft. Elizabeth Scotchman: Writing—original draft. Lyn Chitty: Conceptualization, Supervision, Funding acquisition, Writing—review & editing. Natalie Chandler: Writing—review & editing.
American College of Obstetricians and Gynecologists
Becker muscular dystrophy
congenital adrenal hyperplasia
cell-free fetal DNA
copy number variation
confined placental mosaicism
circulating single-molecule amplification and resequencing technology
chorionic villus sampling
Duchenne muscular dystrophy
digital polymerase chain reaction
next generation sequencing
non-invasive prenatal diagnosis
non-invasive prenatal testing
Oxford Nanopore Technologies
PCR-restriction enzyme digestion
quantitative polymerase chain reaction
relative mutation dosage
rhesus D blood group
relative haplotype dosage analysis
spinal muscular atrophy
single nucleotide polymorphism
sequential probability ratio test
targeted locus amplification
trophoblast retrieval and isolation from the cervix

domain: medical


text:
Today I’m not feeling too well which I guess explains why I’m on tumblr.
I started posting on here quite often when I was with Joe. But now Joe isn’t in my life anymore.
And you might be feeling sorry for me right now but don’t be. Joe and I were really never meant to be. I kept telling myself that something would happen between us but in actuality I knew the relationship was doomed.
By the way, when the first thing all your friends and family members say when they meet your partner is: “is he gay?” END THINGS RIGHT AWAY
Anyways, I’m pretty sure I only stayed with Joe because I was bored and we had great sex because after I started college, I ended things immediately with him.
Wanna know something funny?
I made Joe cry.
I think it’s funny because months earlier I had told him that I was developing feelings for him and he shut me down telling me we were never going to be anything.
Well, Joe ended up crying because I told him I was moving on and didn’t want to date him.
It’s funny the way things work.
College is great by the way.
But I’ll save that for another day when I’m in a good mood.
On August 30th, 2013, my nephew, Zack Thien Ho passed away.
For the first time in my life, I felt pain—I really felt it. And it was like no other pain that I’ve felt in all my years.
The last time I dealt with death was when my grandmother passed away. But even then I didn’t feel this pain. Probably because I knew she was going to die. I knew that she was sick and her time was limited. I was prepared for her death. And I guess that made it sort of okay…
But Zack was a month old. And no one ever prepared me for this.
No one prepared me for this pain. No one prepared me for the phone call from my mother bawling her eyes out. No one prepared me for the moment I would walk into the hospital room only to find my sister cradling her dead son.
Just like no one can give me answers to all the questions I’ve been pondering.

domain: psychology


text:
Citing concerns regarding the operations of the Long Island Power Authority, Gov. Andrew Cuomo today directed New York State Inspector General Ellen Biben to conduct a thorough audit of the organization that provides power to more than 1.1 million customers.
Cuomo cited concerns that LIPA may be raising rates in a manner “to avoid triggering a required review by the Public Service Commission” as well as overbilling customers.
Cuomo noted that annual delivery charge increases of less than 2.5 percent are not subject to scrutiny by the PSC, while the last two increases of 2.1 percent and 1.9 percent fell just short of that. Cuomo in a release issued by his office said that raises the possibility that LIPA is “increasing its rates just below the threshold to avoid a PSC review.”
Cuomo then directed the Inspector General to focus the audit on LIPA’s billing and delivery charge practices “to ensure Long Island ratepayers are treated fairly and are not subjected to unnecessary and avoidable rate hikes.”
“The Inspector General’s audit of how LIPA sets its rates will make sure Long Islanders know where their money is going, especially since they pay among the highest energy rates in the nation,” Cuomo said. “We must make sure that LIPA is following the letter of the law when it comes to how much it charges ratepayers.”
Cuomo also cited concerns of Long Island elected officials including State Sen. Kenneth P. LaValle and Assemblyman Robert K. Sweeney, who greeted the decision as a welcome way of providing oversight to the embattled electric authority.
“LIPA’s promise, when formed, was to lower the rates of long-suffering Long Islanders,” LaValle said. “Over the years, through sleight of hand, this public utility has steadily boosted rates several-fold by calling the increases a ‘surcharge,’ and avoided scrutiny by the PSC.”
LIPA Chief Operating Officer Michael Hervey, meanwhile, said the authority “will cooperate fully” with the audit and that he is “confident that this audit will be a step along the path of restoring confidence in our rates and charges.”
LaValle and Sweeney earlier this year introduced legislation to require the PSC to review and approve LIPA’s rate increase requests if they collectively add up to 2.5 percent over 12 months, regardless of how they are described or divided.
“A number of unfortunate and questionable decisions have caused the authority to lose public confidence,” Sweeney said. “It is only through greater transparency and professional oversight that this trust can be restored. Long Islanders pay among the highest electric rates in the United States.”
The Public Service Commission has said it believes it lacks the resources to conduct a full audit of LIPA’s rates. It also questioned whether it would be able to do so under the proposed legislation, since it is difficult to evaluate rate hikes without a far-reaching understanding of an entity.
The PSC also has cited concerns regarding contradictory messages, including the legislation creating LIPA which exempted it from PSC oversight before additional requirements were promulgated requiring the commission to review hikes of 2.5 percent.
The Inspector General, however, said she believes she has the resources to examine LIPA’s practices regarding rate hikes.
“Our office has the tools and resources necessary to conduct a swift and thorough audit of the Long Island Power Authority’s rate tactics,” Biben said.
LIBN has run numerous articles regarding LIPA‘s previous use of surcharges, which often were higher than 2.5 percent, but which LIPA contended were not subject to PSC review, since they were not permanent hikes.
LIPA argued increases related to fuel costs were exempt from that 2.5 percent hike provision, further shielding it from oversight.
LIPA no longer describes a portion of its bill as surcharges, which it had said were designed to be temporary increases.
LIPA has argued that limits on its ability to raise rates could hurt its credit by potentially causing jitters among bond issuers and damaging its standing among credit rating agencies.

domain: news


text:
"Go with the Flow" is Marjory the Trash Heap's sung birthday wisdom to Boober in the Fraggle Rock episode "Marooned." She is accompanied by Philo and Gunge (as well as Mokey and Red) as they advise Boober to stop worrying so much and "focus on the positive."
The song is later resung in Lucky Fargy by Marjory the Trash Heap and Philo and Gunge.
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domain: entertainment


text:
United States District Court, D. South Carolina
REPORT AND RECOMMENDATION
a civil action filed by a pretrial detainee, proceeding
pro se and in forma pauperis. Pursuant to
28 U.S.C. § 636(b)(1) and District of South Carolina
Local Civil Rule 73.02(B)(2)(e), the undersigned is
authorized to review all pretrial matters in such pro
se cases and to submit findings and recommendations to
the district court. See 28 U.S.C. § 1915(e).
established local procedure in this judicial district, a
careful review has been made of the pro se complaint
filed in this case. This review has been conducted pursuant
to the procedural provisions of 28 U.S.C. §§ 1915,
1915A, and the Prison Litigation Reform Act of 1996, and in
light of the following precedents: Denton v.
Hernandez, 504 U.S. 25 (1992); Neitzke v.
Williams, 490 U.S. 319, 324-25 (1989); Haines v.
Kerner, 404 U.S. 519 (1972); Nasim v. Warden, Md.
House of Corr., 64 F.3d 951 (4th Cir.1995) (en banc);
Todd v. Baskerville, 712 F.2d 70 (4th Cir.1983).
Complaint has been filed pursuant to 28 U.S.C. § 1915,
which permits an indigent litigant to commence an action in
federal court without prepaying the administrative costs of
proceeding with the lawsuit. To protect against possible
abuses of this privilege, the statute allows a district court
to dismiss the case upon a finding that the action
“fails to state a claim on which relief may be granted,
” “is frivolous or malicious, ” or
“seeks monetary relief against a defendant who is
immune from such relief.” 28 U.S.C. §
1915(e)(2)(B). A finding of frivolousness can be made where
the complaint “lacks an arguable basis either in law or
in fact.” Denton, 504 U.S. at 31. Hence, under
§ 1915(e)(2)(B), a claim based on a meritless legal
theory may be dismissed sua sponte. See
Neitzke, 490 U.S. at 327.
court is required to liberally construe pro se
complaints. Erickson v. Pardus, 551 U.S. 89, 94
(2007). Such pro se complaints are held to a less
stringent standard than those drafted by attorneys.
Id.; Gordon v. Leeke, 574 F.2d 1147, 1151
(4th Cir. 1978). Even under this less stringent standard,
however, the pro se complaint is subject to summary
dismissal. The mandated liberal construction afforded to
pro se pleadings means that if the court can
reasonably read the pleadings to state a valid claim on which
plaintiff could prevail, it should do so, but a district
court may not rewrite a complaint to include claims that were
never presented, construct the plaintiff's legal
arguments for him, or conjure up questions never squarely
presented to the court. Beaudett v. City of Hampton,
775 F.2d 1274, 1278 (4th Cir. 1985); Small v.
Endicott, 998 F.2d 411 (7th Cir. 1993); Barnett v.
Hargett, 174 F.3d 1128 (10th Cir. 1999). The requirement
of liberal construction does not mean that the Court can
ignore a clear failure in the pleading to allege facts which
set forth a claim currently cognizable in a federal district
court. Weller v. Dep't of Soc. Servs., 901 F.2d
387, 390-91 (4th Cir. 1990) (The “special judicial
solicitude” with which a [court] should view such pro
se complaints does not transform the court into an
brings this action pursuant to 42 U.S.C. § 1983.
Plaintiff alleges that on May 4, 2017, at 6:30pm, while on
suicide watch, he managed to get two small razor blades. (ECF
No. 1 at 5, 7). He sliced his right wrist. (ECF No. 1 at 7).
Defendants Sweat and “Gleason” came in, and then,
Plaintiff swallowed the blades. (ECF No. 1 at 7). Defendants
were informed that Plaintiff had swallowed the blades. (ECF
No. 1 at 7). Without attending to the wrist cut or taking
Plaintiff to another facility, the three named defendants
strapped Plaintiff in a chair and gave him laxatives. (ECF
No. 1 at 7). Blood built up in his throat, and he started
choking and passed out. (ECF No. 1 at 7). He was awakened
later when he was taken out of the chair straps for five
minutes and then strapped back in the chair. (ECF No. 1 at
7). The lights stayed on all night. (ECF No. 1 at 7).
then taken out of the chair the next morning. (ECF No. 1 at
7). He was able to use a phone to inform others what happened
and that person called the news. (ECF No. 1 at 7). Around 9am
the next day, he was taken to a hospital and admitted. (ECF
No. 1 at 7). He said Defendant Abraham was very angry. (ECF
No. 1 at 7). The two blades were in his intestines per the
x-ray. (ECF No. 1 at 8). A doctor stated that he was to
remain at the hospital until a bed came open at Bryan's
Mental Health. (ECF No. 1 at 8). He passed the blades. A few
days later was told the ER needed his room and a doctor told
him he would have to wait at the detention center. (ECF No. 1
at 8). Later, he found out the detention center removed his
name from the list for placement at the mental health
facility. (ECF No. 1 at 8).
reports he has been kept in solitary confinement since June
2017 “without cause.” (ECF No. 1 at 5). He is
having problems with his medications as well. Under relief,
he states he wants to “get to mental health... and
placed in an open pod.” He requests monetary damages.
also alleges there is no law library. (ECF No. 1 at 6). He
wants access to a law library. (ECF No. 1 at 10).
1983 “ is not itself a source of substantive rights,
but merely provides a method for vindicating federal rights
elsewhere conferred.” Albright v. Oliver, 510
U.S. 266, 271 (1994) (internal quotation and citation
omitted). A legal action under § 1983 allows “a
party who has been deprived of a federal right under the
color of state law to seek relief.” City of
Monterey v. Del Monte Dunes at Monterey, Ltd.,
526 U.S. 687, 707 (1999).
§ 1983, a plaintiff must establish two essential
elements: (1) that a right secured by the Constitution or
laws of the United States was violated, and (2) that the
alleged violation “was committed by a person acting
under color of state law.” West v. Atkins, 487
U.S. 42, 48 (1988).
order to assert a plausible § 1983 claim against any
particular state actor, a “causal connection”
must exist between the conduct alleged by the plaintiff and
the particular defendant named in the suit. See Kentucky
v. Graham, 473 U.S.159, 166 (1985); Rizzo v.
Good, 423 U.S. 362, 371-72 (1976) (a § 1983
plaintiff must show that he suffered a specific injury
resulting from a specific defendant's specific conduct
and must show an affirmative link between the injury and that
conduct); Vinnedge v. Gibbs, 550 F.2d 926, 928 (4th
Cir. 1977) (for an individual to be liable under § 1983,
the Plaintiff must show that the defendant named acted
personally in the deprivation of the plaintiff's rights).
pretrial detainee's § 1983 actions are evaluated
under the Fourteenth Amendment. Bell v. Wolfish, 441
U.S. 520, 535, 537 n.16 (1979); Martin v. Gentile,
849 F.2d 863, 870 (4th Cir. 1988). Plaintiff's
rights under the Fourteenth Amendment are at least as great

domain: law


text:
An exact list of the Lords spiritual and temporal as also of the knights and commissioners of Shires, citizens and burgesses of the first Parliament of King George. Summon'd ... on the 17th day of March 1714/15, and ... continu'd, ... until the 8th day of December 1720, ...
printed for R. Gosling,
|Edition:||The eighth edition corrected.|
|Online Access:||Full text online|
No Tags, Be the first to tag this record!


text:
Monitoring Glucose Levels and HbA1c
The HbA1c is an important tool to incorporate into the inpatient evaluation. It is now accepted as a diagnostic test for diabetes, and values can supplement patient clinical history in determining the effectiveness of pre-hospitalization treatment regimens. The test can help to identify some of the 25 percent of patients with diabetes mellitus (DM) that had previously been undiagnosed and recognition of DM while inpatient may reduce their risk of readmission.1,17 Since it is relatively easy and inexpensive, it has become an “opt out” test on many order sets, is recommended in some guidelines and testing it on all patients with hyperglycemia without a value documented within the last 60 days is a required component for Joint Commission Certification in Advanced Inpatient Diabetes Care.13
Guidelines recommend that all patients have blood glucose testing upon admission and those with a BG value >140mg/dL have ongoing testing for at least 24-48 h.13 POC glucose meters are currently the method most widely used for monitoring glucose because of the rapid turnaround and need to make timely adjustments to therapy. However, there are a wide number of potential issues (shock, hypoxia, dehydration, extremes in hematocrit, elevated bilirubin and triglycerides) impacting the accuracy.18,19 Additionally, issues with some monitors and lack of Food and Drug Administration (FDA) approval for critical care or hospital use have also been raised.20,21 Outside of these analytical issues, pre-analytical issues with site selection and interface with results for the correct patient being available to caregivers are important influencers on the quality of care being provided. Incorporating meter quality control and the processes for testing and recording values are important components for multidisciplinary committees to consider. Procedures aligned with The Joint Commission (TJC) must be established to assure ongoing quality control of the monitors, process of patient testing and recording the results. Additionally, with such threats to valid POC test results, clinical condition should guide treatment with the use of confirmatory venous samples when in question. Hospitalized patients require frequent testing due to the fluctuations and many variables influencing blood glucose. Testing is generally recommended to be performed before meals and at bedtime in patients who are eating or receiving bolus tube feeds13 although recent studies have called into question the value of the bedtime value.22 In patients who are NPO or receiving continuous enteral or parenteral nutrition, glucose monitoring is performed every four to six hours depending on whether short-acting or rapid-acting analog insulin is used. For patients on intravenous insulin, the ADA and AACE recommend hourly blood glucose monitoring except for patients with stable blood glucose within the target range, for whom monitoring can be performed up to every two hours.
In 2001, van den Berghe published results demonstrating significant improvements in mortality in surgical ICU patients treated with IV insulin therapy targeted at normalizing blood glucose.23 Following this, numerous specialty organizations published recommendations targeting “very tight” glycemic control and many hospitals implemented infusion protocols to normalize blood glucose values in their critically ill patients.24,25 However, subsequent trials had mixed results and finally NICE SUGAR ultimately demonstrated increased mortality and hypoglycemia with “very tight”/normalized blood glucose versus moderate control.26, 27 Revised guidelines now recommend that insulin therapy be initiated if the blood glucose is >180 mg/dL and then maintained between 140 and 180 mg/dL in critically ill patients. Glucose targets somewhat lower than these may be appropriate in selected patients although strong evidence is lacking. The Society of Critical Care Medicine guidelines continue to recommend a target of 100-150 mg/dL but emphasize avoiding hypoglycemia.28 For these purposes, critical illness generally refers to patients requiring invasive mechanical ventilation, those requiring pressor support and patients with multisystem organ failure.
For post-operative cardiovascular surgery, The Joint Commission’s Surgical Care Improvement Project (SCIP) updates from January 2014 set targets of blood glucose levels in the 18-24 hour window after anesthesia end time of <180mg/dL; but these SCIP glycemic metrics are currently on hold as of early 2015 with new metrics still to be determined at the time of this publication.29
With very few prospective, RCT data for establishing specific guidelines in non-critically ill patients, the ADA/AACE recommendations in 2009 are based on clinical experience and judgment.13
Hypoglycemia has associated risks demonstrated in various studies, and strategies are necessary to avoid it. Studies have used variable definitions for hypoglycemia but the ADA has defined hypoglycemia as a blood glucose level <70 mg/dL and severe hypoglycemia as <40 mg/dL.30
Inpatient hyperglycemia is best managed with insulin only. Insulin works reliably, and doses can be rapidly adjusted depending on changes in glucose levels and food intake. Oral agents should be discontinued during acute illness in most circumstances.13 Most are associated with some risks and are limited in their ability to be rapidly adjusted to achieve goals.31, 32
- are NPO on no nutritional replacement
- are on new or tapering steroids
- hypoglycemic risk factors including but not limited to end-stage liver or kidney disease, -
elderly patients or those with an unknown drug overdose
The general recommendations for dosing subcutaneous insulin are derived from published studies and current ADA/AACE and Endocrine Society guidelines. They generally involve:
Following resolution of their indication for insulin infusion, patients will need to be transitioned to subcutaneous insulin. Patients with type 1 DM, on insulin prior to admission to the hospital and those requiring insulin infusion rates more than two units/hour, will need to be transitioned to basal/bolus insulin regimens. The average infusion rate over the preceding six to eight hours is then multiplied by 24 to determine the predicted requirement for the next day. Given that patients are likely to be continuing to improve and have reduced insulin requirements, that daily estimate is further reduced to 60-80 percent. This value can be used as the total daily requirement if they were receiving significant nutritional support in the ICU (TPN or tube feeds) or the basal amount with nutritional layered over time as oral intake increases.35-40
Preparation for transition to the outpatient setting is an important goal of inpatient diabetes management and begins with the hospital admission. The HbA1C is an important laboratory test that should be ordered in nondiabetic hyperglycemic patients and diabetic patients who have not had a recent test. An HbA1c value >6.5% is diagnostic of diabetes, 5.7-6.4% is “pre-diabetes” and one over 9 percent has been recommended by some to indicate the need for newly aggressive treatment strategies.41 Modification of the outpatient regimen should be done with careful planning and assessment of patient and facility-specific resources as well as with communication with the outpatient provider.42 There are several published algorithms for diabetes treatment that can be used to guide such decisions but it is most important to factor in individual patient needs.47 All patients with diabetes should receive teaching in diabetes self-management education focused on survival skills.13
Communication to the outpatient provider regarding the education provided, relevant lab values including the HbA1c and medication changes is essential for patient safety and a requirement of The Joint Commission’s Inpatient Diabetes Disease Certification.
1 Centers for Disease Control and Prevention 2014 National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States. Atlanta: U.S. Department of Health and Human Services. Available at http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf Accessed on May 20, 2015.
2 Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002 Mar; 87:978–982.
3Fraze T, Jiang HJ, Burgess J. Hospital stays for patients with diabetes, 2008. AHRQ Healthcare Cost and Utilization Project. Statistical Brief #93. August 2010. Available from http://www.hcup-us.ahrq. gov/reports/statbriefs/sb93.pdf. Accessed May 15, 2015.
4Newton CA, Young S. Financial implications of glycemic control: results of an inpatient diabetes management program. Endocr Pract. 2006;12(Suppl 3).43–48
5 Center for Medicare and Medicaid Services Hospital-Acquired Condition (HAC) Reduction Program. Available at http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/AcuteInpatientPPS/ HAC-Reduction-Program.html. Accessed May 2015.
6Hellman R. A systems approach to reducing errors in insulin therapy in the inpatient setting. Endocr Pract. 2004;10(suppl 2):100–108.
7Hellman R. Patient safety and inpatient glycemic control: translating concepts into action. Endocr Pract. 2006; 12(suppl 3):49–55.
8Bersoux S, Cook CB, Kongable GL, Shu J. Trends in glycemic control over a 2-year period in 126 U.S. hospitals. J Hosp Med. 2013;8:121–125.
9Swanson CM, Potter DJ, Kongable GL, Cook CB. Update on inpatient glycemic control in hospitals in the United States. Endocr. 2011; Pract 17:853–861.
10 Maynard G, Ramos P, Kulasa K, Rogers KM, Messler J, Schnipper JL, How Sweet Is It? The Use of Benchmarking to Optimize Inpatient Glycemic Control, Diabetes Spectrum. Volume 27, Number 3, 2014.
11 Qaseem A, Humphrey L, Chou R, Snow V, Shekelle P. Use of Intensive Insulin Therapy for the Management of Glycemic Control in Hospitalized Patients: A Clinical Practice Guideline from the American College of Physicians. Ann Intern Med. 2011; 154:260–267.
12 Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, Inzucchi SE, Ismail-Beigi F, Kirkman MS, Umpierrez GE. American Association of Clinical Endocrinologists, American Diabetes Association: American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. 2009; 32:1119–1131.
13 Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, Seley JJ, van den Berghe G, Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97:16–38.
14 Umpierrez GE, Smiley D, Zisman A, Prieto LM, Palacio A, Ceron M, Puig A, Mejia R. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007; 30(9):2181–2186.
15 Umpierrez GE, Hor T, Smiley D, Temponi A, Umpierrez D, Ceron M, Munoz C, Newton C, Peng L, Baldwin D. Comparison of inpatient insulin regimens with detemir plus aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. J Clin Endocrinol Metab. 2009; 94:564–569.
16 Umpierrez GE, Hor T, Smiley D, Temponi A, Umpierrez D, Ceron M, Munoz C, Newton C, Peng L, Baldwin D. Comparison of inpatient insulin regimens with detemir plus aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. J Clin Endocrinol Metab. 2009; 94:564–569.
17Robbins JM, Webb DA. Diagnosing diabetes and preventing rehospitalizations: the urban diabetes study. 2006; 44:292–296.
18Inoue S, Egi M, Kotani J, Morita K: Accuracy of blood-glucose measurements using glucose meters and arterial blood gas analyzers in critically ill adult patients: systematic review. Crit Care. 2013; 17:R48.
19Slater-MacLean L, Cembrowski G, Chin D, Shalapay C, Binette T, Hegadoren K, Newburn-Cook C. Accuracy of glycemic measurements in the critically ill. Diabetes Technol Ther. 2008; 10:169–177.
20 Food and Drug Administration: Blood glucose monitoring test systems for prescription point-of-care use. Available from http:// DeviceRegulationandGuidance/GuidanceDocuments/ UCM380325.pdf. Accessed May 20, 2015.
21 Food and Drug Administration: Self-monitoring blood glucose test systems for over-the-counter use draft guidance for industry and Food and Drug Administration staff. Available from http://www.fda.gov/downloads/ MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/UCM380327.pdf. Accessed May 20, 2015.
22 Vellanki P, Bean R, Oyedokun FA, Pasquel FJ, Smiley D, Farrokhi F, Newton C, Peng L, Umpierrez GE. Randomized controlled trial of insulin supplementation for correction of bedtime hyperglycemia in hospitalized patients with type 2 diabetes. Diabetes Care. 2015; Apr;38(4):568–74.
23 Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive Insulin Therapy in Critically Ill Patients, N Engl J Med. 2001; 345:1359–1367.
24 Clement S, Braithwaite SS, Magee MF, Ahmann A, Smith EP, Schafer RG, Hirsch IB. American Diabetes Association Diabetes in Hospitals Writing Committee: Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004; 27:553–591.
25 Garber AJ, Moghissi ES, Bransome ED Jr, Clark NG, Clement S, Cobin RH, Furnary AP, Hirsch IB, Levy P, Roberts R, Van den Berghe G, Zamudio V; American College of Endocrinology Task Force on Inpatient Diabetes Metabolic Control: American College of Endocrinology position statement on inpatient diabetes and metabolic control. 2004; Endocr Pract. 10:77–82.
26 Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, Dhaliwal R, Henderson WR, Chittock DR, Finfer S, Talmor D. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009; 180:821–827.
27The NICE-SUGAR Study Investigators. Intensive versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med. 2009; 360:1283–1297.
28 Jacobi J, Bircher N, Krinsley J, Agus M, Braithwaite SS, Deutschman C, Freire AX, Geehan D, Kohl B, Nasraway SA, Rigby M, Sands K, Schallom L, Taylor B, Umpierrez G, Mazuski J, Schunemann H. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med . 2012; 40:3251–3276.
29Surgical Care Improvement Project. Available at at http://www.jointcommission.org/assets/1/6/2w_SCIP-Inf-4.pdf. Accessed May 2015.
30 Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013 May; 36(5):1384–1395.
31Deusenberry CM, Coley KC, Korytkowski MT, Donihi AC. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy. 2012; 32:613– 617.
32 Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010; 1:CD002967.
33Kavanagh BP, McCowen KC. Clinical practice: glycemic control in the ICU. N Engl J Med. 2010; 363:2540 –2546.
34 Ku SY, Sayre CA, Hirsch IB, Kelly JL. New insulin infusion protocol improves blood glucose control in hospitalized patients without increasing hypoglycemia. Jt Comm J Qual Patient Saf. 2005; 31:141–147.
35 Bode BW, Braithwaite SS, Steed RD, Davidson PC. Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy. Endocr Pract. 2004; 10 (Suppl. 2):71–80.
36Furnary AP, Braithwaite SS. Effects of outcome on in-hospital transition from intravenous insulin infusion to subcutaneous therapy. Am J Cardiol. 2006; 98:557–564.
37Olansky L, Sam S, Lober C, Yared JP, Hoogwerf B: Cleveland Clinic cardiovascular intensive care unit insulin conversion protocol. J Diabetes Sci Technol 3:478– 486.
38 Schmeltz LR, DeSantis AJ, Schmidt K, O’Shea-Mahler E, Rhee C, Brandt S, Peterson S, Molitch ME. Conversion of intravenous insulin infusions to subcutaneously administered insulin glargine in patients with hyperglycemia. Endocr Pract. 2006; 12:641– 650.
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domain: literature


text:
'I swear to tell the truth, the whole truth, and nothing but the truth' we say in a court of law. 'In a court of law, the truth is precisely what we will not say', says Lacan. 'If God is dead, everything is permitted', writes Dostoyevsky. 'If God is dead, everything is prohibited', responds Lacan. 'I think, therefore I am', reasons Descartes. 'I am where I do not think', concludes Lacan. What are we to make of Lacan's inversions of these mottos? And what are the implications for the legal system if we take them seriously? This book puts the legal subject on the couch and explores the incestuous relationship between law and desire, enjoyment and transgression, freedom and subjection, ethics and atheism. The process of analysis problematizes fundamental tenets of the legal system, leading the patient to rethink long-held beliefs: terms like 'guilt' and 'innocence', 'truth' and 'lies', 'reason' and 'reality', 'freedom' and 'responsibility', 'cause' and 'punishment', acquire new and surprising meanings. By the end of these sessions, the patient is left wondering, along with Freud her analyst, whether 'it is not psychology that deserves the mockery but the procedure of judicial enquiry'.
A unique study on the nexus of Law and Psychoanalysis, this book will interest students and scholars of both subjects, as well as general readers looking to explore this perverse and fascinating relationship.