Madrassa Education in Pakistan: Assisting the Taliban’s Resurgence

The education received in madrassas located in Pakistan is contributing to the Taliban’s resurgence in Afghanistan

Nest Success and Duckling Survival of Greater Scaup, Aythya marila, at Grassy Island, New Brunswick

Nesting biology and duckling survival of Greater Scaup (Aythya marila) at Grassy Island on the Saint John River in southern New Brunswick were compared between 1995 and 1996. Grassy Island in New Brunswick is an area that is notably removed from other scaup breeding areas, being located farther south from main breeding areas in North America. The Mayfield estimates of nest success were 61% and 21% in 1995 and 1996, respectively. Mean daily survival rates were 0.99 in 1995 and 0.96 in 1996 and were significantly different (t = 4.86, P < 0.001). Duckling survival was estimated to range from 38 to 54% in 1995, and was 8% in 1996. The lower breeding success in 1996 may have been due to factors associated with decreased temperatures and increased precipitation, but the fact that the breeding location is atypical to other Greater Scaup breeding areas should not be overlooked

Accurate Masses for the Primary and Secondary in the Eclipsing White Dwarf Binary NLTT 11748

We measure the radial velocity curve of the eclipsing detached white dwarf binary NLTT 11748. The primary exhibits velocity variations with a semi-amplitude of 273 km s⁻¹ and an orbital period of 5.641 hr. We do not detect any spectral features from the secondary star or any spectral changes during the secondary eclipse. We use our composite spectrum to constrain the temperature and surface gravity of the primary to be T_eff = 8690 ± 140 K and log g = 6.54 ± 0.05, which correspond to a mass of 0.18 M ☉. For an inclination angle of 89.°9 derived from the eclipse modeling, the mass function requires a 0.76 M ☉ companion. The merger time for the system is 7.2 Gyr. However, due to the extreme mass ratio of 0.24, the binary will most likely create an AM CVn system instead of a merger

INTEGRATE: Gene fusion discovery using whole genome and transcriptome data

While next-generation sequencing (NGS) has become the primary technology for discovering gene fusions, we are still faced with the challenge of ensuring that causative mutations are not missed while minimizing false positives. Currently, there are many computational tools that predict structural variations (SV) and gene fusions using whole genome (WGS) and transcriptome sequencing (RNA-seq) data separately. However, as both WGS and RNA-seq have their limitations when used independently, we hypothesize that the orthogonal validation from integrating both data could generate a sensitive and specific approach for detecting high-confidence gene fusion predictions. Fortunately, decreasing NGS costs have resulted in a growing quantity of patients with both data available. Therefore, we developed a gene fusion discovery tool, INTEGRATE, that leverages both RNA-seq and WGS data to reconstruct gene fusion junctions and genomic breakpoints by split-read mapping. To evaluate INTEGRATE, we compared it with eight additional gene fusion discovery tools using the well-characterized breast cell line HCC1395 and peripheral blood lymphocytes derived from the same patient (HCC1395BL). The predictions subsequently underwent a targeted validation leading to the discovery of 131 novel fusions in addition to the seven previously reported fusions. Overall, INTEGRATE only missed six out of the 138 validated fusions and had the highest accuracy of the nine tools evaluated. Additionally, we applied INTEGRATE to 62 breast cancer patients from The Cancer Genome Atlas (TCGA) and found multiple recurrent gene fusions including a subset involving estrogen receptor. Taken together, INTEGRATE is a highly sensitive and accurate tool that is freely available for academic use

Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study

Objective: To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications. Design: Prospective, propensity score matched cohort study. Setting: General teaching hospital in Boston, Massachusetts, United States, 2006-10. Participants: 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. Main outcome measures: The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation 3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. Results: The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation to values less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). Conclusion: The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited

Ultracontinuous single haplotype genome assemblies for the domestic cat (Felis catus) and Asian leopard cat (Prionailurus bengalensis)

In addition to including one of the most popular companion animals, species from the cat family Felidae serve as a powerful system for genetic analysis of inherited and infectious disease, as well as for the study of phenotypic evolution and speciation. Previous diploid-based genome assemblies for the domestic cat have served as the primary reference for genomic studies within the cat family. However, these versions suffered from poor resolution of complex and highly repetitive regions, with substantial amounts of unplaced sequence that is polymorphic or copy number variable. We sequenced the genome of a female F1 Bengal hybrid cat, the offspring of a domestic cat (Felis catus) x Asian leopard cat (Prionailurus bengalensis) cross, with PacBio long sequence reads and used Illumina sequence reads from the parents to phase \u3e99.9% of the reads into the two species’ haplotypes. De novo assembly of the phased reads produced highly continuous haploid genome assemblies for the domestic cat and Asian leopard cat, with contig N50 statistics exceeding 83 Mb for both genomes. Whole genome alignments reveal the Felis and Prionailurus genomes are colinear, and the cytogenetic differences between the homologous F1 and E4 chromosomes represent a case of centromere repositioning in the absence of a chromosomal inversion. Both assemblies offer significant improvements over the previous domestic cat reference genome, with a 100% increase in contiguity and the capture of the vast majority of chromosome arms in one or two large contigs. We further demonstrated that comparably accurate F1 haplotype phasing can be achieved with members of the same species when one or both parents of the trio are not available. These novel genome resources will empower studies of feline precision medicine, adaptation and speciation

Host-like carbohydrates promote bloodstream survival of Vibrio vulnificus in vivo

Sialic acids are found on all vertebrate cell surfaces and are part of a larger class of molecules known as nonulosonic acids. Many bacterial pathogens synthesize related nine-carbon backbone sugars; however, the role(s) of these non-sialic acid molecules in host-pathogen interactions is poorly understood. Vibrio vulnificus is the leading cause of seafood-related death in the United States due to its ability to quickly access the host bloodstream, which it can accomplish through gastrointestinal or wound infection. However, little is known about how this organism persists systemically. Here we demonstrate that sialic acid-like molecules are present on the lipopolysaccharide of V. vulnificus, are required for full motility and biofilm formation, and also contribute to the organism's natural resistance to polymyxin B. Further experiments in a murine model of intravenous V. vulnificus infection demonstrated that expression of nonulosonic acids had a striking benefit for bacterial survival during bloodstream infection and dissemination to other tissues in vivo. In fact, levels of bacterial persistence in the blood corresponded to the overall levels of these molecules expressed by V. vulnificus isolates. Taken together, these results suggest that molecules similar to sialic acids evolved to facilitate the aquatic lifestyle of V. vulnificus but that their emergence also resulted in a gain of function with life-threatening potential in the human host

Safety and Efficacy of 5 Years of Treatment With Recombinant Human Parathyroid Hormone in Adults With Hypoparathyroidism

CONTEXT: Conventional hypoparathyroidism treatment with oral calcium and active vitamin D is aimed at correcting hypocalcemia but does not address other physiologic defects caused by PTH deficiency. OBJECTIVE: To evaluate long-term safety and tolerability of recombinant human PTH (1-84) [rhPTH(1-84)]. DESIGN: Open-label extension study; 5-year interim analysis. SETTING: 12 US centers. PATIENTS: Adults (N = 49) with chronic hypoparathyroidism. INTERVENTION(S): rhPTH(1-84) 25 or 50 µg/d initially, with 25-µg adjustments permitted to a 100 µg/d maximum. MAIN OUTCOME MEASURE(S): Safety parameters; composite efficacy outcome was the proportion of patients with ≥50% reduction in oral calcium (or ≤500 mg/d) and calcitriol (or ≤0.25 µg/d) doses, and albumin-corrected serum calcium normalized or maintained compared with baseline, not exceeding upper limit of normal. RESULTS: Forty patients completed 60 months of treatment. Mean albumin-corrected serum calcium levels remained between 8.2 and 8.7 mg/dL. Between baseline and month 60, levels ± SD of urinary calcium, serum phosphorus, and calcium-phosphorus product decreased by 101.2 ± 236.24 mg/24 hours, 1.0 ± 0.78 mg/dL, and 8.5 ± 8.29 mg2/dL2, respectively. Serum creatinine level and estimated glomerular filtration rate were unchanged. Treatment-emergent adverse events (AEs) were reported in 48 patients (98.0%; hypocalcemia, 36.7%; muscle spasms, 32.7%; paresthesia, 30.6%; sinusitis, 30.6%; nausea, 30.6%) and serious AEs in 13 (26.5%). At month 60, 28 patients (70.0%) achieved the composite efficacy outcome. Bone turnover markers increased, peaked at ∼12 months, and then declined to values that remained above baseline. CONCLUSION: Treatment with rhPTH(1-84) for 5 years demonstrated a safety profile consistent with previous studies and improved key biochemical parameters

Differences in small intestinal apparent amino acid digestibility of raw bovine, caprine, and ovine milk are explained by gastric amino acid retention in piglets as an infant model

BackgroundThe rate of stomach emptying of milk from different ruminant species differs, suggesting that the small intestinal digestibility of nutrients could also differ across these milk types.ObjectiveTo determine the small intestinal amino acid (AA) digestibility of raw bovine, caprine, and ovine milk in the piglet as an animal model for the infant.MethodsSeven-day-old piglets (n = 12) consumed either bovine, caprine, or ovine milk diets for 15 days (n = 4 piglets/milk). On day 15, fasted piglets received a single meal of fresh raw milk normalized for protein content and containing the indigestible marker titanium dioxide. Entire gastrointestinal tract contents were collected at 210 min postprandially. Apparent AA digestibility (disappearance) in different regions of the small intestine was determined.ResultsOn average, 35% of the dietary AAs were apparently taken up in the small intestine during the first 210 min post-feeding, with 67% of the AA digestibility occurring in the first quarter (p ≤ 0.05) and 33% in the subsequent two quarters. Overall, except for isoleucine, valine, phenylalanine, and tyrosine, the small intestinal apparent digestibility of all AAs at 210 min postprandially in piglets fed ovine milk was, on average, 29% higher (p ≤ 0.05) than for those fed bovine milk. Except for lysine, there was no difference in the apparent digestibility (p > 0.05) of any AAs between piglets fed caprine milk or ovine milk. The apparent digestibility of alanine was higher (p ≤ 0.05) in piglets fed caprine milk than those fed bovine milk. When apparent digestibility was corrected for gastric AA retention, only small differences in the small intestinal apparent digestibility of AAs were observed across milk types.ConclusionBovine, caprine and ovine milk had different apparent small intestinal AA digestibility at 210 min postprandially. When corrected for gastric AA retention, the differences in apparent digestibility across species largely disappeared. The apparent AA digestibility differed across small intestinal locations