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A romantic hike can be a great way to spend some quality time together. First, plan your route ahead of time and choose one that has plenty of scenic views. Bring a picnic lunch or snack to enjoy in a peaceful spot along the way.
Pack items like candles, blankets and music so that you can create an intimate atmosphere when you reach your destination. When you do get there, take the opportunity to talk about meaningful things such as dreams and aspirations for the future. Finally, don’t forget to take lots of pictures!
This will help preserve those special moments for years to come.
- Find a scenic spot: Choose a spot for the date that offers beautiful views and pleasant surroundings
- Consider hiking to a lookout point or waterfall, or any other natural area with stunning scenery
- Pack a picnic lunch: Add some romance to your hike by packing a romantic picnic lunch with all of your partner’s favorite foods or snacks
- You can even add in some treats like chocolate-covered strawberries to make it extra special! 3
- Bring along music: Create an intimate atmosphere on the hike by bringing along portable speakers and playing romantic music while you walk together in nature
- Utilize the sunset: Watch the sun set together at an elevated viewpoint during your hike for added intimacy and romance between you two lovebirds!
How Can I Make My Hiking Date More Fun?
Hiking dates are an excellent way to explore nature and take in the beauty of your surroundings while also spending quality time with someone special. To make your hiking date more enjoyable, consider bringing along some snacks to enjoy during breaks from walking, such as trail mix or fresh fruit. Additionally, plan ahead by researching the hike beforehand so that you know what kind of terrain and other obstacles you may encounter; doing this will ensure a hassle-free experience for both of you.
Furthermore, don’t forget to bring plenty of water – staying hydrated is key when engaging in physical activity like hiking! Finally, instead of focusing on reaching a certain destination or goal – focus more on enjoying each other’s company throughout the journey. This could involve playing games together (like I Spy!), having meaningful conversations about life goals or interests, and taking lots of photos together along the way.
With these tips in mind – your next hiking date is sure to be fun-filled and memorable!
Can a Hike Be Romantic?
A hike can be a perfect way to spend quality time together with your partner and make it an incredibly romantic experience. The beauty of nature, the fresh air, the stunning views at the destination – all these will help you create unforgettable memories. Don’t forget to take some snacks and drinks along so you can have a picnic on top of the mountain or in a peaceful meadow.
If you’re feeling adventurous enough, why not plan something special? For example, set up candles around your camping spot for dinner and put on some music for atmosphere. Or surprise your better half by bringing flowers or writing him/her love poems that express how much he/she means to you.
You don’t need expensive gifts or restaurants; just being present with each other is enough!
Is Going on a Hike a Good Date?
Going on a hike is an excellent idea for a date! It’s not only incredibly romantic, but it also provides the perfect opportunity to bond with your loved one and enjoy nature at its best. Not only can you get some fresh air and exercise, but you can also take in the scenery around you.
On top of that, the conversation flows much easier when walking side-by-side than sitting across from each other in a restaurant or bar. You’ll have plenty of time to talk about whatever comes up so you can really get to know each other better. Plus, if things go well there’s always the possibility of ending off your day with dinner or drinks afterwards – something extra special that will make your date even more memorable.
All in all, going on a hike is definitely an excellent way to spend quality time together!
What Should I Bring on a Hiking Date?
If you’re planning on going on a hiking date, it’s important to make sure you have the right gear. One of the most important things to bring is plenty of water; even if your hike isn’t particularly long or strenuous, being out in nature can take its toll and dehydration can set in quickly. Make sure to also bring some high-energy snacks like granola bars or trail mix that will help keep up your energy levels throughout the day.
Additionally, don’t forget sun protection! A hat and good sunscreen are essential for any outdoor activity since UV rays reflect off of rocks and trees during hikes more than they do at other times. Finally, it’s always a good idea to dress appropriately – wear layers so that when you get hot while climbing uphill, you can peel them off one by one as needed without getting too cold when you stop for breaks (but make sure not to leave anything behind!).
With these items packed away safely in your backpack, there’s nothing stopping you from having an amazing time on your hiking date!
ChatGPT | 5 Romantic Hiking Date Ideas for Nature Enthusiasts
Hiking Date Outfit
When planning what to wear for a hiking date, it’s important to be comfortable and prepared. Choose clothing that is breathable and won’t restrict your movement while you’re out on the trail. A good outfit might include lightweight layers like a t-shirt or tank top paired with shorts or leggings, a hat to block the sun, and some sturdy footwear like sneakers or hiking boots.
Remember to bring along sunscreen (especially if you’ll be in direct sunlight) and carry plenty of water bottles so you stay hydrated throughout the hike!
Hiking Date near Me
If you’re looking for a great way to spend quality time with your significant other, why not take a hiking date near you? There are plenty of trails and parks in your area that offer beautiful scenery, fresh air, and the chance to explore nature together. Plus, it’s a great opportunity to get some exercise while having fun!
You can find local hikes on websites like AllTrails or check out your local park system website for recommendations.
Is Hiking a Date Or Hanging Out
Hiking on a date can be both enjoyable and rewarding. It’s an activity that allows you to explore nature while spending quality time with your partner. Whether it’s an afternoon stroll at a nearby park or a longer trek through the woods, hiking is great way to get outside and enjoy each other’s company.
So if you’re looking for something different to do with your significant other, why not try hitting the trails?
Hike Date Means
A hike date is a great way to spend time outdoors with your significant other. Whether it’s an afternoon stroll through the woods or a day-long journey up and down mountains, you can experience nature together in stunning locations around the world. Hiking provides ample opportunity for conversation, exercise and exploration of new places, making it an ideal activity for couples looking to deepen their bond while having fun.
A romantic hiking date can be a great way to spend quality time with your partner. With the right planning and preparation, you can make sure that it’s an experience for both of you to remember fondly. Whether you opt for a scenic trail or something more challenging, there are plenty of ways to add some romance and excitement to your excursion.
Enjoy the beauty of nature together as well as each other’s company on this special outing!


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- Research article
- Open Access
PK/PD modeling of Ceftiofur Sodium against Haemophilus parasuis infection in pigs
BMC Veterinary Research volume 15, Article number: 272 (2019)
Ceftiofur Sodium is widely used in China. Our aim was to determine Ceftiofur Sodium activity and optimize dosing regimens against the pathogen Haemophilus parasuis using an in vitro and ex vivo pharmacokinetics/pharmacodynamics modeling approach. By adopting these strategies, we wanted to extend the effective life of Ceftiofur Sodium in reduce drug-resistance in pigs.
We established an H. parasuis infection model in pigs, and assessed the pharmacokinetics of Ceftiofur Sodium in both healthy and infected animals. After Ceftiofur Sodium (10 mg/kg, i.m.) administration to healthy and H. parasuis-infected pigs, plasma based desfuroylceftiofur (a metabolite of Ceftiofur Sodium) was measured by High Performance Liquid Chromatography. The pharmacokinetics of Ceftiofur Sodium (desfuroylceftiofur) was consistent with a two-compartment open model, with first-order absorption. We observed no significant differences (P > 0.05) in pharmacokinetic parameters between healthy and infected pigs. Pharmacodynamics data showed that Ceftiofur Sodium was highly inhibitory against H. parasuis, with MIC, MBC, and MPC values of 0.003125, 0.0125 and 0.032 μg/mL, respectively. Desfuroylceftiofur in plasma also had strong bactericidal activity. Almost all H. parasuis cultured in plasma medium of Ceftiofur Sodium-inoculated healthy pigs, at each time point, were killed within 24 h. A weaker antibacterial activity was measured in infected-pig plasma medium at 18, 24, 36, and 48 h, after Ceftiofur Sodium inoculation. Pharmacokinetic parameters were combined with ex vivo pharmacodynamic parameters, and the bacteriostatic effect (36.006 h), bactericidal effect (71.637 h) and clearance (90.619 h) within 24 h, were determined using the Hill equation. Dose-calculation equations revealed the optimal dose of Ceftiofur Sodium to be 0.599–1.507 mg/kg.
There were no significant differences in Ceftiofur Sodium pharmacokinetic parameters between healthy and infected pigs, although pharmacokinetics/pharmacodynamics fitting curves showed obviously differences. The optimal dose of Ceftiofur Sodium was lower than recommended (3 mg/kg), which may provide improved treatments for Glässers disease, with lower drug-resistance possibility.
Globally, Glässers disease (GD) is a fatal swine disease, and is one of the main causes of nursery pig deaths on large-scale farms [1,2,3]. The disease is characterized by fibrinous polyserositis, polyarthritis, meningitis and acute pneumonia (without polyserositis) [4, 5], and is associated with high morbidity and mortality [1, 6]. GD is caused by a gram-negative bacillus Haemophilus parasuis  which is an opportunistic pathogen residing in the nasal and oral cavities of most pigs. The bacillus is primarily benign [7, 8], however it causes disease when pigs become stressed .
Antimicrobials have been used to treat GD, however this causes drug resistance due to the widespread, non-standard use of drugs on intensive pig breeding farms . Additionally, several H. parasuis genes, resistant to multiple antimicrobials, have been identified in this pathogen [10,11,12,13,14,15,16,17]. When high development costs, safety risks and rapid pathogen resistance to new drugs are all considered, it is advantageous to exploit existing antibacterial drugs by designing optimal treatments to avoid pathogen exposure to sub-lethal drug concentrations [18, 19].
Ceftiofur Sodium (CS) is an animal-specific, third-generation cephalosporin, widely used in China and abroad for its activity against most Gram-negative and some Gram-positive bacteria [20,21,22]. It is rapidly metabolized to desfuroylceftiofur (DFC) upon intravenous injection. It has been shown that CS and DFC have similar activities against Gram-negative bacteria, with minimum inhibitory concentrations (MIC) differing by less than one dilution factor . Studies have been conducted on the pharmacodynamics (PD) of CS to some pathogens like Klebsiella pneumonia and Staphylococcus aureus . Similarly, the pharmacokinetics (PK) of CS has also been reported in swine and calves [25,26,27]. PK and PD data has also been generated for CS activities in goat, against Mannheimia haemolytica and Pasteurella multocida [28, 29], and in cattle against Escherichia coli . However, PK/PD modeling of CS against H. parasuis has not yet been studied.
According to the relationship between PK and PD, a reasonable dosing drug regimen can be established to maximize clinical efficacy and to minimize the selection pressures of bacterial resistance and the spread of drug-resistant pathogens [31,32,33]. The ex vivo model uses plasma or tissue percolates collected over a time series after drug administration (oral, intravenous or intramuscular injection) instead drug solution of directly in vitro PD measurement. Combined with in vivo PK measurements, a corresponding dosing regimen can be more rationally formulated.
In this study, PK/PD parameters of CS activity against H. parasuis were explored through the ex vivo PD parameters of CS and in vivo PK parameters. Differences in PK parameters between healthy and infected pigs were also compared, and a corresponding dosing regimen proposed, which we wish to help exert best therapeutic effect, reduce prevalence of bacterial resistance, and prolong the lifespan of CS in the clinic.
Growth curve of H. parasuis in TSB medium
As shown in Fig. 1, H. parasuis growth in TSB medium conformed to the logistic growth model. The exponential period was at approximately 6–16 h, and the T1/2K was at approximately 12 h.
Symptoms of H. parasuis infection
After a 2–4 h inoculation, piglets experienced increased body temperatures, vomiting, runny noses, depression, reduced appetites, difficulty in breathing, redness of skin, messy coat hair, muscle tremors, instability on their legs (followed by lameness), slight cyanosis in the nose, ear tip and limbs ending, orbital edema and ataxia. These symptoms indicated that the H. parasuis infection model had been established.
The PK of CS in healthy and infected piglets
Specificity tests showed that the DFC peak was at approximately 13.5 min, with no interference impurity peak nearby. This method also had a high precision (intra-day RSD < 4.10% and inter-day RSD < 8.92%) and DFC recovery (91.07–94.48%). A standard curve was established; y = 0.7183x - 0.05117 (where y: Response (mA·min), x: DFC concentration (μg/mL)) with R2 = 0.9995.
As shown in Fig. 2, DFC concentrations were measured at different times, in both healthy and infected pigs. DFC concentrations changed similarly between healthy and infected groups, and there were no significant differences (P > 0.05) between healthy and infected groups, at each time point. However, DFC concentrations in infected pigs increased a little faster than in healthy pigs.
Analyses by WinNonlin, using the Atrioventricular Model, showed that the PK of CS (DFC) after intramuscular injection was consistent with a two-compartment open model, with first-order absorption. The main PK parameters are shown in Table 1, after curve fitting. These parameters showed the same patterns as with measurement curves. There were no significant differences between the PK parameters of the infected group and the healthy group (P > 0.05), suggesting that the PK of CS in these groups were similar.
The PD of CS in H. parasuis
CS strongly inhibited H. parasuis, with a CS MIC of 0.03125 μg/mL in TSB medium. The MBC and MPC were 0.0125 and 0.0320 μg/mL, respectively. We also obtained results from plasma medium; MIC and MBC in plasma medium were 0.00625 and 0.0250 μg/mL, respectively.
As shown in Fig. 3, bacterial densities decreased rapidly after CS addition, at a density above (and including) the MIC. Similarly, bacterial densities decreased for a long time with dropping slopes. These observations indicated that CS had long term inhibitory effect against Parasuis, but these effects gradually diminished over time, suggesting CS inhibition of Parasuis was in part dose-related.
The PAE of CS in H. parasuis increased gradually with increasing CS concentrations, but the degree of enhancement was weak. PAE were 1.06, 1.12, and 1.46 in 1, 2, and 4 MIC, respectively.
In vitro bactericidal curves, at different time points, are shown in Figs. 4 and 5. DFC had strong bactericidal activity in the plasma of healthy pigs (Fig. 4). Almost all bacteria were killed after 24 h of culture, with the 48-h sample exhibiting weak antibacterial activity. Plasma samples from infected pigs had weaker antibacterial activity at 18, 24, 36, and 48 h (Fig. 5). This indicated that the DFC activity was different between healthy and infected pigs, although PK data were similar between the groups.
The establishment of a PK/PD model and dosing regimen
The PK/PD parameters describing the bactericidal effects of CS against H. parasuis are reflected by AUC/MIC values. Specifically, when plasma was inoculated with bacteria at different time points, the mean ex vivo value of AUC/MIC was the product of the culture time and diluted concentration as the indirect in vivo AUC divided by the MIC measured in vitro. WinNonlin was used to fit ex vivo PD data and PK/PD parameters into the Sigmoid Emax model (the Hill equation) (Figs. 6 and 7) to show the relationship between ex vivo AUC24 h/MIC and antibacterial efficacy (Table 2). The effects of CS were established in healthy pigs more quickly than the infected group (Figs. 6 and 7). CS exhibited a similar bacterial inhibition at different degrees, with bacteriostatic action at 28.406 h, bactericidal action at 29.516 h, and bacteriophagous action at 29.913 h. However, bacterial inhibition was different in infected pigs, with bacteriostatic action at 36.006 h, bactericidal action at 71.637 h, and bacteriophagous action at 90.619 h (Table 2). When the AUC24 h/MIC reached 90.619 h, H. parasuis was eliminated (the parameter values of CS to achieve antibacterial effects refer to the PD data of healthy pigs, and the parameter values that achieved sterilization effects refer to the PD data of infected pigs). By fitting the Hill equation to infected pig data, dose-calculation equations revealed the optimal dose of CS to be 0.599–1.507 mg/kg.
The determination of dosing regimens for sick piglets is primarily based on PK data of reference drugs in healthy pigs. However, the absorption, distribution and metabolism of drugs are different between healthy and diseased animals, and so too is the response of animals to these drugs. These differences can cause changes in PK characteristics of drugs in animals, however traditional formulation methods do not consider these changes in diseased animal physiology . Drug regimens will become more accurate and effective if PK differences between healthy and diseased animals are determined.
H. parasuis mainly infects pigs aged between 2 and 16 weeks (especially piglets aged 5–8 weeks). In the present study, 6-week-old nursery pigs were selected to test the infection characteristics of H. parasuis. The inoculation dose in our model was 3.0 × 109 CFU/mL, with pig mortality reaching 50% after 4 h, similar to Wang et al. . In their study, mortality reached 40% upon intraperitoneal inoculation with 3.4 × 109 CFU/mL of the H. parasuis S4 strain. At 2–4 h post inoculation, the symptoms of vaccinated pigs were similar to those of pigs infected with H. parasuis, as noted by Yin et al.  and Oliveira et al. . Plasma from both healthy and infected pigs was the main (convenient and fast) reagent for ex vivo testing [29, 38, 39], however, other materials, like ileum content , were also previous used, which depends on the action site of the pathogen.
We investigated the PK characteristics of CS (10 mg/kg, i.m.) in pigs infected with H. parasuis, and also healthy pigs. The PK of healthy and infected pigs corresponded to a two-compartment open model, with first-order absorption. The peak CS concentration reached 11.236 μg/mL at 2.358 h in healthy pigs, the absorption half-life was 1.517 h, the elimination half-life was 17.550 h, and the AUC was 125.646 h·μg/mL. These data are different to Hu et al. , and may due to the pig’s age, the dose administered (10 mg/kg in this study but 5 mg/kg in Hu et al. ) or different analysis software.
PK differences between healthy and infected pigs were not significant (P > 0.05), suggesting that the time, speed, degree, bioavailability and distribution of CS in healthy and infected pigs were not significantly different. Similarly, Zhang et al.  analyzed the PK of tilmicosin in both healthy and H. parasuis infected pigs, and found no significant differences between the PK profiles in the two groups. However, Gao et al.  observed leukopenia and hypoglycemia in H. parasuis-infected pigs, with varying degrees of injury to liver and kidney. These conditions change the distribution, absorption and elimination of the drug in a pigs’ body . Our study showed some differences to Gao et al. , possibly because: (i) PK observations were performed a short time after artificial infection with H. parasuis and (ii) in our study H. parasuis did not cause similar kidney and liver damage.
For a time-dependent drug, the time that CS concentrations were above the MIC (T > MIC) should be well determined in its PK/PD modeling. However, plasma concentrations in the in vitro tests were constant, such that T > MIC is hardly to be accurate. According to the CS curve against H. parasuis, we found an obvious time depending inhibition activity same with a partly concentration-dependent pattern (Fig. 3), for which the AUC24 h/MIC as a suitable PK/PD parameter for CS . For drugs like CS and other β-lactam antimicrobials, the key to their antibacterial effectiveness is their effective duration (i.e., T > MIC). Combined with mutant selection window theory (MSW theory; drug resistance is more likely to occur between MSWs), it is conducive to reducing drug resistance when we increase its concentration initially and keep it above MPC for a certain time. In the present study, bacteriostatic, 99.9% killing and 99.99% killing (completely sterilized without leading resistance) concentration of CS is 0.599, 1.191, 1.507 mg/kg and the recommended dosing regimen for CS was 0.599 mg/kg for prophylactic injection in healthy pigs and 1.507 mg/kg for pigs with symptoms. This regimen was different to the observations of Li et al.  and Chen et al.  who recorded a 5 mg/kg CS for a single dose, and also less than 3 mg/kg (suggested in prescription), which had sufficient inhibitory effects against Streptococcus, Pasteurella and Actinobacillus species. The reason for this may have been differences in age and body weight of pigs, and in the formulation of the drug-delivery plan. Equally, a standard H. parasuis strain was selected as the test strain; the CS MIC of this strain was extremely low, suggesting that the recommended dosing regimen may not be suitable for highly resistant strains.
In summary, our study provides a basic rational dosing regimen, but our PK/PD model mainly targets the antibacterial effects of CS. Antibacterial effects also include immune functions and defense capabilities . The AUC of our PK/PD model was the product of drug concentrations and cultures at different time points. CS degradation in plasma was not considered. The H. parasuis strain used in our study was a standard strain, not a clinical-isolate strain. Therefore, CS was more sensitive to the MIC of H. parasuis, and the PK/PD parameters may have varied due to H. parasuis in the body. Therefore, our results should be used only for guidance in clinical dosing.
This study suggests that CS strongly inhibits H. parasuis with low MIC, both serum and TSB broth, and PK of CS was consistent with a two-compartment open model with first-order absorption. There were no significant differences in PK parameters between healthy and infected pigs, however the PK/PD fitting curve showed obvious differences. The optimal CS dose was calculated at 0.599–1.507 mg/kg per day, which may be used as a guidance in clinical practice.
Test strains, animals and drugs
The standard strain of H. parasuis (SW124, serotype 4, isolated from a pig farm in Jianwei, Sichuan Province, China ) and Enterococcus faecalis (ATCC29212, quality control) were purchased from the China Institute of Veterinary Drug Control (Beijing, China). Bacterial strains were stored − 80 °C in tryptone soy broth medium (TSB medium) supplemented with 25% glycerol. They were recovered in TSB medium at 37 °C. Modified TSB medium and tryptone soy agar medium (TSA medium) supplemented with 5% bovine plasma and 10 μg/mL (final concentration) NAD+ were used in all tests. Strain cell density was measured by two approaches; Mcfarland standards and absorbance at OD600nm, where an optical density of 0.08–0.10 equated to approximately 1.0 × 108 CFU/mL.
Twenty healthy Duroc × Landrace × Yorkshire three-way crossbred piglets were used for tests. All piglets (provided by Youlike Agriculture and Animal Development Co., Ltd. in Fujian Province, China) were of similar age (six weeks old) and similar physical status (mean body weight 14.96 ± 0.47 kg) and were antimicrobial free. Piglets were divided randomly (piglets were blindly numbered and randomly divided by Excel) into a control (n = 8) group and test (n = 6 × 2) groups . Piglets were housed on a farm and fed a normal diet and water, free of antimicrobials. They were observed for one week before experimental procedures. Euthanasia procedures were performed by the administration of pentobarbital sodium (intravenously) at study end. The test farm was free of H. parasuis infection. The study was approved by the Research Ethics Committee of College of Animal Science, Fujian Agriculture and Forestry University (No. PZCASFAFU2018001).
A High-performance liquid chromatography (HPLC) CS standard (batch number 104666, with a purity over 98%) and a DFC (1-LLH-29-2) standard were obtained from Dr. Ehrenstorfer GmbH (Augsburg, Germany), while the TRC standard came from elsewhere (Lowell, MA, USA). CS powder for injection (batch number DVK170504) was purchased from Hebei Yuanzheng Pharmaceuticals (Hebei, China). The methods described herein were modified from Huang et al.
Growth curves of H. parasuis in TSB medium
100 μL H. parasuis growth medium (OD600 = 0.08–0.10) was transferred to 100 mL TSB medium and cultured at 37 °C, at 190 rpm. Every two hours, approximately 1 mL culture medium was collected and the OD600nm measured to generate a growth curve of H. parasuis in TSB medium, by which harvested time was determined.
The PK of CS in healthy and infected piglets
Piglet infection, drug administration and sampling
Exponentially growing bacteria were diluted to a McFarland turbidity of 10 (~ 3.0 × 109 CFU/mL) in TSB, with 1 mL injected (i.p.) into each piglet. After injection, rectal temperatures and other clinical observations were monitored, e.g., vomiting, lameness, appetite loss, respiration rates and mental state.
10 mg/kg body weight of CS was injected (i.m.) into all piglets at 4 h after bacteria injection. Approximately 3 mL of blood was collected from the anterior vena cava before administration (0 h time-point) and later at 15 min, 40 min and 1, 1.5, 2, 3, 5, 7, 10, 14, 18, 24, 36, and 48 h post CS injections. Blood was immediately transferred to heparin tubes containing anticoagulant and mixed. Bloods were centrifuged at 2000 g 4 °C for 5 min and the resulting plasma supernatant was stored at − 20 °C.
CS plasma concentrations
DFC concentrations were measured by HPLC using the method from Li et al.  to represent CS plasma concentrations, as CS is rapidly metabolized to DFC in test animals.
Extraction: 0.5 mL plasma was mixed with 7 mL of 0.4% DTE-borate buffer. The mixture was incubated for 15 min at 50 °C in a water bath, with a 10 s vortexing every 3 min. Samples were then centrifuged after cooling to 25 °C, and the supernatant was collected.
Solid phase extraction: An Agilent C18 column (100 mg/3 cc) was activated and equilibrated consecutively with 3 mL methanol and ultrapure water. Extracted materials were added to the C18 column and a flow rate set at 1 mL/min. The column was then eluted with 6 mL methanol, after which the eluate was concentrated by nitrogen-blow at 45 °C. The concentrated solution was vortexed with 0.5 mL 0.01 mol aqueous ammonium solution, sonicated for 5 min, filtered through a 0.22 μm filter and prepared to test. The DFC standard was added to 0.5 mL plasma (to achieve final concentrations of 0.025, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, and 20.0 μg/mL) and prepared with same process as samples from test groups.
HPLC: Samples were measured at 266 nm on an Agilent ZORBAX Eclipse XDB-C18 (4.6 × 150 mm, 5 μm), using a mobile phase of acetonitrile and 0.1% trifluoroacetic acid, at 1 mL/min as described by Li et al. . Specificity was tested using a standard DFC solution (water), blank plasma and a standard DTE solution (blank plasma). Precision and recovery were tested using 0.25, 5.0, 20.0 μg/mL standard DTE solutions (blank plasma) five times on different days, with five repeats for each concentration. A standard DTE curve was generated using 0.025, 0.05, 0.1, 0.25, 0.5, 1.0, 2.5, 5.0, 10.0, 20.0 μg/mL standard DTE solutions (blank plasma).
PD of CS in H. parasuis
MIC, MBC and MPC determination
The CS MIC of H. parasuis was determined using a modified broth micro-dilution method, recommended by the Clinical Laboratory Standards Institute (CLSI; Wayne, PA, USA)  and Zhang et al. . Approximately 100 μL TSB medium or plasma medium containing CS with degrees of 1.5625, 3.125, 6.25, 12.5, 25, 50, 100, 200, 400, and 800 ng/mL were made up in in 96 well plates. To each treatment, 5 μL diluted H. parasuis culture (1.0 × 107 CFU/mL) in the exponential phase was added. A standard E. faecalis (ATCC 29212) served as a quality control and was supplemented with ampicillin at 0.5–2 μg/mL. The 96 well plate was agitated at 190 rpm at 37 °C and observed at 24 and 48 h. The concentration of clear well observed by naked eye was considered as MIC.
To determine the MBC, 100 μL medium (TSB medium and plasma medium) from the clear wells, from the MIC test were spread onto TSA plates, and cultured for 48 h at 37 °C. The minimal concentration of bacteria-free (no colonies on the plate) was considered the MBC.
To determine the MPC, TSA plates were prepared by adding CS at a degree increased by a certain amount from MIC. Exponential growth phase bacteria were pelleted by centrifuging at 3000 rpm at 4 °C. The pellet was then diluted to 3 × 1010 CFU/mL with TSB medium. From this, 100 μL bacterial solution was applied to TSA plates and incubated for 24 h at 37 °C. After this period, all colonies were counted. The CS provisional MPC (MPCpr) was determined as the lowest concentration after 72 h of sterile growth. The same TSA plates series was prepared and acted with a CS degree decreased by 20% from MPCpr, and MPC was determined as the lowest concentration after 72 h of sterile growth (no colony in plate).
In vitro PAE determination
Approximately 1.8 mL exponential phase H. parasuis (1.0 × 108 CFU/mL) was mixed with 0.2 mL CS solution, to generate final concentrations of 1 MIC, 2 MIC and 4 MIC. A 0.2 mL aliquot of physiological saline was used as control. Volumes were cultured in glass tubes and grown for 2 h in 37 °C to induce PAE production. 100 μL cultured medium was mixed with 0.9 mL TSB medium and cultured at 37 °C. 100 μL samples were taken at 0, 1, 2, 4, 6, 8, and 12 h, and diluted to 0.1% in sterile physiological saline to count cells. Each treatment was performed four times. Growth curve for H. parasuis, at different CS concentrations were established, and T (time required for bacterial numbers to be 10 times higher than 0 h in the test groups) and C (time required for the bacterial numbers to be 10 times higher than 0 h in control groups) values were calculated. PAE was calculated as the difference between T and C (PAE = T - C).
In vitro and ex vivo bactericidal curves
To determine in vitro bactericidal curves, exponential growth phase bacteria were diluted to 1.0 × 105 CFU/mL in TSB medium. 1.5 mL of this solution was mixed with 1.5 mL CS solution to generate final concentrations of 1/4, 1/2, 1, 2, 4, 8, 16, and 32-fold MIC in 5 mL glass tubes. 1.5 mL physiological saline was used as 0 MIC. Tubes were incubated at 37 °C for 24 h, with 100 μL removed at 0, 1, 2, 4, 8, 12, and 24 h, and then plated on TSA for colony counting.
To determine ex vivo bactericidal curves, bacteria (1.0 × 105 CFU/mL) were co-incubated with plasma samples from pigs at different CS time points, from piglet sampling. Plasma was prepared by centrifugation (4500 rpm for 5 min), filtered (0.45 μm membrane), inactivated (56 °C for 30 min) and finally filtered (0.22 μm membrane) before being cultured with bacteria at 37 °C for 24 h. 100 μL sample of each treatment was collected at 0, 1, 2, 4, 8, 12, and 24 h, and then applied to TSA plates to count colonies.
Data processing and the establishment of a PK/PD model
The area under the curve at 24 h; AUC24 h/MIC for CS to induce antibacterial and bactericidal effects was determined by fitting a Sigmoid Emax model (the Hill equation) with ex vivo PD and in vivo PK parameters, using WinNonlin® software (SCI Software, Statistical Consultants Inc.). This model is described as:
Emax represents the maximum difference between the logarithmic value of the number of bacteria before and 24 h after CS administration in the blank group; E0 is the maximum difference between the logarithmic value of the number of bacteria in the plasma sample; EC50 represents the 50% PK/PD parameter that produced the greatest antibacterial effect in plasma samples; Ce is the parameter value of different samples; N represents the slope of the equation and determines the steepness of the S-curve.
Predicting the dosing regimen
To calculate the dose needed, the AUC24 h/MIC of different antibacterial effects was substituted into the following formula:
where AUC/MIC is the targeted end point for optimal efficacy; MIC is the minimum inhibitory concentration; CL is the clearance per day; fu is the free fraction of drug in plasma (ignore if minimal binding). The ex vivo antibacterial effects of CS administration were quantified at three levels: (1) bacteriostatic action (no change in bacterial counts, E = 0); (2) bactericidal action (99.9% reduction in bacterial counts, E = − 3); and (3) bacterial elimination (99.99% reduction, E = − 4) .
PD and some PK data were processed using Excel™ (Microsoft, Redmond, WA, USA). Several PK parameters were also calculated using WinNonlin. The PK data for CS in healthy pigs and H. parasuis-infected pigs were analyzed using SPSS v21 (IBM, Armonk, NY, USA).
Availability of data and materials
The datasets during and/or analysed during the current study available from the corresponding author on reasonable request.
High performance liquid chromatography
Minimum bactericidal concentrations
Minimum inhibitory concentrations
Mutant prevention concentrations
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The authors thank the Guoxu Lin for supporting on this study.
This work was financially supported by the grants from the State Key Development Program during the 13th Five-Year Plan period (Grant No.2016YFD0501310). The funding body had no role in the design of the study, collection, analysis, and interpretation of data and in writing the manuscript.
Ethics approval and consent to participate
This study was approved consent to participate by the Research Ethics Committee of College of Animal Science, Fujian Agriculture and Forestry University (No. PZCASFAFU2018001).
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No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication.
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Cite this article
Li, Xd., Chi, SQ., Wu, LY. et al. PK/PD modeling of Ceftiofur Sodium against Haemophilus parasuis infection in pigs. BMC Vet Res 15, 272 (2019). https://doi.org/10.1186/s12917-019-2008-4
- Ceftiofur sodium
- Haemophilus parasuis
- PK/PD model
- Ex vivo bactericidal activity, Glässers disease

domain: biology


text:
This is a reproduction of a book published before 1923. This book may have occasional imperfections such as missing or blurred pages, poor pictures, errant marks, etc. that were either part of the original artifact, or were introduced by the scanning process. We believe this work is culturally important, and despite the imperfections, have elected to bring it back into print as part of our continu...
Paperback: 332 pages
Publisher: Nabu Press (August 17, 2010)
Product Dimensions: 7.4 x 0.7 x 9.7 inches
Amazon Rank: 18812004
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The two appendixes in the back are worth the price of the book. It is divided into four parts and the first three parts is a series of articles. Kinsella and her publisher. To think of anything other than war and death would be too painful. The thing that is most noticeable about Carey's writing compared to almost any other current author I can name is that he is such a fine, literate writer. As a spokesman for aestheticism, he tried his hand at various literary activities: he published a book of poems, lectured in the United States and Canada on the new "English Renaissance in Art" and then returned to London where he worked prolifically as a journalist.
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domain: library


With the change in administrations changes are happening at all state agencies. New leadership. New goals. New priorities. And, as it turns out, new TV channels as well.
Plunderbund has just learned that the Ohio Department of Transportation’s cafeteria, which used to show CNN during the day, has recently been ordered by ODOT’s HR department to ONLY show Fox News (Kasich’s former employer).
First thoughts: is ODOT’s Human Resources paying someone to hang around the TV to yell at you if you change the channel? Did they just post a nasty memo? Or did they just take the cheap route […]Full Story... →
I don’t often agree with Matt Mayer of the Buckeye Institute but his tweet this afternoon was dead on:
Not even the Buckeye Institute, a conservative group that promotes job creation and entrepreneurship, believes Kasich and Kvamme’s lies about transparency and ethics rules hindering the job creation abilities of JobsOhio and the Department of Development.Full Story... →
Today’s JobsOhio hearing is about to start (check Twitter and I’ll update you if anything interesting happens). While you’re waiting I thought you might like to read Mark Kvamme’s testimony from yesterday. (see below)
Some quick notes: It’s very clear from Kvamme’s testimony at the JobsOhio hearing yesterday that he doesn’t know how state government works – and he doesn’t seem to care. This shouldn’t surprise anyone given that the guy who hired him has no clue either. And yet both men are making downright false claims that existing government regulations get in the way of development.
For example, Kvamme […]Full Story... →
This morning, I called the office of Chairman of the House State Government Committee to ask what I needed to do so that I could offer opponent testimony to House Bill 1, Governor Kasich’s JobsOhio initiative.
The gentleman I talked to was very polite, professional, and respectful, but this is what I was told:
I needed to have 50 copies of my prepared testimony and be there today as the committee is scheduled to begin its second day of testimony at 11:00 this morning. I asked that since I just saw a draft of the bill last night and didn’t […]Full Story... →
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Scars Of Life
Scars Of LifeScars of Life is a powerful five-piece groove oriented metal band that emphasizes depth in musical style and emotionally-charged meaning in its lyrics. This quintet hails from South Florida, and is currently taking on the music scene by storm, propelling its music to new heights daily.In the new millennium, Scars of Life was created after the disbanding of "Confined", a well-known hard rock act from Fort Lauderdale, Florida. Confined was made up of Kyle Shapiro on bass and vocals, Anthony Parrinello on Guitar and Vocals, Joe Raio on Guitar, and Jason Rodman on drums.
Scars Of Life Albums (2)
What do you think about Scars Of Life?


text:
You Probably Didn’t Realize That These Celebrities Have Law Degrees
To many, the idea of Kim Kardashian pursuing a career in law is laughable. However, the reality star has devoted a lot of time to helping reform the criminal justice system. Kardashian isn’t the first celebrity to get involved in the judicial system. Check out these smartie-pants stars who have law degrees.
1. Gerard Butler
Before starring in films like 300 and P.S. I Love You, Gerard Butler spent five years studying law. The Scottish actor worked as a trainee lawyer for two years, realized it wasn’t for him, but felt obligated to keep going. Things got so bad that he made it his mission to get fired. Butler told Stephen Colbert that after missing 32 days of work in two years, he became the first Scottish lawyer trainee to be fired, a fact the actor is still proud of.
Next: A chance meeting led to a new career path.

domain: law


text:
Yikes! Sorry about that! I haven't noticed a chemical taste or any kind of aftertaste when I used it in foods. The ingredients of True Lime are (in order) Citric Acid, Maltodextrin, Lime Juice, Lime Oil, and Ascorbic Acid (Vitamin C). I would assume the lemon is the same, only with (ta da!) lemon juice and lemon oil. I just sprinkled a little True Lime in my hand and tasted it, and while it didn't taste like fresh lime, it still had lime flavor.
BTW, if I ever disappear like that again, just PM me. I just forgot I had responded to this and forgot to check it again!

domain: food


text:
Bryn Mawr Film Institute (BMFI) is a nonprofit, member-supported, motion picture theater and film education center. BMFI is dedicated to promoting shared experiences that entertain, engage, and educate audiences through a diverse range of independent-minded films, a full curriculum of courses, and an extensive program of special events. BMFI builds community through film culture, while maintaining strong connections to its historic venue's cinematic past.
Film ExhibitionBMFI shows the best in independent, international, documentary, art, and repertory films. These fine films form the nucleus around which the community development and educational programs of the Institute revolve. Over 2,000 patrons visit BMFI weekly for films, classes, and special events.
BMFI's film programming is anchored by two first-run films which are screened approximately 40 times a week. In addition, weekly programming includes between three and five repertory films or cultural presentations such as simulcast opera and theater. In 2009, there were about 100,000 admissions.
The One Night Only films and Film Series often include new and independent films presented with filmmaker discussions; repertory films are often presented with introductions by film scholars or subject matter experts. BMFI provides Going Gaga screenings for parents with babies and a Kids Matinees film series specially geared toward children. On the first Monday of every month, BMFI holds Open Screen Mondays, a chance for area filmmakers to screen their films at our theater on the big screen, free of charge.
BMFI presents filmed performances of operas from prestigious venues, including La Scala and the Salzburg Festival, as well as live simulcasts of operas from around the globe. Opera presentations include talks with staff from the Opera Company of Philadelphia. Patrons may purchase tickets for an entire series or for individual performances. BMFI also presents plays via live-delay simulcast from the National Theatre in London.
Film EducationBMFI educational programs serve approximately 800 adults per year. A robust, in-house film education department, with faculty and guest lecturers, offers seminars and courses on film history, screenwriting, film appreciation, and many other film-related topics. Throughout the year, several month-long educational courses run concurrently; on average, 15 to 20 courses per year are offered. One-day seminars and full semester courses are also offered.
Pennsylvania educators may be able to receive Act 48 credit when they attend BMFI's course, The Language of Film, thanks to our partnership with the University of the Arts.
In 2005, BMFI launched the Jacob Burns Film Center's See, Hear, Feel Film program, which brings visual literacy and critical viewing education to third-grade students in the Delaware Valley. The program has grown since its inception and now an average of 800 school children enjoy the program annually. Additionally, BMFI serves junior high, senior high, and college students through a variety of film literacy and appreciation curricula. Screenwriting and filmmaking courses are offered for various age groups.
BMFI is also home to the George Rehrauer Collection, a gift from the Haverford School, in our Film Studies Library. This collection of over 2,000 books is available for loan to Bryn Mawr Film Institute members.
Select films are followed by moderated discussions that take place in the second floor Multimedia Room. A partial list of these interactive programs includes:
- Friday afternoon discussions run by in-house faculty for particularly inspiring or provocative films currently being screened, e.g., An Inconvenient Truth and Precious
- Psychoanalytic Center of Philadelphia's character-based discussions following the screening of a newly released film one Sunday a month
- French Chats discussion group that meets in conjunction with French-language movies shown at BMFI.
BMFI also hosts Talk Cinema, a film series which offers its subscribers a unique selection of quality films independently curated by film critic Harlan Jacobson, a 30-year industry veteran. Each series previews independent and foreign films before their release. Screenings are followed by discussions led by scholars, critics, and filmmakers.
BMFI has a more varied program of feature, documentary, and alternative film offerings, than any theater in the region.
MembershipBMFI has over 6,000 members, among the largest membership of any such theater in the country. Membership is offered at several levels. Membership benefits include:
- Discounted admission to all films (free admission at Mogul level and above)
- Discounts on film education courses
- Advance ticket sales at the box office
- Invitations to free sneak previews
- Access to BMFI Film Studies library
- Program guide mailings
- Discounted admission to the Ambler Theater and the County Theater
- $1 discount on TLA movie rentals
- Discounts at area businesses and attractions

domain: artistic


Just a shady walk through the hills of a county park I hadn’t been to before.
Sanborn Skyline is off Highway 9 west of Saratoga — nestled, as we love to say in the news biz — in the woods on the east-facing side of the Santa Cruz Mountains. It goes all the way up to Skyline Boulevard and you can even hike into Castle Rock State Park if the mood strikes.
The woods are mostly pine and madrone, two of my favorite trees. Not much in the way of eye candy like roaring waterfalls or redwoods that sprouted in the time of King Arthur, but it is a nice place to get away for a few hours. While a wedding reception was happening at the park HQ, I saw practically nobody on the trails up the hillside.
One interesting artifact near the park is the American Youth Hostel, which looks like it hasn’t been doing much in the way of hosting lately.
A sign on the door said they’d only take individuals on days when there were 10 reservations or more.
Then again, the resident feline doesn’t look to have missed many meals.
Speaking of meals, there’s a couple picnic tables under the pines nearby that’d be a nice place consuming edibles in the outdoors.
I hiked up the San Andreas Trail to Skyline Boulevard and back down again. It’s the main trail through the woods till you reach the Skyline Trail. Steep in places but switch-backed pretty well. I’d rate it as moderate, difficultywise.
Pictures like this are even cooler in real life. I love the way the branches are like spokes on a wheel.
Madrone trees always have this delicate orange-brown color that a camera can’t seem to capture because of the lighting challenges. A flash overexposes it, full sun dimples it, and obscured sun doesn’t cast enough light to get the color right without a tripod and lots of shutter-speed experiments. Sometimes it’s just better to appreciate how much better the human eye is compared to mechanical gadgets.
You can’t go wrong with pictures of fallen trees, but that’ll never stop me from trying.
One of the most fascinating things about hiking in the Santa Cruz Mountains is how the ecosystem changes from one thing to another and back within minutes. This hillside at the Sunnyvale Mountain tralhead along Skyline Boulevard has grasses, scrub and tall pine all in tight proximity, depending on the available sun and moisture from the coast. An advantage to eye-candy-deficient locales is that it obliges you pay closer attention to the sounds of birds and breezes and the appearance of interesting bugs, lizards and other examples of forest flora/fauna.
For instance, there were dozens of these butterflies (moths?) fluttering around a little stream with about a half-inch of water in it. Normally a butterfly will never hang around long enough for you to take its picture — the motion of getting your camera out of its case is enough to scare one off.
This time I figured heck, they’re all thirsty for a sip from this stream, so I just sat down next to it and waiting for them to come back for a drink, which they did.
Beat-up old trail signs — can’t get enough of ’em.
Some flowers, some sky, some trees. This ain’t such a bad park, now that you mention it.
I even found a little waterfall that gave me a chance to try reducing the shutter speed to produce a more even water flow. Image stabilization in the new camera makes shots like this possible. There wasn’t enough water in the creek to get a great picture here, but it should afford some nifty opportunities during the rainy season.
One notable fact about Sanborn Skyline: it has a walk-in campground with tons of shade, but campers have to haul gear up a pretty steep slope — it was leg burner with no gear at all, must be some fun making a half-dozen trips up to a campsite from the parking lot. (Great training for backpacking, though.) It looked like maybe half the campsites were reserved, so the place was not exactly crowded. Nice place to work off your kids’ nervous energy, for sure.
It says something about the raft of outdoor opportunities available in Northern California when a park like Sanborn Skyline is strictly middle-of-the-pack. I’m not complaining. And besides, in three years of hiking and picture taking I’d never gotten a good shot of a butterfly (critics would argue this record remains intact, but hey, who listens to the critics?).


text:
1. What was West Berlin descirbed as?
- An island of capitalism in a sea of communism
- A lone standing city in dire need
- A city in desperate help to thrive
1 of 20
Other questions in this quiz
2. What is Containment?
- The combonation of the Truman Doctrine and Hoover Plan
- The combonation of the Truman Doctrine and Marshall Plan
- When America stayed isolated for as long as possible during the Cold War
3. What was the name for European countries falling one by one to communism?
- Domino effect
- Rubix effect
- Ladders effect
4. What was the Iron Curtian?
- Can't get in from north to south and vice versa
- Can't see from east to west and vice versa
- Can't see from north to south and vice versa
- Can't get in from east to west and vice versa
5. Which country liberated itself from the Germnas under Tito?

domain: history


text:
WIGAN’S Tory Police and Crime Commissioner candidate has welcomed a drop in crime across the county.
Latest figures from the independent Office for National Statistics show that over the twelve months to June recorded crime fell by ten per cent.
Former borough Mayor Michael Winstanley said today that people across Greater Manchester would be pleased to hear of the encouraging fall in recorded crime.
And it meant that there were around 13,000 fewer victims across the county.
He said: ”Greater Manchester Police can be proud of the work they have done.
“This shows that reforming our police by cutting all this red tape and getting officers onto the front line is the right approach.
“I am campaigning to be our new Police and Crime Commissioner so that I can cut crime in Greater Manchester even more and make our communities even safer.”
The first elections for the post of Police and Crime Commissioner will take place on November 15.

domain: politics


|Scott Tate, president of Tate Technology, and an E by SIPLACE pick-and-place machine.
(FL}Admittedly a lower-volume contract manufacturer, 25-year-old Tate Technology was an unlikely adopter of the market's newest mid-speed placement technology. But, its visionary leader knew that if the company was to grow, its placement capability needed an overhaul. "My job is to say 'yes'," explains Tate Technology president Scott Tate, who runs day-to-day operations at the EMS company that bears his family's name. "We have built our business on taking the jobs that nobody else wants — an approach that has served us well, providing a foot in the door for some amazing opportunities in markets as diverse as telecom, medical, industrial, and military." With production volumes as small as a single board and others in the tens of thousands, choosing a system that would offer a robust, hybrid solution and hold its own against the fast pace of technology was Tate's task.
Evaluating the Field
Armed with a binder, a complex evaluation matrix and a list of eight placement companies with which he had meetings, Tate set off to the 2016 IPC APEX expo to begin his three-day machine analysis marathon.
"When I arrived in Las Vegas, I was definitely leaning toward one particular placement system," recalls Tate, who had spent considerable time evaluating the machine at a local EMS colleague's facility. "But, the more questions I put to the vendors on my list, the more my preconceptions changed."
The word nimble describes Tate's competitive differentiator. "I've had customers walk into my office, put parts on my desk and ask how fast we could build the boards," says Tate. "In one case, we finished the job in four hours while the customer waited in our lobby. That's what sets us apart; everyone has decent people, equipment and processes, but we have the 'yes' mentality. So, our equipment has to be able to manage the work that nobody else will take on, as well as the thousand-board jobs. My decision matrix was designed on this premise."
He sought answers to an impressive array of questions: Does the machine self-calibrate? What is the human-machine interface? How is it programmed? How are parts taught? What are standard options and what are upgrades? How many feeders can the system accommodate and what is the feeder modularity? How long does it take to set up feeders? Are the JEDEC trays bolted or interchangeable? What's the machine's accuracy rating? Does it have edge conveyors, warp sensors, digital vision or laser inspection? How many nozzles on the placement head? What's the cph? What is the machine's footprint? What's the largest-sized part it can accommodate?
And that was only the start. "If you look at Tate Technology and the markets we serve, where we need to be quick and nimble, I needed a placement system that gave me the best opportunity for success in all areas," says Tate. "After countless discussions with multiple suppliers, ASM's new E by SIPLACE stood out as the optimal solution, from both a flexibility and an overall capability perspective."
Making the Difference
Tate Technology was the first E by SIPLACE Americas customer, purchasing two of the placement machines and acknowledging that there was a bit of apprehension. "We are the antithesis of the early adopter," notes Tate with a laugh. "So this was an anomaly for us, but an absolute necessity for our future. I knew we'd have a steep learning curve, though I was confident that I'd made the right decision for many reasons."
E by SIPLACE has emerged as a premier system for the mid-speed market, drawing on the proven and advanced ASM placement technology found in high-speed SIPLACE platforms and building in flexibility for the unique needs of the mid-speed sector. For Tate, the system ticked all the boxes. Every feature addresses Tate Technology's job scenario extremes, from the customer waiting in the lobby for five boards to the 5,000 board jobs, allowing Tate to effectively manage both ends of the spectrum.
|E by SIPLACE delivers advanced and economical placement capability to the mid-speed sector.
"This is the best hybrid solution," says Tate. "The feeder technology was a big factor in my decision." With 120, 8 mm (0.31 in.) feeder slots, hot-swappable feeders that simply connect and self-calibrate, and a JEDEC tray elevator that is easily removed and interchanged, E by SIPLACE delivers a high level of flexibility. That the placement system can be a short strip solution is also an important feature, and eliminates the need to spend a lot of additional time splicing or buying extra parts.
Software simplicity, the ability to teach parts, along with system networking capability, were other key considerations for Tate Technology. Using Centroid data, it is easy to panelize, cluster and optimize the job across many various lines. "ASM's E by SIPLACE has the best blending of our two types of business models — the quick-turn NPI and the high-cph, high-repeatability requirements, along with multi-machine job integration," explains Tate, adding that other systems he evaluated had no machine-to-machine network capability. "The ability to be flexible between the two production scenarios is tremendous."
Since installing the ASM pick-and-place systems, Tate Technology has realized positive, measurable results. Based on the speed and intelligence of the machines, productivity at the company has greatly improved. "The cph is exponentially higher than our older systems," says Tate. He also notes that the placement machines do not derate as much as others with gang-pick heads that claim to deliver the same cph. Tate says that a placement system that he considered was billed as a 25,000 cph machine. But, he was told he wouldn't be able to achieve actual speeds over 8,000 cph, even for simple jobs. "We have no problem getting our E by SIPLACE machines up to 14,000 cph on more complex assemblies, which is very close to the IPC-9850 rating of 14,700 cph. We have speed when we need it," says Tate.
Placement of small and complex parts is also managed easily. One job required the company to handle an oddly-configured BGA. The 1 in. (25.4 mm) square part had rows of solder balls that didn't start until about half an inch inside the perimeter. "The grid was well inside the part, so there was a massive overhang with no solder balls," explains Tate. "We tried to place these with our old system and failed miserably."
|Tate Technology’s E by SIPLACE platforms are equipped with the CP12/PP placement head, providing speed, precision and flexibility.
E by SIPLACE's digital vision system inspects 100 percent of leads and bumps — as opposed to only the part's outer edges, which is the technique employed by conventional laser systems. This technology allowed full inspection of the unique BGA and accurate placement. The system was able to place all 300 of the BGA components, solving the placement challenge. The company is now consistently placing BGAs as small as 0.74 mm (0.03 in.) square.
It is not only oddly-configured, difficult parts that make the placement machine earn its keep. "The placement precision is exceptional," says Tate. He adds that since installing the systems, quality has improved and SMT touch-up and rework have been reduced dramatically.
This all translates to a more robust bottom line. From a cost perspective, Tate estimates that the improvements to productivity have already paid dividends. A recent analysis of 14 jobs that were previously run on Tate's older machines was telling. When the identical jobs were run on the ASM machines, the data revealed a nearly 10 percent increase in efficiency, saving over 300 hours of production time. "We can produce far more product with the same staff and can now take on more technologically advanced assemblies," says Tate. "With the ability to accurately place parts as small as 01005s and as large as 45 x 98 mm (1.8 x 3.9 in.), we are well-positioned in our niche and can expand into other areas."
Though he admits it took some time for the Tate Technology team to get up to speed, Tate says that investing in the E by SIPLACE system was one of the best business decisions he's made.
"It's an impressive machine. When it's running happily, I get goosebumps. We can now take on more complex, higher-volume jobs yet still be nimble and flexible. Essentially, I get to say 'yes' to a lot more opportunities."
Contact: ASM Assembly Systems, LLC, 3975 Lakefield Court, Suite 106, Suwanee, GA 30024 770-797-3000 fax: 770-797-3457 E-mail: email@example.com Web: http://www.siplace.com


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Looking for a Latina American wife? Here are a few characteristics to look for in a potential spouse. In contrast to their bright white counterparts, Latina women benefit their stay-at-home girlfriends or wives. Women by Latin American countries in addition have a lower divorce rate than their white counterparts. Nevertheless there are certain attributes that all women will need to possess to draw a Latin American husband. Discussing look at a few of them. Weigh the advantages and drawbacks of each.
A Latin wife will position the family primary, but this does not indicate she will enable you to go out and buy yourself a highly skilled restaurant. Your girl will make you a cooked lunch. And you will expect her to will have a home-cooked meal at least once a week. In contrast, the US wife may well prefer a small household with only 1 parent, whereas a Latin woman is far more comfortable with more responsibility and less freedom.
A second quality to search for in a Latina is a sense of independence. Although you may be able to go along well using a guy who functions long hours, you should feel free to dedicate some time exclusively with your partner and enjoy your time and efforts together. It has the okay to indicate small victories, but make sure you praise her hard work and talent. She’ll most likely be coqueta and passionate.
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Irrespective of the differences in customs and language, there are many common cultural beliefs between Latinx nations. Latinx women share identical values with regards to motherhood and self-sacrifice. http://canvascorners.net/?p=47505 A better half from Latinx culture is usually expected to be a self-sacrificing member of her family. The values happen to be rooted in familismo, machismo, and marianism. The Latinx traditions is also very widely diverse.

domain: sociology


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To the Editor:
Laura Miller's review of Francine du Plessix Gray's book ''Simone Weil'' (Aug. 5) gave incomplete attention to a vital point. Since Weil was raised without religion in a family of secular Jews, and embraced Christianity in adulthood, it is no wonder that her perception was convoluted.
There is nothing arrogant, bearing on exclusivity, in the idea of Jews as a chosen people. ''Chosen'' does not signify superiority. It merely means that the ancient Hebrews were tasked with setting a good example, through deeds, for others. They were to promote justice, morality and charity, while aiding the poor. Given this scheme of things, there is no irony in the fact that they did not seek to convert their neighbors to Judaism. If Weil had been broader in her understanding and more willing to learn, she might not have adopted an erroneous conclusion.
Elliott A. Cohen
Santa Barbara, Calif.Continue reading the main story

domain: literature


South Korea’s Ministry of Science and ICT, and the National Election Commission (NEC), have announced plans for setting up a voting system powered by blockchain.
If results are successful, the system will be considered for online elections, according to the NEC.
Although online voting has been utilized in the country—the first time in 2013—use among citizens has been limited, to about 5.64 million people in all due to security concerns. The country has a little over 50 million people, of which 42.5 million are registered voters, with an average turnout of 64.3%.
ZDNet said that the government expected blockchain to aid with voter authentication and result saving, where the added transparency and security would allay fears of fraud and hacking. The results of elections, where votes are to be inputted by mobile devices and personal computers, will be viewable as the data is included in the blockchain.
The initial trials will begin in December, with surveys conducted by Seoul National University’s Blockchain Society and the Korea Internet & Security Agency. The NEC said that aside from blockchain, it was also looking at applying artificial intelligence (AI), big data, and Internet of Things (IoT) to the voting system.
The use of blockchain for polling in South Korea is not altogether new. Last year, the province of Gyeonggi-do used Blocko’s Coinstack platform to decide on the approval of 527 community projects. This involved the votes of 9,000 residents.
In Japan, the city of Tsukuba has made use of blockchain for choices on local “social contribution programs.” Although there were reports of some difficulties for some voters, the test was declared a success.
Zug, the ‘Crypto Valley’ of Switzerland, has conducted municipal voting via blockchain, though this involved only 72 citizens. The city government intends to expand the use of blockchain, to be part of its digital ID system.
In the U.S., there have been several initiatives involving distributed ledger technology for voting. In West Virginia, its first use has been limited to allowing overseas members of the military to vote, with a mobile app. In Maine, proposals have been considered for use of blockchain in municipal elections.
New to blockchain? Check out CoinGeek’s Blockchain for Beginners section, the ultimate resource guide to learn more about blockchain technology.


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- Creating a
The Progulator Team is excited to take you through the nooks and crannies of Terminal Twilight, the newest effort by White Willow, so be prepared for the cluster bomb that is four individuals collaborating on an album review. We are quite pleased that we were deemed “worthy” to receive our first promotional copy of an album from the Norwegian prog masters, and that Jacob let Markus bounce his silly questions off of him as well. To celebrate, we all wanted to pitch in our two cents, and really dig into this meaty morsel of music. So, without further blathering, here we go:
A Brief, Yet Informative Pontification of White Willow’s History by Markus “The Padre” Cueva
For any of you who have read my humble works on this site, you probably know by now the fetish that I have for Scandinavian progressive music. Does this make me an unbiased reviewer? Absolutely not, which is why my fellow compatriots are doing all the dirty work. I will, however, start by saying that this album has proven to be nothing short of another stellar release from White Willow (to find out why… just keep reading).
White Willow has been around for more than 15 years, which in music years is long enough to have a back catalog but not long enough to be considered too old to be seen on stage anymore (I’m looking at you, Mick Jagger). I’ve already covered their place in the rebirth of progressive music in the 90’s (which you can read here, ’cause I’m not repeating myself), and I’m starting to think that this rebirth has less to do with the bands themselves (except for the entity known as Änglagård, and I don’t think I have to explain myself) and more to do with a talented and diverse pool of musicians that just happen to walk this earth at around the same time. What are the chances?
The lineup for Terminal Twilight makes my point for me. This current incarnation White Willow features the drummer for Änglagård, the keyboard wizard and leader of Wobbler, the flautist from Jaga Jazzist, and even a guest appearance from Steven Wilson’s partner in the band No-Man. Those of you unfamiliar with the bands I just named have some Googling to do – after you’ve finished this review, of course. I know there seems to be an almost incestuous relationship with bands and musicians in the Scandinavian prog scene, with musicians being associated with multiple groups (ahem… Mattias Olsson), but that’s still an impressively talented group of individuals that guitarist and band leader Jacob Holm-Lupo has assembled.
And that talented group of individuals, through the magic of pure human creativity and some nifty home recording techniques, have delivered a well-produced and immaculately composed album. And I liked it. But since Tyson received the promo copy INSTEAD of me, I wasn’t able to have as much special alone time with the album as he did. So I’ll let HIM tell you about it.
Tyson’s Nonsensical, ADD thoughts
Terminal Twilight arrived at my doorstep the same day that Opeth’s new album Heritage came in, the week after Dream Theater’s new album, a week before Steven Wilson’s Grace for Drowning, the same time I was trying to get my Dungeons and Dragons group back together, and while trying to finish Fallout 3 before all the awesome new games come out. Now, Opeth is in my top 5 artists right now, and I pretty much instantly love anything that Steven Wilson touches (and he touched Heritage quite a bit, incidentally), so to say that Terminal Twilight had some stiff competition for my limited attention span would probably be an understatement. Add that to the fact that Dream Theater’s new album was extremely fascinating due to the new dynamic present with the departure of Mike Portnoy, and it being one of the most inconsistently mixed albums I’ve heard in a while, my ears were in for a busy and very fulfilling month of amazing music.
Terminal Twilight by far got the most attention. Initially, it was because I had a review to write, and a deadline to meet. But, as I started spinning the other records, I was constantly drawn back to Terminal Twilight, and it even managed to pull me away from the ps3 more than once. There was something in this album that really spoke to me, something very personal and genuine, that Opeth and Dream Theater didn’t give me; while interesting and very good, they felt aloof. Terminal Twilight feels painstakingly crafted with a lot of emotion and care. The keyboard sounds and layers are intricately woven together, and the composition meticulously forged such that each song builds to a climax in a way that is both breathtaking and beautiful. Mattias’ drums are raw and biting, his sounds and samples are fitting and add depth and contrast, Lars’ sounds and layering are beautiful, Ketil’s flute playing is amazing, and Sylvia’s vocals are just perfectly, beautifully ethereal, either haunting, or relaxing depending on the song. There is also a subtle post-rock vibe that I really like, in the drumming and guitar, that helps build each song, for me at least. This album took me a little by surprise, but in a very good way.
The first thing I noticed was how good the album sounded. Terminal Twilight is easily one of the better sounding albums I’ve ever heard, especially compared to any music that’s been recently released. It doesn’t have the slickness of an expensive studio, but there’s just something so pure and natural about it that really complimented the personal and intimate nature of the music. To my surprise, Jacob mentioned in our interview that he recorded everything himself, onto his laptop no less (I’m sure its a nice laptop, but still). His goal, instead of doing a lot of post production, was to play with mic placement, mic choice, and room tone, letting the character of the really awesome vintage synths and other instruments speak for themselves, and they did so in a glorious way. Even though he was unsure at first, it worked amazingly well. For those of you who watched/listened to that video that they put up on youtube, it is in my opinion a very good preview of the album. So, with my general album impressions out of the way, I want to dig in to a few of my favorite tracks.
Hawks Circle the Mountain
This song fits easily into my top 3 for this album. It opens with some really dark keyboards and brutal chords (hello mellotron, I love you), followed shortly by Sylvia’s ethereal voice singing a nice melodic contrast to the synths, then it just gets better from there, going into some really interesting instrumental sections. The bass tone on this song is really aggressive which is just an interesting counter to the more legato and melodic instruments, but my favorite thing is the way that they build in and vary the initial motifs throughout the song to create a very impressive climax by adding subtle layers. The drums sound raw and biting at times, while mellow and beautiful at others. The electronic drum sounds are also interesting, and give good texture. Very solid track, so plan on multiple listens.
Ah, Tim Bowness, how great your voice sounds. I don’t think anyone else could have done this track justice. I don’t have much to say about this track, just because I can’t quite put my finger on why I like it so much. The subtle variance and building is there for sure, but I think its just the melancholy mood of the guitar, and sad nostalgia of the lyrics that talk of opportunities and dreams past that didn’t come to fruition that really strikes a chord with me. It puts me in that introspective mood that I fall into so often, then wraps around me like a warm blanket in winter.
This is another top 3 for me, possibly edging out the other 2, but I can’t quite decide. The intro is beautiful and manages to not sound contrived, I think due to the flute/synth. Even though the chord progression is very mainstream and predictable (which isn’t necessarily a bad thing), it manages to rise above sounding mainstream and predictable, resulting in a very beautiful first section that builds quite strongly into the strange instrumental section. The first part of this song showcases the subtle building composition that I love as good as any part on this album, with Lars and Jacob adding layers very delicately to the melody until it builds into a huge wall of sound. The picture painted for me is like a cozy post-apocalyptic evening, or (probably closer to the truth), a cozy evening/winter spent in an abandoned run down building watching while the world is falling apart. The lyrics definitely hint at something like that, and I’ve been playing a LOT of fallout 3 lately, so that may be to blame. The middle instrumental section is unsettling, in a good way, giving a sense of chaos and destruction, only to be book-ended by a reprise of the beautiful intro, detailing more destruction watched in peace from far above. The end section builds in tension until Sylvia takes us into oblivion with her haunting voice echoing alone. Again, I really found an emotional hook in this song, since there a huge and very important chunk of my life that is falling apart before my eyes, and I’ve had to step away from it all, and just marvel, watching from as much a distance as I can in a cozy shelter with my wife. “and the winds that howl and howl, like a lost and lonely beast, while this empty high-rise shivers, but for floor 67 where you and I sleep…” Go watch this before you listen.
Here’s my other top 3 song. This song is dark and epic, with some very emotional moments. There is a lot of pain and turmoil present in the sound, which, from what I can hear of the lyrics, makes sense. I don’t have a lot to say about this song because I keep getting distracted listening to it. I just really like it. The same building, layering, and very nice drum sounds are present here too. A very beautiful and moving song.
A Second (and Third) Opinion
First off, my biggest reaction definitely came from the song Kansas Regrets. I had been thoroughly enjoying the album all along, but when this song came on, I about pissed my pants in excitement and surprise: IS THAT TIM BOWNESS!!? A few seconds of Googling (since the only thing I knew about the album beforehand was that I would probably like it) to confirm that it was indeed Tim’s excellent and seductive (I use that term in the straightest way possible) voice featured on the song. You might be familiar with Tim Bowness from his collaboration with Steven Wilson on the project No-Man (if you haven’t, go buy Flowermouth).The soothing atmosphere of the song suited Tim’s voice perfectly, and I especially enjoyed the gentle swelling of keyboards during the chorus. This song was so relaxing I felt like I was getting the benefits of a nice long nap, in spite of being fully awake.
I don’t want to let my love of Tim distract from the vocal work of Sylvia Erichsen, however. Her vocals are beautiful and almost ethereal, being either soothing or haunting depending on the context of the song. A vocalist can be technically good, but not good for the music, but she fits the music perfectly. It feels like it was written just for her (and apparently it was, according to Markus’s interview). The vocals grabbed my attention from the album-opener Hawks Circle the Mountain, and impressed me all throughout the album.
Overall, the album is very ambient and atmospheric, with plenty of lush depth and texture provided by the excellent keys, including plenty of mellotron, which I absolutely love (my wife jests that a musician just needs to add mellotron to their music, and I will like them no matter what their music is like otherwise. This might be true. Perhaps I’ll try starting a mellotron punk band). Ostentatious displays of viruosity are thankfully absent, as I feel they would mar the carefully crafted atmosphere. Which isn’t to say that the music is simplistic, because it isn’t. Technical skill is everywhere apparent, but not thrown in the listener’s face (or perhaps shoved down their ear might be a better phrase).
Matt “The Italian” DiGiordano
Waiting to write a review until the moment where you get put in charge of reading and doing light editing of other reviews (which are fantastic) is the kind of situation where you realize that you’re at a loss for words, except for…DITTO! I’ll probably just end up echoing a lot of what’s been said, so I’ll keep it brief and simple. By the way, “Hawks Circle the Mountain” is worth the price of the album all by itself. Just saying. It’s that good. Grim and haunting mellotron and synths, infectious grooves, gorgeous vocals, pure bliss.
Honestly, Terminal Twilight is an album that does just about everything right. The first thing that caught my attention and which continues to blow my mind listen after listen is the production. This record just sounds so natural. It’s not only crystal clear, but incredibly rich; I’m like sitting around here looking over my shoulder every five seconds and wondering whether Lars’ massive piles of analog gear are going to collapse on my head from all around me. Any fan of analog synths will surely soil their pants at the incredible display of sound and texture. They sound that good. Somehow every sparkle is there without anything getting squashed in production. Once again, it has all the tangible awesomeness that you want without the poor recording quality that you get on many records, both old and new. It would be unfair, however, to say that it’s only the synths that sound great. In reality, every single instrument on this album cuts through the mix in splendid ways that just leave you grinning throughout.
What can I say about the composition? Like the production, it’s natural and has great flow. Sections of songs never ever feel forced. Everything that happens feels like it’s supposed to happen; there’s never a random moment where you feel like a decision was based off of a situation where the band had an agenda of what had to be there. I really feel like the songs move in the direction that they want to go rather than where someone wanted to pull them, which I think shows a ton of maturity from the band.
White Willow managed to make every track a feast of texture and ambiance with memorable vocals and melodies. In short, for me, this album simply sounds good and feels good. There is a very strong ethereal quality which is present throughout the album that makes the compositions very three dimensional. You can’t just turn this record on soft and expect to feel all the great stuff that the band is doing; you actually need the sound waves to hit you and wash over you. Since no one else has made the sales pitch yet, I will. Go out and buy this record, turn it up, and swim in a fantastic pool of sonic pleasure.

domain: entertainment


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Pedestrian Killed in Crash at West El Camino Avenue and Northgate Boulevard
Victim Hit by Vehicle in Fatal Sacramento Accident
Sacramento, CA (January 1, 2020) – A pedestrian was killed in a crash in Sacramento. The fatal accident occurred on the evening of January 1 at West El Camino Avenue and Northgate Boulevard.
A man was hit by a vehicle at the intersection. He died at the accident scene.
Our heartfelt condolences go out to the friends and loved ones of the victim.

domain: news


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A standoff with an armed man inside a Lancaster City home has ended and the suspect is in police custody. The man was taken away in handcuffs just before 9 a.m. after engaging in a standoff with police along the 600 block of South Queen Street.
Authorities were called to the home around 3:30 a.m. for a report of shots fired. When officers arrived at the scene the suspect fired additional shots before barricading himself inside a home with a woman and children, according to the Lancaster County District Attorney Craig Stedman.
The Lancaster County Special Emergency Response Team (SERT) was called in to assist Lancaster City police and nearby residents were evacuated, Stedman said.
No injuries have been reported.
Police have not released the identity of the suspect.