The tibiofibular syndesmosis. Evaluation of the ligamentous structures, methods of fixation, and radiographic assessment.
Twenty-five fresh-frozen cadaveric specimens were used to evaluate the role of the syndesmotic ligaments when the ankle is loaded with external rotation torque. An apparatus was constructed that allowed pure external-rotation torque to be applied through the ankle with the foot in neutral flexion. The apparatus provided solid fixation of the tibia while allowing free movement of the fibula in all planes. The syndesmotic ligaments were incrementally sectioned, and direct measurements of anatomical diastasis were made. Mortise and lateral radiographs were made at each increment under both loaded (5.0 newton-meters) and unloaded conditions. After all structures of the syndesmosis had been divided, the syndesmosis was reduced and was repaired with one or two screws. The strength of the repair was measured with incremental increases in torque of 1.0 newton-meter. The radiographs were measured by three independent observers in a blind fashion. In order to evaluate intraobserver error, each observer was randomly given forty radiographs to reinterpret. Diastasis and rotation were found to be related to the amount of injury of the ligament (p < 0.0001). After the entire syndesmosis had been divided, application of a 5.0-newton-meter torque resulted in a mean diastasis of 7.3 millimeters. The subsequent repair of the anterior tibiofibular ligament with suture failed at a mean of 2.0 newton-meters (range, 1.0 to 6.0 newton-meters) of torque. Repair with two screws was found to be stronger than repair with one, with the first construct failing at a mean of 11.0 newton-meters (range, 5.0 to 15.0 newton-meters) and the second, at a mean of 6.2 newton-meters (range, 2.0 to 10.0 newton-meters) (p = 0.0005). Failure of the screw fixation was not associated with the maximum previous diastasis (p = 0.13). Measurements of anatomical diastasis were compared with measurements made on the mortise and lateral radiographs. Measurements on the stress mortise radiographs had a weak correlation with diastasis (r = 0.41, p < 0.0001). However, measurements on the stress lateral radiographs had a higher correlation (r = 0.81, p < 0.0001). Additionally, interobserver correlation was significantly higher for the measurements on the lateral radiographs (r = 0.87, p < 0.0001) than for those on the mortise radiographs (r = 0.56, p < 0.0001). Intraobserver correlation for the three observers was poor with regard to the measurements on the mortise radiographs (r = 0.12, 0.42, and 0.25). The respective correlations for the measurements on the lateral radiographs were r = 0.81, 0.90, and 0.89.(ABSTRACT TRUNCATED AT 400 WORDS)


Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable stage I-II non-small-cell lung cancer.
Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations. A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified for target dose heterogeneity and the dose to normal tissue/structures. The protocol required each site to plan the patient's treatment using unit density, and another plan with the same monitor units and applying density corrections was also submitted. These plans were compared to determine the dose differences. Two-sided, paired Student's t tests were used to evaluate these differences. With heterogeneity corrections applied, the planning target volume receiving >/=60 Gy decreased, on average, 10.1% (standard error, 2.7%) from 95% (p = .001). The maximal dose to any point >/=2 cm away from the planning target volume increased from 35.2 Gy (standard error, 1.7) to 38.5 Gy (standard error, 2.2). Statistically significant dose differences were found with the heterogeneity corrections. The information provided in the present study is being used to design future heterogeneity-corrected RTOG stereotactic body radiotherapy lung protocols to match the true dose delivered for RTOG 0236.


Expression of parathyroid hormone-related peptide (PTH-rp) and its receptorin the porcine ovary: regulation by transforming growth factor-beta and possible paracrine effects of granulosa cell PTH-rp secretion on theca cells.
Parathyroid hormone-related peptide (PTH-rp) and the PTH-rp receptor are expressed in certain cancers as well as in many normal tissues. To evaluate the expression of this Ca(2+)-regulating hormone and its receptor in porcine ovary, we isolated partial cDNAs encoding homologous PTH-rp and PTH-rp receptor using reverse transcription-polymerase chain reaction (RT-PCR). The cDNA encoding PTH-rp (419 base pairs [bp]) was 92% and 87% homologous to human and rat sequences, respectively, while the PTH-rp receptor clone (167 bp) was 94% and 91% identical to the human and rat genes. Qualitative estimates of PTH-rp mRNA by RT-PCR indicated that the PTH-rp gene is expressed at high levels in the corpus luteum but is undetectable in granulosa and theca cells isolated from small (1-5 mm) and medium-sized (5-8 mm) antral follicles. In contrast, PTH-rp receptor transcripts were most abundant in corpora lutea and theca cells, and least abundant (albeit detectable) in granulosa cells. Regulation of PTH-rp protein production was assessed in serum-free monolayer cultures of porcine granulosa cells. Transforming growth factor (TGF)-beta1 (100 ng/ml) increased PTH-rp concentrations (assayed by two-site immunoradiometric assay of culture media) as well as corresponding PTH-rp mRNA accumulation (assessed by RT-PCR) in a time-dependent manner, with maximal responses of 3- to 5-fold at 96 h. TGF-beta1 dose-response studies revealed an ED(50) of 0. 24-0.38 ng/ml with a maximal effect at 30 ng/ml. Other growth factors and hormones, including insulin, insulin-like growth factor (type I), epidermal growth factor, FSH, estradiol, and interleukin-1, failed to alter PTH-rp secretion. Biological effects of PTH-rp were evident in purified porcine theca cells. Using the Ca(2+)-sensitive fluorescent indicator dye, fura-2, and digital imaging videomicroscopy, we found that PTH-rp (1 microM) stimulated intracellular free calcium ion concentrations ([Ca(2+)](i)) in single porcine theca cells. The [Ca(2+)](i) elevation was characterized by a slow and prolonged rise. After PTH-rp stimulation, theca cells maintained responsiveness to hormone stimulation by LH, which elicited a typical theca cell [Ca(2+)](i) response. Our results allow a hypothesis of a paracrine intrafollicular signaling system involving interaction between theca cell-derived TGF-beta and granulosa cell-derived PTH-rp, with feedback by PTH-rp on theca cells. Alternatively, expression of mRNAs encoding PTH-rp and its receptor in corpora lutea suggests that this peptide may play a role in luteal cell function. The precise role of this intraovarian PTH-rp system will require further study.


Dynorphins other than dynorphin A(1-17) lack spinal antianalgesic activity but do act on dynorphin A(1-17) receptors.
In recent publications we have proposed that dynorphin (Dyn) A(1-17) functions as an antianalgesic modulator to oppose opioid-induced antinociception in mice. In the present experiments using the tail-flick response in mice, other Dyns [Dyn A(1-8), Dyn A(1-13), Dyn A(2-17), Dyn B and alpha- and beta-neoendorphin] when administered intrathecally (i.t.) were shown not to have antianalgesic activity even at high doses (0.5-1 pmol). These Dyns, i.t., did not antagonize the antinociception produced by physostigmine administered i.c.v. or morphine given i.t. These Dyns lacked the intrinsic antianalgesic activity of Dyn A(1-17). However, they had affinity for Dyn A(1-17) receptors as shown in several ways. 1) The antagonism of physostigmine antinociception produced by Dyn A(1-17) given i.t. was reversed by these Dyns given together with Dyn A(1-17). 2) The effect of endogenously released Dyn A(1-17) was reversed. Administered i.c.v., clonidine simultaneously activates antinociceptive and antianalgesic systems [latter mediated spinally by Dyn A(1-17) release]. Thus, these Dyns given i.t. inhibited the action of endogenously released Dyn A(1-17) and allowed the full manifestation of the antinociceptive action of clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)


Cholinergic stimulation enhances Bayesian belief updating in the deployment of spatial attention.
The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision.


Convolutional Oriented Boundaries: From Image Segmentation to High-Level Tasks.
We present Convolutional Oriented Boundaries (COB), which produces multiscale oriented contours and region hierarchies starting from generic image classification Convolutional Neural Networks (CNNs). COB is computationally efficient, because it requires a single CNN forward pass for multi-scale contour detection and it uses a novel sparse boundary representation for hierarchical segmentation; it gives a significant leap in performance over the state-of-the-art, and it generalizes very well to unseen categories and datasets. Particularly, we show that learning to estimate not only contour strength but also orientation provides more accurate results. We perform extensive experiments for low-level applications on BSDS, PASCAL Context, PASCAL Segmentation, and NYUD to evaluate boundary detection performance, showing that COB provides state-of-the-art contours and region hierarchies in all datasets. We also evaluate COB on high-level tasks when coupled with multiple pipelines for object proposals, semantic contours, semantic segmentation, and object detection on MS-COCO, SBD, and PASCAL; showing that COB also improves the results for all tasks.


Early enteral nutrition support in patients undergoing liver transplantation.
The purpose of this study was to determine the effects of early postoperative tube feeding on outcomes of liver transplant recipients. Fifty transplant patients were randomized prospectively to receive enteral formula via nasointestinal feeding tubes (tube-feeding [TF] group) or maintenance i.v. fluid until oral diets were initiated (control group). Thirty-one patients completed the study. Resting energy expenditure, nitrogen balance, and grip strength were measured on days 2, 4, 7, and 12 after liver transplantation. Calorie and protein intakes were calculated for 12 days posttransplant. Tube feeding was tolerated in the TF group (n = 14). The TF patients had greater cumulative 12-day nutrient intakes (22,464 +/- 3554 kcal, 927 +/- 122 g protein) than did the control patients (15,474 +/- 5265 kcal, 637 +/- 248 g protein) (p < .002). Nitrogen balance was better in the TF group on posttransplant day 4 than in the control group (p < .03). There was a rise in the overall mean resting energy expenditure in the first two posttransplant weeks from 1487 +/- 338 to 1990 +/- 367 kcal (p = .0002). Viral infections occurred in 17.7% of control patients compared with 0% of TF patients (p = .05). Although other infections tended to occur more frequently in the control group vs the TF group (bacterial, 29.4% vs 14.3%; overall infections, 47.1% vs 21.4%), these differences were not statistically significant. Early posttransplant tube feeding did not influence hospitalization costs, hours on the ventilator, lengths of stay in the intensive care unit and hospital, rehospitalizations, or rejection during the first 21 posttransplant days. Early posttransplant tube feeding was tolerated and promoted improvements in some outcomes and should be considered for all liver transplant patients.


Comprehensive identification of the full-length transcripts and alternative splicing related to the secondary metabolism pathways in the tea plant (Camellia sinensis).
Flavonoids, theanine and caffeine are the main secondary metabolites of the tea plant (Camellia sinensis), which account for the tea's unique flavor quality and health benefits. The biosynthesis pathways of these metabolites have been extensively studied at the transcriptional level, but the regulatory mechanisms are still unclear. In this study, to explore the transcriptome diversity and complexity of tea plant, PacBio Iso-Seq and RNA-seq analysis were combined to obtain full-length transcripts and to profile the changes in gene expression during the leaf development. A total of 1,388,066 reads of insert (ROI) were generated with an average length of 1,762 bp, and more than 54% (755,716) of the ROIs were full-length non-chimeric (FLNC) reads. The Benchmarking Universal Single-Copy Orthologue (BUSCO) completeness was 92.7%. A total of 93,883 non-redundant transcripts were obtained, and 87,395 (93.1%) were new alternatively spliced isoforms. Meanwhile, 7,650 differential expression transcripts (DETs) were identified. A total of 28,980 alternative splicing (AS) events were predicted, including 1,297 differential AS (DAS) events. The transcript isoforms of the key genes involved in the flavonoid, theanine and caffeine biosynthesis pathways were characterized. Additionally, 5,777 fusion transcripts and 9,052 long non-coding RNAs (lncRNAs) were also predicted. Our results revealed that AS potentially plays a crucial role in the regulation of the secondary metabolism of the tea plant. These findings enhanced our understanding of the complexity of the secondary metabolic regulation of tea plants and provided a basis for the subsequent exploration of the regulatory mechanisms of flavonoid, theanine and caffeine biosynthesis in tea plants.


Polymerase ε1 mutation in a human syndrome with facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome").
DNA polymerase ε (Polε) is a large, four-subunit polymerase that is conserved throughout the eukaryotes. Its primary function is to synthesize DNA at the leading strand during replication. It is also involved in a wide variety of fundamental cellular processes, including cell cycle progression and DNA repair/recombination. Here, we report that a homozygous single base pair substitution in POLE1 (polymerase ε 1), encoding the catalytic subunit of Polε, caused facial dysmorphism, immunodeficiency, livedo, and short stature ("FILS syndrome") in a large, consanguineous family. The mutation resulted in alternative splicing in the conserved region of intron 34, which strongly decreased protein expression of Polε1 and also to a lesser extent the Polε2 subunit. We observed impairment in proliferation and G1- to S-phase progression in patients' T lymphocytes. Polε1 depletion also impaired G1- to S-phase progression in B lymphocytes, chondrocytes, and osteoblasts. Our results evidence the developmental impact of a Polε catalytic subunit deficiency in humans and its causal relationship with a newly recognized, inherited disorder.


The spatial dependency of shoulder muscle demands for seated lateral hand force exertions.
As the modern workplace is dominated by submaximal repetitive tasks, knowledge of the effect of task location is important to ensure workers are unexposed to potentially injurious demands imposed by repetitive work in awkward or sustained postures. The purpose of this investigation was to develop a three-dimensional spatial map of the muscle activity for the right upper extremity during laterally directed submaximal force exertions. Electromyographic (EMG) activity was recorded from fourteen muscles surrounding the shoulder complex as the participants exerted 40N of force in two directions (leftward, rightward) at 70 defined locations. Hand position in both push directions strongly influenced total and certain individual muscle demands as identified by repeated measures analysis of variance (P < .001). During rightward exertions individual muscle activation varied from 1 to 21% MVE and during leftward exertions it varied from 1 to 27% MVE with hand location. Continuous prediction equations for muscular demands based on three-dimensional spatial parameters were created with explained variance ranging from 25 to 73%. The study provides novel information for evaluating existing and proactive workplace designs, and may help identify preferred geometric placements of lateral exertions in occupational settings to lower muscular demands, potentially mitigating fatigue and associated musculoskeletal risks.


An estrogen receptor-alpha knock-in mutation provides evidence of ligand-independent signaling and allows modulation of ligand-induced pathways in vivo.
Estrogen-nonresponsive estrogen receptor-alpha (ERalpha) knock-in (ENERKI) mice were generated to distinguish between ligand-induced and ligand-independent ER-alpha actions in vivo. These mice have a mutation [glycine 525 to leucine (G525L)] in the ligand-binding domain of ERalpha, which significantly reduces ERalpha interaction with and response to endogenous estrogens, whereas not affecting growth factor activation of ligand-independent pathways. ENERKI mice had hypoplastic uterine tissues and rudimentary mammary gland ductal trees. Females were infertile due to anovulation, and their ovaries contained hemorrhagic cystic follicles because of chronically elevated levels of LH. The ENERKI phenotype confirmed that ligand-induced activation of ERalpha is crucial in the female reproductive tract and mammary gland development. Growth factor treatments induced uterine epithelial proliferation in ovariectomized ENERKI females, directly demonstrating that ERalpha ligand-independent pathways were active. In addition, the synthetic ERalpha selective agonist propyl pyrazole triol (PPT) and ER agonist diethylstilbestrol (DES) were still able to activate ligand-induced G525L ERalpha pathways in vitro. PPT treatments initiated at puberty stimulated ENERKI uterine development, whereas neonatal treatments were needed to restore mammary gland ductal elongation, indicating that neonatal ligand-induced ERalpha activation may prime mammary ducts to become more responsive to estrogens in adult tissues. This is a useful model for in vivo evaluation of ligand-induced ERalpha pathways and temporal patterns of response. DES did not stimulate an ENERKI uterotrophic response. Because ERbeta may modulate ERalpha activation and have an antiproliferative function in the uterus, we hypothesize that ENERKI animals were particularly sensitive to DES-induced inhibition of ERalpha due to up-regulated uterine ERbeta levels.


Neonatal nosocomial sepsis in a level-III NICU: evaluation of the causative agents and antimicrobial susceptibilities.
Despite advances in supportive care and use of antibiotics, sepsis preserves its importance due to its high mortality and morbidity for neonates. Identifying the causative agents and antibiotic resistance yearly in a neonatal intensive care unit (NICU) helps the physician to choose the most appropriate empirical therapy. In this study we aimed to evaluate positive blood cultures and antibiotic susceptibilities of newborns with proven sepsis during the years 2000-2002 in our NICU. The charts of babies with sepsis were evaluated for clinical characteristics, positive cultures and antimicrobial susceptibilities, retrospectively. Although most of the admitted patients were premature (76.5%), the frequency of proven sepsis was quite low, at 9.1% among 909 newborns. Mortality rate in sepsis was 16%. The most commonly isolated micro-organisms were coagulase-negative staphylococci (CoNS) (31.3%), fungi (19.2%), Staphylococcus aureus (13%) and Klebsiella pneumoniae (10.5%). Methicillin resistance for CoNS was 92.3% and for S. aureus was 72.7%. In the last year, a significant increase in the frequency of Klebsiella pneumoniae (8.3 vs 14.2%), CoNS (27.1 vs 37.1%), Pseudomonas aeruginosa (2.1 vs 8.6%) and fungal infections (18.8 vs 20%) was observed compared to the previous years. An initial empirical antibiotic therapy for late-onset sepsis was designed with teicoplanin + piperacillin-tazobactam/meropenem + antifungal (fluconazole or amphotericin B) as the best combination to cover this spectrum until the culture results arrive. However, this combination is only compatible with our results and may not be applied in all units. Every unit must follow the bacterial spectrum and antibacterial resistance patterns to choose their specific empirical treatment strategy for nosocomial infections.


Tales of cannibalism, suicide, and murder: Programmed cell death in C. elegans.
"Life is pleasant. Death is peaceful. It's the transition that's troublesome," said Isaac Asimov. Indeed, much scientific work over the last hundred years centered around attempts either to stave off or to induce the onset of death, at both the organismal and the cellular levels. In this quest, the nematode C. elegans has proven an invaluable tool, first, in the articulation of the genetic pathway by which programmed cell death proceeds, and also as a continuing source of inspiration. It is our purpose in this Chapter to familiarize the reader with the topic of programmed cell death in C. elegans and its relevance to current research in the fields of apoptosis and cell corpse clearance.


Computed Tomographic Exploration of the Middle Ethmoidal Artery.
Objectives The integral involvement of sinus and skull base surgeries in the field of otolaryngology makes the endonasal vasculature including the ethmoidal arteries important to consider. The anterior ethmoidal artery (AEA) and posterior ethmoidal artery (PEA) are well-known entities, yet the relatively recent notion of accessory or middle ethmoidal vessels complicates our understanding of this arterial system. Study Design Radiographic study. Methods Fifty computed tomographic angiographies were studied for the presence of accessory/middle ethmoidal arteries (MEAs). If contrasted arteries were not visualized reliably, foramina were accepted as evidence of arteries. The accessory arteries/foramina were then compared with the locations of the AEA and PEA. Results A total of 19 of the 50 patient samples studied had evidence of a right, left, or bilateral middle ethmoidal vessels (38%). Overall, 26 arteries total were identified out of the 100 sides (26%). Unilateral middle arteries were more common than bilateral, and right sided were more common than left. There was no evidence of multiple MEAs on a given side. Conclusion The endonasal surgeon must be cognizant of the possible presence of MEAs. These arteries should be considered when working in the medial orbit and anterior skull base region.


Are we going about chemical risk assessment for the aquatic environment the wrong way?
The goal of protecting the aquatic environment through testing thousands of chemicals against hundreds of aquatic species with thousands of endpoints while also considering mixtures is impossible given the present resources. Much of the impetus for studies on micropollutants, such as pharmaceuticals, came from the topic of endocrine disruption in wild fish. But despite concern over reductions in fish fertility, there is little evidence that fish populations are in peril. Indeed, fish biologists suggest that many cyprinid populations have been recovering for the past 30 to 40 yr. The central assumption, key to current risk assessment, that effects observed in the laboratory or predicted by models are readily transferrable to the population level, is therefore questionable. The neglect in monitoring wildlife populations is the key weakness in environmental protection strategies. If we do not know whether aquatic wildlife species are declining or increasing, how valuable are our other ecotoxicological activities? Environ Toxicol Chem 2016;35:1609-1616. © 2016 SETAC.


Classical Conditioning Differences Associated With Chronic Pain: A Systematic Review.
Prominent clinical models of chronic pain propose a fundamental role of classical conditioning in the development of pain-related disability. If classical conditioning is key to this process, then people with chronic pain may show a different response to pain-related conditioned stimuli than healthy control subjects. We set out to determine whether this is the case by undertaking a comprehensive and systematic review of the literature. To identify studies comparing classical conditioning between people with chronic pain and healthy control subjects, the databases MEDLINE, PsychINFO, PsychARTICLES, Scopus, and CINAHL were searched using key words and medical subject headings consistent with 'classical conditioning' and 'pain.' Articles were included when: 1) pain-free control and chronic pain groups were included, and 2) a differential classical conditioning design was used. The systematic search revealed 7 studies investigating differences in classical conditioning between people with chronic pain and healthy control participants. The included studies involved a total of 129 people with chronic pain (fibromyalgia syndrome, spinal pain, hand pain, irritable bowel syndrome), and 104 healthy control participants. Outcomes included indices of pain-related conditioning such as unconditioned stimulus (US) expectancy and contingency awareness, self-report and physiological measures of pain-related fear, evaluative judgements of conditioned stimulus pleasantness, and muscular and cortical responses. Because of variability in outcomes, meta-analyses included a maximum of 4 studies. People with chronic pain tended to show reduced differential learning and flatter generalization gradients with respect to US expectancy and fear-potentiated eyeblink startle responses. Some studies showed a propensity for greater muscular responses and perceptions of unpleasantness in response to pain-associated cues, relative to control cues. The review revealed preliminary evidence that people with chronic pain may exhibit less differential US expectancy and fear learning. This characteristic may contribute to widespread fear-avoidance behavior. The assumption that altered classical conditioning may be a predisposing or maintaining factor for chronic pain remains to be verified.


Is Vitamin D Supplementation Effective for Low Back Pain? A Systematic Review and Meta-Analysis.
Low back pain (LBP) is the leading cause of years lived with disability worldwide. Current intervention strategies are failing to reduce the enormous global burden of LBP and are prompting researchers to investigate alternative management strategies, such as vitamin D supplementation. Vitamin D supplementation appears to down regulate pro-inflammatory cytokines which lead to pain and up regulate anti-inflammatory cytokines that reduce inflammation. These mechanisms might explain the increasing interest in the use of vitamin D supplementation for LBP. To determine whether vitamin D supplementation improves pain more than a control intervention for individuals with LBP. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We performed searches in numerous electronic databases combining key words relating to "vitamin D" and "LBP" until March 2017. Studies were included if they investigated vitamin D supplementation in participants with LBP, provided there was a comparison intervention. There was no restriction on the type of LBP, the intervention parameters investigated, or the type of clinical trial (e.g., randomized, non-randomized). Two reviewers independently performed the selection of studies, extracted data, rated the methodological quality of the included studies, and evaluated the overall quality of the evidence using the Grading of Recommendations Assessment, Delevopment, and Evaulation (GRADE) approach. After screening 3,534 articles, 8 clinical trials were included in this systematic review. There is very low quality evidence (based on the GRADE approach) that vitamin D supplementation is not more effective than any intervention (including placebo, no intervention, and other conservative/pharmacological interventions) (continuous pain measures [0-100]: mean difference [MD] = -2.65, 95% confidence interval [CI]: -10.42 to 5.12, P = 0.504, n = 5; self-reported reduction in pain: pooled odds ratio [OR] = 1.07, 95% CI: 0.35 to 3.26, P = 0.906, n = 5) or placebo/no intervention for individuals with LBP (continuous pain measures: MD = 1.29, 95% CI: -3.81 to 6.39, P = 0.620, n = 4; self-reported reduction in pain: pooled OR = 1.53, 95% CI: 0.38 to 6.20, P = 0.550, n = 4), where 'n' is the number of studies included in the meta-analysis. These results did not change when we stratified the meta-analyses by the type of vitamin supplementation (vitamin D3 vs. alfacalcidol) or the type of LBP (non-specific vs. LBP resulting from osteoporosis or vertebral fractures). The overall quality of evidence was "very low" due to the poor methodological quality and small sample sizes of the included studies. Vitamin D supplementation is not more effective than placebo, no intervention, or other conservative/pharmacological interventions for LBP (based on very low quality evidence). These results are consistent, regardless of the type of LBP or vitamin D supplementation. Until well-designed and adequately powered clinical trials suggest otherwise, the prescription of vitamin D for LBP cannot be recommended. PROSPERO Registration No: CRD42016046874. www.crd.york.ac.uk/PROSPERO/display_record.asp?ID = CRD42016046874. Vitamin D, low back pain, chronic low back pain, alfacalcidol, osteoporosis, vertebral fractures, serum 25-hydroxyvitamin D, systematic review.


High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases.
In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml.


Students' mental health clinical placements, clinical confidence and stigma surrounding mental illness: A correlational study.
Theory and clinical practicum in mental health are an important component for students in most nursing curriculum. Some studies have shown that knowledge and confidence in caring for people with mental illness improve after mental health clinical placements while others had contrasting results. Our study examined the relationship between clinical placement, confidence and stigma surrounding mental illness. We undertook a cross-sectional, descriptive correlational study in a sample of 144 undergraduate nursing students in Singapore who had completed their theoretical and clinical practicum in mental health using the Clinical Placement Survey Clinical Confidence Scale and Social Distance Scale. Descriptive, correlations and multiple regression were used to analyse the data. The results showed the mean scores for the social distance scale, clinical confidence scale and clinical placement survey were 19.92 out of 35, 49.29 out of 80 and 103.43 out of 154 respectively. Attitudes toward clinical placement experiences were significantly correlated with both stigmatising attitudes and clinical confidence of which, intentions of working in mental health settings were specifically significantly associated with stigmatising attitudes and attitudes toward clinical placement experiences, with emphasis on greater sense of preparedness, lesser perceived anxiety and greater preference for a future career in mental health nursing. This study highlighted the need to improve current mental health clinical placements to better build nursing students' confidence in caring for mentally ill patients. The interest toward specialising in mental health nursing is still lacking in nursing undergraduate students despite mental health clinical placements.


Effects of pre- and postnatal nutrition interventions on child growth and body composition: the MINIMat trial in rural Bangladesh.
Nutritional insults and conditions during fetal life and infancy influence subsequent growth and body composition of children. Effects of maternal food and micronutrient supplementation and exclusive breastfeeding counseling on growth of offspring aged 0-54 months and their body composition at 54 months of age were studied. In the MINIMat trial (ISRCTN16581394) in Matlab, Bangladesh, pregnant women were randomized to early (around 9 weeks) or usual invitation (around 20 weeks) to food supplementation and to one of the three daily micronutrient supplements: 30-mg Fe and 400-µg folic acid (Fe30F), 60-mg Fe and 400-µg folic acid (Fe60F), and multiple micronutrient supplements (MMS). The supplements were also randomized to exclusive breastfeeding (EBF) counseling or to usual health messages. No differences in background characteristics were observed among the intervention groups. There was also no differential effect of prenatal interventions on birthweight or birthlength. Early food supplementation reduced the level of stunting from early infancy up to 54 months of age among boys (average difference - 6.5% units, 95% confidence interval [CI] 1.7-11.3, p=0.01) but not among girls (average difference - 2.4% units, 95% CI -2.2-7.0, p=0.31). MMS resulted in more stunting compared to standard Fe60F (average difference - 4.8% units, 95% CI 0.8-8.9, p=0.02). Breastfeeding counseling prolonged the duration of EBF (difference - 35 days, 95% CI 30.6-39.5, p<0.001). Neither pregnancy interventions nor breastfeeding counseling influenced the body composition of children at 54 months of age. Early food supplementation during pregnancy reduced the occurrence of stunting among boys aged 0-54 months, while prenatal MMS increased the proportion of stunting. Food and micronutrient supplementation or EBF intervention did not affect body composition of offspring at 54 months of age. The effects of prenatal interventions on postnatal growth suggest programming effects in early fetal life.


Conjugating phosphospermines to siRNAs for improved stability in serum, intracellular delivery and RNAi-mediated gene silencing.
siRNAs are usually formulated with cationic polymers or lipids to form supramolecular particles capable of binding and crossing the negatively charged cell membrane. However, particles hardly diffuse through tissues when administered in vivo. We therefore are developing cationic siRNAs, composed of an antisense sequence annealed to an oligophosphospermine-conjugated sense strand. Cationic siRNAs have been previously shown to display gene silencing activity in human cell line (Nothisen et al. J. Am. Chem. Soc.2009). We have improved the synthesis, purification and characterization of oligospermine-oligoribonucleotide conjugates which provide cationic siRNAs with enhanced biological activity. We show data supporting their carrier-free intracellular delivery in a molecular, soluble state. Additional results on the relationship between global charge, uptake and silencing activity confirm the requirement for an overall positive charge of the conjugated siRNA in order to enter cells. Importantly, conjugated siRNAs made of natural phosphodiester nucleotides are protected from nuclease degradation by the oligophosphospermine moiety, operate through the RNAi mechanism and mediate specific gene silencing at submicromolar concentration in the presence of serum.


Albuminuria is associated with a higher prevalence of depression in a population-based cohort study: the Maastricht Study.
Depression is common in individuals with chronic kidney disease (CKD). However, data on the association of albuminuria, which together with reduced estimated glomerular filtration rate (eGFR) defines CKD, with depression are scarce and conflicting. In addition, it is not clear when in the course from normal kidney function to CKD the association with depression appears. We examined the cross-sectional associations of albuminuria and eGFR with depressive symptoms and depressive episodes in 2872 and 3083 40- to 75-year-old individuals, respectively, who completed the baseline survey of an ongoing population-based cohort study conducted in the southern part of The Netherlands between November 2010 and September 2013. Urinary albumin excretion (UAE) was the average UAE in two 24-h urine collections and eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation based on creatinine and cystatin C. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the presence of a minor or major depressive episode was assessed with the MINI-International Neuropsychiatric Interview. In total, 5.4% had a minor or major depressive episode. UAE was <15 mg/24 h in 81.2%, 15-<30 mg/24 h in 10.3% and ≥30 mg/24 h in 8.6%. In a multivariable logistic regression analysis adjusted for potential confounders, and with UAE <15 mg/24 h as reference category, the odds ratio for a minor or major depressive episode was 2.13 [95% confidence interval (CI) 1.36-3.36] for UAE 15-<30 mg/24 h and 1.81 (95% CI 1.10-2.98) for UAE ≥30 mg/24 h. The average eGFR was 88.2 ± 14.7 mL/min/1.73 m2. eGFR was not associated with the presence of a minor or major depressive episode. Results were similar when we assessed associations with depressive symptoms or clinically relevant depressive symptoms (PHQ-9 score ≥10). Albuminuria was associated with depressive symptoms and depressive episodes, even at levels of UAE that do not fulfil the CKD criteria. Future longitudinal studies should examine the direction of this association and whether albuminuria could serve as a biomarker to identify individuals at risk of depression.


Assessment of Kuwait's Al-Qurain landfill using remotely sensed data.
Kuwait's Al-Qurain landfill problem resulted from indiscriminate dumping of domestic and industrial waste in an abandoned quarry in the late 1970s and early 1980s. The landfill and surrounding areas were set aside for a government housing project without an environmental assessment of the impact of the landfill on the project. Inhabitants of the newly constructed housing area experienced persistent foul odor emanating from the landfill site. Since then, the issue has generated a lot of public interests, and several remediation measures have been adopted. In this preliminary study, several remotely sensed data consisting of Landsat Multispectral Scanner (MSS), Landsat Thematic Mapper (TM), IKONOS, and synthetic aperture radar (SAR) acquired between 1972 and 2000 were processed and assessed for their usefulness to study and monitor the landfill site. The imagery provided a historical perspective of how the areas had changed over the last 30 years. Other useful information of the landfill obtained from the satellite imagery included the spatial extent, spectral reflectance, surface temperature, and surface roughness. The landfill site showed higher surface temperatures compared to the immediate surrounding areas-a process that could accelerate the biodegradation and the release of landfill gases. Such dataset could be incorporated into a GIS for the long-term monitoring of the site.


Comparison of PCR and quantitative real-time PCR methods for the characterization of ruminant and cattle fecal pollution sources.
The State of California has mandated the preparation of a guidance document on the application of fecal source identification methods for recreational water quality management. California contains the fifth highest population of cattle in the United States, making the inclusion of cow-associated methods a logical choice. Because the performance of these methods has been shown to change based on geography and/or local animal feeding practices, laboratory comparisons are needed to determine which assays are best suited for implementation. We describe the performance characterization of two end-point PCR assays (CF128 and CF193) and five real-time quantitative PCR (qPCR) assays (Rum2Bac, BacR, BacCow, CowM2, and CowM3) reported to be associated with either ruminant or cattle feces. Each assay was tested against a blinded set of 38 reference challenge filters (19 duplicate samples) containing fecal pollution from 12 different sources suspected to impact water quality. The abundance of each host-associated genetic marker was measured for qPCR-based assays in both target and non-target animals and compared to quantities of total DNA mass, wet mass of fecal material, as well as Bacteroidales, and enterococci determined by 16S rRNA qPCR and culture-based approaches (enterococci only). Ruminant- and cow-associated genetic markers were detected in all filters containing a cattle fecal source. However, some assays cross-reacted with non-target pollution sources. A large amount of variability was evident across laboratories when protocols were not fixed suggesting that protocol standardization will be necessary for widespread implementation. Finally, performance metrics indicate that the cattle-associated CowM2 qPCR method combined with either the BacR or Rum2Bac ruminant-associated methods are most suitable for implementation.


CT quality assurance in the lung screening study component of the National Lung Screening Trial: implications for multicenter imaging trials.
The purpose of this study was to describe the effect of implementing an imaging quality assurance program on CT image quality in the Lung Screening Study component of the National Lung Screening Trial. The National Lung Screening Trial is a multicenter study in which 53,457 subjects at increased risk of lung cancer were randomized to undergo three annual chest CT or radiographic screenings for lung cancer to determine the relative effect of use of the two screening tests on lung cancer mortality. Of the 26,724 subjects randomized to the CT screening arm of the National Lung Screening Trial, the Lung Screening Study randomized 17,309 through 10 screening centers. The others were randomized through the American College of Radiology Imaging Network. Quality assurance procedures were implemented that included centralized review of a random sample of 1,504 Lung Screening Study CT examinations. Quality defect rates were tabulated. Quality defect rates ranged from 0% (section reconstruction interval) to 7.1% (reconstructed field of view), and most errors were sporadic. However, a recurrently high effective tube current-time product setting at one center, excessive streak artifact at one center, and excessive section thickness at one center were detected and corrected through the quality assurance process. Field-of-view and scan length errors were less frequent over the second half of the screening period (p < 0.01 for both parameters, two-tailed, paired Student's t test). Error rates varied among the screening centers and reviewers for most parameters evaluated. Our experience suggested that centralized monitoring of image quality is helpful for reducing quality defects in multicenter trials.


Nucleofection mediates high-efficiency stable gene knockdown and transgene expression in human embryonic stem cells.
High-efficiency genetic modification of human embryonic stem (hES) cells would enable manipulation of gene activity, routine gene targeting, and development of new human disease models and treatments. Chemical transfection, nucleofection, and electroporation of hES cells result in low transfection efficiencies. Viral transduction is efficient but has significant drawbacks. Here we describe techniques to transiently and stably express transgenes in hES cells with high efficiency using a widely available vector system. The technique combines nucleofection of single hES cells with improved methods to select hES cells at clonal density. As validation, we reduced Oct4 and Nanog expression using siRNAs and shRNA vectors in hES cells. Furthermore, we derived many hES cell clones with either stably reduced alkaline phosphatase activity or stably overexpressed green fluorescent protein. These clones retained stem cell characteristics (normal karyotype, stem cell marker expression, self-renewal, and pluripotency). These studies will accelerate efforts to interrogate gene function and define the parameters that control growth and differentiation of hES cells. Disclosure of potential conflicts of interest is found at the end of this article.


Men's experiences of early life trauma and pathways into long-term homelessness.
Previous studies that have explored the association between childhood trauma and homelessness indicate that traumatic events can lead to survivor distrust of interpersonal relationships and institutions, prolonged homelessness and poor health and social outcomes. The majority of this literature relies on quantitative data and fails to investigate the personal experiences of childhood trauma that are found to impact housing status later in life. Semi-structured, qualitative interviews were conducted with 25 men living in an urban area in Ontario who had spent more than 30 consecutive nights in an emergency shelter over the course of their housing histories. During data analysis, it was observed that all of the men had experienced some form of trauma or neglect in childhood which contributed to their entries into homelessness. Using a case study approach, three entry pathways into long term homelessness are described: 1) youth; 2) emerging or early adulthood; and 3) middle adulthood. Participants are classified into the pathways by the developmental period at which they first entered homelessness. These findings have implications for policy makers and service providers, as key intervention points are identified. Establishing effective interventions that address crises experienced at these points could assist with homelessness prevention across the life course.


Patient Participation in the Development of a Customized M-Health Intervention to Improve Medication Adherence in Poorly Adherent Individuals with Bipolar Disorder (BD) and Hypertension (HTN).
Individuals living with bipolar disorder (BD) have poorer management of chronic medical conditions such as hypertension (HTN), and worse treatment adherence than the general population. The study objective was to obtain information from patients with both BD and HTN that would inform the development of an m-Health intervention to improve medication adherence for poorly adherent individuals living with both these chronic illnesses. Focus group methodology was used to collect information from 13 participants on perceived barriers and facilitators to BD and HTN medication adherence, as well as feedback on the demonstration and use of a bidirectional text messaging system for medication reminders. Focus groups were audiotaped, transcribed verbatim, and analyzed using content analysis with an emphasis on dominant themes. Forgetfulness was the most frequently mentioned barrier to taking antihypertensive medications, and decisions about taking them were often influenced by BD mood fluctuations and the burden of having to take "too many pills" for both chronic illnesses. Participants' feedback about the use of a text-messaging system to help with medication adherence for BD and HTN was very positive, and their suggestions for modification were incorporated into a more customized system for testing in a Phase 2 trial. Our findings indicate that patient engagement in the development of an m-health intervention has the potential to improve adherence with both BD and HTN medications in individuals with known sub-optimal adherence. Patient engagement in health care is essential if we are to optimize patient outcomes.


The ward atmosphere important for the psychosocial work environment of nursing staff in psychiatric in-patient care.
The nursing staff working in psychiatric care have a demanding work situation, which may be reflected in how they view their psychosocial work environment and the ward atmosphere. The aims of the present study were to investigate in what way different aspects of the ward atmosphere were related to the psychosocial work environment, as perceived by nursing staff working in psychiatric in-patient care, and possible differences between nurses and nurse assistants. 93 nursing staff working at 12 general psychiatric in-patient wards in Sweden completed two questionnaires, the Ward Atmosphere Scale and the QPSNordic 34+. Data analyses included descriptive statistics, the Mann-Whitney U-test, Spearman rank correlations and forward stepwise conditional logistic regression analyses. The data revealed that there were no differences between nurses and nurse assistants concerning perceptions of the psychosocial work environment and the ward atmosphere. The ward atmosphere subscales Personal Problem Orientation and Program Clarity were associated with a psychosocial work environment characterized by Empowering Leadership. Program Clarity was related to the staff's perceived Role Clarity, and Practical Orientation and Order and Organization were positively related to staff perceptions of the Organizational Climate. The results from the present study indicate that several ward atmosphere subscales were related to the nursing staff's perceptions of the psychosocial work environment in terms of Empowering Leadership, Role Clarity and Organizational Climate. Improvements in the ward atmosphere could be another way to accomplish improvements in the working conditions of the staff, and such improvements would affect nurses and nurse assistants in similar ways.


Spontaneous pneumothorax in the third trimester of pregnancy.
The present report concerns a young woman previously diagnosed as having childhood asthma who presented with a secondary spontaneous pneumothorax during the third trimester of pregnancy; at term a caesarean section was recommended for safety reasons. Post partum a severe fixed ventilatory defect unresponsive to inhaled bronchodilator and a short oral course of steroids ruled out asthma. Diffuse bronchiectasis was found on her chest CT scan, although this was not evident clinically. Known aetiologies for diffuse bronchiectasis (cystic fibrosis, anti-α1 antitrypsin deficiency, rheumatic diseases, mycobacterial infections, childhood infections and immune deficiencies) were ruled out. Therefore it is believed her bronchiectasis was idiopathic or congenital. No recommendations from recent guidelines on how to manage labour in a woman after a spontaneous pneumothorax could be found. However, a literature search revealed that pregnant women usually experience primary pneumothorax and may continue in natural labour; however, it is unknown how best to manage a woman with secondary spontaneous pneumothorax.


Extremely late recurrences (≥3 years) of atrioventricular nodal reentrant tachycardia: Electrophysiological characteristics of the index and repeat ablation procedures.
Catheter ablation is an effective treatment for atrioventricular nodal reentrant tachycardia (AVNRT). However, the characteristics of extremely late (>3 years) recurrences of AVNRT after a successful initial ablation are not fully elucidated. We aimed to explore the electrophysiological characteristics of extremely late recurrences of AVNRT after a successful ablation. From 1991 to 2018, 3311 patients (mean age: 48.7 ± 17.4 years; men: 1328 [40.1%]) who underwent catheter ablation for AVNRT were investigated. Baseline characteristics of the patients, recurrence status, and detailed electrophysiological parameters of the index and repeat ablation procedures were obtained for analysis. After a mean follow-up period of 129.5 ± 58.0 months, 65 (2.0%) patients underwent repeat ablation for recurrences of AVNRT, of whom 17 (0.5%) presented with extremely late recurrences. The incidence of transient AV block was significantly higher in patients with extremely late recurrences (5.9%) than in those without recurrences (1.9%) but lower than that in patients with recurrences within <3 years (12.5%, P < .001). In addition, among patients with extremely late recurrences of AVNRT, the atrial-His bundle interval was significantly longer (99.1 ± 23.4 vs. 76.5 ± 13.1 ms, P < .01) and the need for intravenous isoproterenol and/or atropine for the induction of AVNRT (88.2% vs. 47.1%, P = .03) was higher in the repeat ablation procedure than in the index ablation procedure. Recurrences of AVNRT can occur 3 years after a successful initial ablation. The electrophysiological features of the index and repeat ablation procedures differed between patients with extremely late recurrences of AVNRT and those with recurrences within <3 years.


Arabinogalactan biosynthesis: Implication of AtGALT29A enzyme activity regulated by phosphorylation and co-localized enzymes for nucleotide sugar metabolism in the compartments outside of the Golgi apparatus.
Arabinogalactan proteins are abundant cell surface proteoglycans in plants and are implicated to act as developmental markers during plant growth. We previously reported that AtGALT31A, AtGALT29A, and AtGLCAT14A-C, which are involved in the biosynthesis of arabinogalactan proteins, localize not only to the Golgi cisternae but also to smaller compartments, which may be a part of the unconventional protein secretory pathway in plants. In Poulsen et al., (1) we have demonstrated increased targeting of AtGALT29A to small compartments when Y144 is substituted with another amino acid, and we implicated a role for Y144 in the subcellular targeting of AtGALT29A. In this paper, we are presenting another aspect of Y144 substitution in AtGALT29A; namely, Y144A construct demonstrated a 2.5-fold increase while Y144E construct demonstrated a 2-fold decrease in the galactosyltransferase activity of AtGALT29A. Therefore, the electrostatic status of Y144, which is regulated by an unknown kinase/phosphatase system, may regulate AtGALT29A enzyme activity. Moreover, we have identified additional proteins, apyrase 3 (APY3; At1g14240) and UDP-glucuronate epimerases 1 and 6 (GAE1, At4g30440; GAE6, At3g23820), from Arabidopsis thaliana that co-localize with AtGALT31A in the small compartments when expressed transiently in Nicotiana benthamiana. These proteins may play roles in nucleotide sugar metabolism in the small compartments together with arabinogalactan glycosyltransferases.


Tunable Self-Assembly and Morphology-Dependent Photoconductivity of a Donor-Acceptor-Structured Diruthenium Complex.
A donor-acceptor-structured diruthenium complex, 1(PF6)4, that contains an electron-deficient bridging ligand and electron-rich distal diarylamines modified with long aliphatic chains has been synthesized. By varying the solvent environments and assembly conditions, we obtained three different self-assembled nanostructures of 1(PF6)4, including zero-dimensional nanospheres, one-dimensional nanofibers, and thin films with interconnected nanowire networks. These structures were investigated by scanning electron microscopy, transmission electron microscopy, dynamic light scattering, X-ray diffraction, and atomic force microscopy (AFM) analysis. Conductive AFM analysis shows that the nanowire networks exhibit a high conductivity of 0.023 S/cm and an enhanced photoconductivity of 0.59 S/cm under visible light irradiation.


Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations.
The American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort risk equations were developed to estimate atherosclerotic cardiovascular disease (CVD) risk and guide statin initiation. To assess calibration and discrimination of the Pooled Cohort risk equations in a contemporary US population. Adults aged 45 to 79 years enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between January 2003 and October 2007 and followed up through December 2010. We studied participants for whom atherosclerotic CVD risk may trigger a discussion of statin initiation (those without clinical atherosclerotic CVD or diabetes, low-density lipoprotein cholesterol level between 70 and 189 mg/dL, and not taking statins; n = 10,997). Predicted risk and observed adjudicated atherosclerotic CVD incidence (nonfatal myocardial infarction, coronary heart disease [CHD] death, nonfatal or fatal stroke) at 5 years because REGARDS participants have not been followed up for 10 years. Additional analyses, limited to Medicare beneficiaries (n = 3333), added atherosclerotic CVD events identified in Medicare claims data. There were 338 adjudicated events (192 CHD events, 146 strokes). The observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a 10-year predicted atherosclerotic CVD risk of less than 5% was 1.9 (95% CI, 1.3-2.7) and 1.9, respectively, risk of 5% to less than 7.5% was 4.8 (95% CI, 3.4-6.7) and 4.8, risk of 7.5% to less than 10% was 6.1 (95% CI, 4.4-8.6) and 6.9, and risk of 10% or greater was 12.0 (95% CI, 10.6-13.6) and 15.1 (Hosmer-Lemeshow χ2 = 19.9, P = .01). The C index was 0.72 (95% CI, 0.70-0.75). There were 234 atherosclerotic CVD events (120 CHD events, 114 strokes) among Medicare-linked participants and the observed and predicted 5-year atherosclerotic CVD incidence per 1000 person-years for participants with a predicted risk of less than 7.5% was 5.3 (95% CI, 2.8-10.1) and 4.0, respectively, risk of 7.5% to less than 10% was 7.9 (95% CI, 4.6-13.5) and 6.4, and risk of 10% or greater was 17.4 (95% CI, 15.3-19.8) and 16.4 (Hosmer-Lemeshow χ2 = 5.4, P = .71). The C index was 0.67 (95% CI, 0.64-0.71). In this cohort of US adults for whom statin initiation is considered based on the ACC/AHA Pooled Cohort risk equations, observed and predicted 5-year atherosclerotic CVD risks were similar, indicating that these risk equations were well calibrated in the population for which they were designed to be used, and demonstrated moderate to good discrimination.


Case series of individuals with analytically confirmed acute mephedrone toxicity.
Previous reports of acute toxicity/harm associated with mephedrone use have been based on self-reported mephedrone use; toxicological screening has not been undertaken in these cases to determine whether mephedrone has been used. To report the first case series of analytically confirmed mephedrone-related acute toxicity. Serum samples were collected from individuals presenting to an emergency department (ED) with acute toxicity related to self-reported mephedrone use. Toxicological analysis, by gas-chromatography coupled with mass-spectrometry and liquid chromatography with tandem mass-spectrometry was performed to qualitatively confirm mephedrone use. Symptoms/signs of acute mephedrone toxicity and basic physiological parameters were extracted from the routine ED records. Acute mephedrone-related toxicity was analytically confirmed in seven male patients; the mean ± SD age was 24.6 ± 6.5 years (range 16-36 years). Agitation (four patients) was the most common symptom/sign reported; other common symptoms/signs included: palpitations (two patients); chest pain (two patients); self-limiting pre-hospital seizures (one patient) and headaches (one patient). The mean heart rate was 109.1 ± 21.8 (range 80-140) beats per minute; one patient had a "severe" tachycardia (heart rate of ≥ 140 bpm). The mean systolic blood pressure was 153.0 ± 39.6 (range 110-210) mmHg; three patients had clinically significant hypertension (systolic blood pressure ≥ 160 mmHg). These analytically confirmed acute mephedrone toxicity presentations had clinical features of toxicity consistent with an acute sympathomimetic toxidrome (e.g. hypertension, tachycardia and agitation). These findings are similar to the pattern of toxicity seen with other sympathomimetic recreational drugs such as 3,4-Methylenedioxymethamphetamine (MDMA) and cocaine. The process for determining whether a novel psychoactive substance should be controlled often relies on demonstrated/proven acute harm associated with its use. It is important that clinical toxicologists undertake appropriate biological sampling and toxicological analyses in suspected cases of "novel psychoactive drug" toxicity. This will ensure that both clinicians and legislative authorities are informed of the confirmed pattern of toxicity associated with these drugs.


Camera Calibration for Water-Biota Research: The Projected Area of Vegetation.
Imaging systems have an indisputable role in revealing vegetation posture under diverse flow conditions, image sequences being generated with off the shelf digital cameras. Such sensors are cheap but introduce a range of distortion effects, a trait only marginally tackled in hydraulic studies focusing on water-vegetation dependencies. This paper aims to bridge this gap by presenting a simple calibration method to remove both camera lens distortion and refractive effects of water. The effectiveness of the method is illustrated using the variable projected area, computed for both simple and complex shaped objects. Results demonstrate the significance of correcting images using a combined lens distortion and refraction model, prior to determining projected areas and further data analysis. Use of this technique is expected to increase data reliability for future work on vegetated channels.


Osteoclasts are capable of particle phagocytosis and bone resorption.
Osteoclasts are multinucleated cells specialized for the function of lacunar bone resorption. Although they are known to be capable of phagocytosis of inert particles, it is not known whether this abolishes their ability to respond to hormones or to form resorption lacunae. Human and rat osteoclasts were isolated from giant cell tumours of bone and rat long bones, respectively, and cultured on coverslips and cortical bone slices, both in the presence and in the absence of particles of latex (1 micron diameter) and polymethylmethacrylate (PMMA) (< 50 microns). By light microscopy, it was evident that osteoclasts which had phagocytosed both latex and PMMA particles remained responsive to calcitonin. Osteoclast phagocytosis of particles was also evident on scanning electron microscopy, where it could also be seen that these cells were associated with the formation of resorption lacunae. These findings underline the fact that the osteoclast is a true member of the mononuclear phagocyte system and that phagocytosis does not abrogate either its hormonal response to calcitonin or its highly specialized function of bone resorption. That osteoclasts which have phagocytosed biomaterial particles such as PMMA are still able to carry out lacunar bone resorption is of interest in clinical conditions such as aseptic loosening, where a heavy foreign body particle load is often associated with extensive bone resorption.


A lifelong learning hyper-heuristic method for bin packing.
We describe a novel hyper-heuristic system that continuously learns over time to solve a combinatorial optimisation problem. The system continuously generates new heuristics and samples problems from its environment; and representative problems and heuristics are incorporated into a self-sustaining network of interacting entities inspired by methods in artificial immune systems. The network is plastic in both its structure and content, leading to the following properties: it exploits existing knowledge captured in the network to rapidly produce solutions; it can adapt to new problems with widely differing characteristics; and it is capable of generalising over the problem space. The system is tested on a large corpus of 3,968 new instances of 1D bin-packing problems as well as on 1,370 existing problems from the literature; it shows excellent performance in terms of the quality of solutions obtained across the datasets and in adapting to dynamically changing sets of problem instances compared to previous approaches. As the network self-adapts to sustain a minimal repertoire of both problems and heuristics that form a representative map of the problem space, the system is further shown to be computationally efficient and therefore scalable.


Effects of analytical and experiential self-focus on stress-induced cognitive reactivity in eating disorder psychopathology.
Previous research suggests distinct modes of self-focus, each with distinct functional properties: Analytical self-focus appears maladaptive, with experiential self-focus having more adaptive effects on indices of cognitive-affective functioning (e.g., Watkins, Moberly, & Moulds, 2008). The authors applied this framework to eating disorder (ED) psychopathology and manipulated the mode of self-focus prior to exposure to a stressor (imagining eating a large meal; Shafran, Teachman, Kerry, & Rachman, 1999). Study 1 showed that students high in ED psychopathology reported lower post-stressor feelings of weight or shape change and less subsequent attempts to neutralise (e.g., imagining exercising) after experiential relative to analytical self-focus. Study 2 found that partially weight restored patients with anorexia nervosa had lower post-stressor estimates of their own weight and reported lower urge to cancel stressor effects following experiential compared to analytical self-focus. Experiential self-focus was also followed by less neutralisation than analytical self-focus. Results suggest that the mode of self-focus affects cognitive reactivity following a stressor in individuals with ED psychopathology. Examining the mode within which individuals with ED psychopathology focus on self and body may raise important implications for understanding of psychopathology and open new possibilities for augmenting current treatments.


Deep Reinforcement Learning for Cyber Security.
The scale of Internet-connected systems has increased considerably, and these systems are being exposed to cyberattacks more than ever. The complexity and dynamics of cyberattacks require protecting mechanisms to be responsive, adaptive, and scalable. Machine learning, or more specifically deep reinforcement learning (DRL), methods have been proposed widely to address these issues. By incorporating deep learning into traditional RL, DRL is highly capable of solving complex, dynamic, and especially high-dimensional cyber defense problems. This article presents a survey of DRL approaches developed for cyber security. We touch on different vital aspects, including DRL-based security methods for cyber-physical systems, autonomous intrusion detection techniques, and multiagent DRL-based game theory simulations for defense strategies against cyberattacks. Extensive discussions and future research directions on DRL-based cyber security are also given. We expect that this comprehensive review provides the foundations for and facilitates future studies on exploring the potential of emerging DRL to cope with increasingly complex cyber security problems.


Psychosocial work characteristics, sleep disturbances and risk of subsequent depressive symptoms: a study of time-varying effect modification.
Job strain and low social support at work are recognized risk factors for depression. However, people with poor sleep may represent a high-risk group more likely to benefit from interventions against work stress. The present study examined whether the associations between these work stressors and depressive symptoms differed by strata of sleep disturbances (effect modification/effect moderation) considering repeat measures of work characteristics and sleep. The study was based on five biennial measurements of the Swedish Longitudinal Occupational Survey of Health, including 1537 respondents recurrently in paid work, from an originally representative sample of the Swedish working population. High work demands, low decision authority and low social support were measured waves 2 and 4, sleep disturbances (putative moderator/modifier) waves 1 and 3, and depressive symptoms (outcome) wave 5. Causal effect modification, whether the effect of working conditions differed by strata of sleep disturbances, was analysed by structural nested mean modelling estimated using a regression-with-residuals with inverse-probability-of-treatment weighting approach. High demands and low social support, but not low decision authority, influenced subsequent depressive symptoms. The relationship between social support and depressive symptoms was not apparently modified by sleep disturbances. However, disturbed sleep wave 3 modified the effect of high demands wave 4 (coefficient 1.77, P < 0.05) on depressive symptoms wave 5. The results indicate that high job demands is a stronger risk factor for depressive symptoms in people with pre-existing sleep disturbances, suggesting that targeted workplace interventions may be more effective when it comes to preventing negative effects of job demands.


Single and repeated infections of grivet monkeys with Schistosoma mansoni: parasitological and pathological observations over a 31-month period.
Groups of 6 to 8 grivet monkeys (Ceropithecus aethiops aethiops), each of which had been exposed to 600 cercariae of Schistosoma mansoni, were killed 3, 6, and 31 months after exposure. Other groups of monkeys were repeatedly challenged with cercariae beginning 4 or 23 months after the initial infection, and were killed 31 months after the first exposure. Peripheral blood leukocytes, eosinophiles, and schistosome eggs passed in the feces were determined during the course of the infection. At autopsy, gross and histopathologic observations were made, worms were recovered by perfusion, and the number of eggs in the tissues was determined by digestion. Monkeys became acutely ill about 8 weeks after the initial exposure, and death was attributed to acute'toxemic' schistosomiasis in 4 of 46 infected animals. The symptoms and signs of the acute phase did not recur with reinfection. Most subsequent natural deaths were caused by Klebsiella infection which occurred in both infected and control monkeys and did not appear to be related to the schistosome infection. Relatively stable infections were found after a single exposure to cercariae, with only a slight decrease in worm numbers and moderate decrease in egg passage after 31 months. With repeated reinfection, only 19% of challenge cercariae developed into adult worms. Oviposition by these worms was delayed and the rate of oviposition was substantially less than in monkeys infected only once. Eggs deposited in the tissues were rapidly destroyed. The calculated rate of oviposition varied from 658 eggs/day per female 3 months after a single infection to 299 eggs/ day per female 31 months after repeated infections. Although very heavy infections were present in repeatedly infected monkeys, only slight hepatic fibrosis was seen and no portal hypertension or portal-systemic collateral circulation developed. Severe intestinal disease was present in only two monkeys. The remaining animals had little diarrhea after the acute phase, and there was only slight loss of plasma protein into the feces 31 months after exposure.


A new species of mermithid (Nematoda) in chironomids eclosing from a northern Minnesota bog.
Hydromermis haggardi n. sp. (Nematoda: Mermithidae) is described from the hemocoel of chironomid imagos eclosing from Lake Alice Bog in northern Minnesota in June and July 2007. The species is distinguished from the other 27 described members of the genus by the subventral mouth, tulip shape to anterior end of esophagus, colorless vesicular trophosome, single nonbifurcated spicule, short body lengths of both males and females, structure of the S-shaped vagina, decrease in body width at vulva, brevity of postparasitic stage, and the greater development of a posterior ventral protractor muscle in the males. An anomalous adult male bearing large oval structures in the posterior testis is reported. Evidence is presented for the developmental interaction of the new species with Lanceimermis palustris Johnson and Kleve, 2004.


Influenza infection control guidance provided to staff at Veterans Affairs facilities for veterans with spinal cord injury during a pandemic(†).
To assess guidance provided to staff at Veterans Affairs (VA) healthcare facilities on H1N1 influenza infection control for veterans with spinal cord injuries and disorders (SCI/D). Cross-sectional qualitative semi-structured interviews. Thirty-three VA healthcare facilities from throughout the United States that provide care to veterans with SCI/D. Thirty-three infection control key informants, each representing a VA healthcare facility. None. Infection control practices, including vaccination practices, hospital preparedness, and recommendations for future pandemics, both in general and specifically to SCI/D. Most (n = 26, 78.8%) infection control key informants believed veterans with SCI/D were at increased risk for influenza and complications, but only 17 (51.5%) said veterans with SCI/D were treated as a priority group for vaccination at their facilities. There was little special guidance provided for treating veterans with SCI/D, and most (n = 28, 84.8%) informants said that infection control procedures and recommendations were applied universally. Yet, 10 key informants discussed 'unique challenges' to infection control in the SCI/D population. Informants discussed the potential for infectious agents to be spread through shared and common use equipment and the necessity of including caregivers in any vaccination or educational campaigns. Greater input by experts knowledgeable about SCI/D is recommended to adequately address pandemic influenza within healthcare facilities where individuals with SCI/D receive care.


Glutamatergic input to the lateral hypothalamus stimulates ethanol intake: role of orexin and melanin-concentrating hormone.
Glutamate (GLUT) in the lateral hypothalamus (LH) has been suggested to mediate reward behaviors and may promote the ingestion of drugs of abuse. This study tested the hypothesis that GLUT in the LH stimulates consumption of ethanol ( EtOH ) and that this effect occurs, in part, via its interaction with local peptides, hypocretin/orexin (OX), and melanin-concentrating hormone (MCH). In Experiments 1 and 2, male Sprague-Dawley rats, after being trained to drink 9% EtOH , were microinjected in the LH with N-methyl-d-aspartate (NMDA) or its antagonist, D-AP5, or with alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid (AMPA) or its antagonist, CNQX-ds. Consumption of EtOH , chow, and water was then measured. To provide an anatomical control, a separate set of rats was injected 2 mm dorsal to the LH. In Experiment 3, the effect of LH injection of NMDA and AMPA on the expression of OX and MCH was measured using radiolabeled in situ hybridization (ISH) and also using digoxigenin-labeled ISH, to distinguish effects on OX and MCH cells in the LH and the nearby perifornical area (PF) and zona incerta (ZI). When injected into the LH, NMDA and AMPA both significantly increased EtOH intake while having no effect on chow or water intake. The GLUT receptor antagonists had the opposite effect, significantly reducing EtOH consumption. No effects were observed with injections 2 mm dorsal to the LH. In addition to these behavioral effects, LH injection of NMDA significantly stimulated expression of OX in both the LH and PF while reducing MCH in the ZI, whereas AMPA increased OX only in the LH and had no effect on MCH. Glutamatergic inputs to the LH, acting through NMDA and AMPA receptors, appear to have a stimulatory effect on EtOH consumption, mediated in part by increased OX in LH and PF and reduced MCH in ZI.


A randomized controlled trial of a hospital at home service for the terminally ill.
This study evaluated the impact of a Cambridge hospital at home service (CHAH) on patients' quality of care, likelihood of remaining at home in their final 2 weeks of life and general practitioner (GP) visits. The design was a randomized controlled trial, comparing CHAH with standard care. The patient's district nurse, GP and informal carer were surveyed within 6 weeks of patient's death, and 225 district nurses, 194 GPs and 144 informal carers of 229 patients responded. There was no clear evidence that CHAH increased likelihood of remaining at home during the final 2 weeks of life. However, the service was associated with fewer GP out of hours visits. All respondent groups rated CHAH favourably compared to standard care but emphasized different aspects. District nurses rated CHAH as better than standard care in terms of adequacy of night care and support for the carer, GPs in terms of anxiety and depression, and informal carers in terms of control of pain and nausea. Thus whilst CHAH was not found to increase the likelihood of remaining at home, at appeared to be associated with better quality home care.


Interoception and Empathy Impact Perspective Taking.
Adopting the perspective of another person is an important aspect of social cognition and has been shown to depend on multisensory signals from one's own body. Recent work suggests that interoceptive signals not only contribute to own-body perception and self-consciousness, but also to empathy. Here we investigated if social cognition - in particular adopting the perspective of another person - can be altered by a systematic manipulation of interoceptive cues and further, if this effect depends on empathic ability. The own-body transformation task (OBT) - wherein participants are instructed to imagine taking the perspective and position of a virtual body presented on a computer screen - offers an effective way to measure reaction time differences linked to the mental effort of taking an other's perspective. Here, we adapted the OBT with the flashing of a silhouette surrounding the virtual body, either synchronously or asynchronously with the timing of participants' heartbeats. We evaluated the impact of this cardio-visual synchrony on reaction times and accuracy rates in the OBT. Empathy was assessed with the empathy quotient (EQ) questionnaire. Based on previous work using the cardio-visual paradigm, we predicted that synchronous (vs. asynchronous) cardio-visual stimulation would increase self-identification with the virtual body and facilitate participants' ability to adopt the virtual body's perspective, thereby enhancing performance on the task, particularly in participants with higher empathy scores. We report that participants with high empathy showed significantly better performance during the OBT task during synchronous versus asynchronous cardio-visual stimulation. Moreover, we found a significant positive correlation between empathic ability and the synchrony effect (the difference in reaction times between the asynchronous and synchronous conditions). We conclude that synchronous cardio-visual stimulation between the participant's body and a virtual body during an OBT task makes it easier to adopt the virtual body's perspective, presumably based on multisensory integration processes. However, this effect depended on empathic ability, suggesting that empathy, interoception and social perspective taking are inherently linked.


Increased induction of apoptosis of human colorectal cancer cells after preoperative treatment with 5-fluorouracil.
We examined whether the administration of 5-fluorouracil (5-FU) could enhance apoptosis of colorectal cancer cells, and we investigated the relationship between apoptosis and the expression of Ki-67, p53, and c-myc. Twenty patients with advanced colorectal cancer were divided into two groups. Ten received continuous intravenous 5-FU at 500 mg/body/day for 7 days preoperatively and 10 did not receive 5-FU and served as controls. Apoptotic cells were stained by so-called TUNEL method (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling). Apoptosis of cancer cells increased significantly to 18+/-6% in the 5-FU-treated group as compared to the controls (3+/-1%; p<0.001). Expression of Ki-67, a indicator of cell proliferation, was inversely correlated with the TUNEL staining that was specific for apoptosis and the percentage of cells immunostained for Ki-67 fell significantly to 34+/-14% of the apoptotic area as compared to 72+/-12% in controls (p<0.001). There was no clear correlation between expression of apoptosis and the expression of p53 or c-myc.


The development of a model of community garden benefits to wellbeing.
Community gardens contribute to community wellbeing by influencing the nutritional and social environment. The aim of this research was to develop a model that communicates the many benefits of community garden participation as described in the academic literature, to a diverse audience of laypersons. This model is an example of effective knowledge translation because the information is able to be more than simply understood but also practically applied. From April to August 2015, a model depicting the many benefits of community garden participation was prepared based on a global, critical literature review. The wellbeing benefits from community garden participation have been grouped into factors influencing the nutritional health environment and factors influencing the social environment. The graphic chosen to form the basis of the model is a fractal tree of life. In October 2015, to test the models comprehension and to obtain stakeholder feedback this model was presented to a diverse group of community members, leaders and workers from the Tāmaki region of Auckland, New Zealand. The model we present here effectively and clearly translates knowledge obtained from the academic literature on the benefits to wellbeing from community garden participation into a tool that can be used, adapted and developed by community groups, government agencies and health promoters.


Gastric smooth muscle hamartoma in a cat.
An 11-year-old cat presented for evaluation of intermittent vomiting, constipation and hyporexia of 3 weeks duration. Ultrasonographic and endoscopic examination revealed a soft tissue mass adjacent to the lower gastro-esophageal sphincter. Surgical excision of the mass was successfully performed resulting in a resolution of clinical signs. Histologically the mass was consistent with a smooth muscle hamartoma. At follow-up 7 months after surgery, the cat remained free from clinical signs.


Aging with ING: a comparative study of different forms of stress induced premature senescence.
Cell senescence contributes to organismal aging and is induced by telomere erosion and an ensuing DNA damage signal as cells reach the end of their replicative lifespan in vitro or in vivo. Stresses induced by oncogene or tumor suppressor hyperactivation, oxidative stress, ionizing radiation and other DNA damaging agents result in forms of stress induced premature senescence (SIPS) that show similarities to replicative senescence. Since replicative senescence and SIPS occur over many days and many population doublings of the mass cultures of primary cells used to study senescence, the sequence of events that occur downstream of senescence signaling can be challenging to define. Here we compare a new model of ING1a-induced senescence with several other forms of senescence. The ING1a epigenetic regulator synchronously induces senescence in mass cultures several-fold faster than all other agents, taking 24 and 36 hours to activate the Rb/ p16INK4a, but not the p53 tumor suppressor axis to efficiently induce senescence. ING1a induces expression of intersectin 2, a scaffold protein necessary for endocytosis, altering the stoichiometry of endocytosis proteins, subsequently blocking growth factor uptake leading to activation of Rb signaling to block cell growth. ING1a acts as a novel link in the activation of the Rb pathway that can impose senescence in the absence of activating p53-mediated DNA damage signaling, and should prove useful in defining the molecular events contributing to Rb-induced senescence.


Do medical students require education on issues related to plagiarism?
In the course of our professional experience, we have seen that many medical students plagiarise. We hypothesised that they do so out of ignorance and that they require formal education on the subject. With this objective in mind, we conducted a teaching session on issues related to plagiarism. As a part of this, we administered a quiz to assess their baseline knowledge on plagiarism and a questionnaire to determine their attitudes towards it. We followed this up with an interactive teaching session, in which we discussed various aspects of plagiarism. We subjected the data obtained from the quiz and questionnaire to bivariate and multivariate analysis. A total of 423 medical students participated in the study. Their average score for the quiz was 4.96±1.67 (out of 10). Age, gender and years in medical school were not significantly associated with knowledge regarding plagiarism. The knowledge scores were negatively correlated with permissive attitudes towards plagiarism and positively correlated with attitudes critical of the practice. Men had significantly higher scores on permissive attitudes compared to women . In conclusion, we found that the medical students' knowledge regarding plagiarism was limited. Those with low knowledge scores tended to have permissive attitudes towards plagiarism and were less critical of the practice. We recommend the inclusion of formal instruction on this subject in the medical curriculum, so that this form of academic misconduct can be tackled.


Memory--a century of consolidation.
The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the time-dependent processes that create our lasting memories.


Accessing university education: perceptions, preferences, and expectations for interpreting by deaf students.
This paper provides a brief review of the history of deaf education in Australia, Australian Sign Language (Auslan), and Auslan interpreting. A panel of Australian deaf university students from diverse linguistic and educational backgrounds provides insights into their perceptions of sign language interpreting provision in university lectures. They commented on their interpreting preferences after viewing two videotaped segments of university lecture interpretation, one demonstrating a predominantly free approach and the other a predominantly literal approach. Expectations of the deaf students were explored in relation to the educational backgrounds and qualifications of university interpreters; comprehension of interpreters is also discussed. Results suggest that the university students preferred interpreters to combine both interpretation styles, switching between literal and free approaches when appropriate. In doing so, students can access lecture content in Auslan while accessing subject-specific terminology or academic language in English. In terms of qualifications, the students advocated for interpreters to have a university qualification in general, especially if they are working in a university context. However, the students also acknowledged that interpreting did not provide them with full access in educational settings.


Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.
Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.


Fertilization and blastoderm development of quail oocytes after intracytoplasmic injection of chicken sperm bearing the W chromosome.
Our previous study demonstrated that elongated spermatids and sperm carrying the female-specific W-chromosome of the sex-reversed domestic fowl can activate the mouse oocyte, but whether they can fertilize the avian oocyte and lead to a developing zygote remains undetermined. A single sperm isolated from the semen and testis of normal rooster and from a testis of sex-reversed hen was microinjected into a quail oocyte and cultured for 20 to 24 h. Blastoderms were fixed, cleaved, nuclei stained by 4',6'-diamidino-2-phenylin-dole, and developmental stages were assessed. In the normal rooster group, ejaculated and testicular sperm induced blastodermal development in 22.6 and 20% of the quail oocytes, respectively. The developmental stages ranged from IV to VII. In the sex-reversal group, 20% of injected testicular sperm induced blastodermal development. The blastodermal stages varied from stage III to VI. Blastoderms after 4',6'-diamidino-2-phenylindole staining were assayed by PCR to identify the W chromosome of either chicken sperm or quail oocyte. The PCR assay results showed that 2 out of 9 developed blastoderms microinjected with sperm of sex-reversed hen were identified containing the female-specific W chromosome derived from sex-reversed hen. From these results, it is concluded that chicken sperm bearing the W chromosome possess fertilizing ability and can function to stimulate blastoderm development similar to that of normal chicken sperm carrying the Z chromosome.


Similar local control between phenol- and ethanol-treated giant cell tumors of bone.
Giant cell tumors (GCTs) of bone often are treated with curettage, adjuvant therapy, and cementation. Phenol is a commonly used adjuvant associated with local control rates ranging from 9% to 25%. However, it is corrosive to the eyes, skin, and respiratory tract. Ethanol is readily available and does not cause chemical burns on contact, but it is unclear whether ethanol can achieve similar local control rates as phenol for treating GCTs. We evaluated (1) the recurrence rate and recurrence-free Kaplan-Meier survival function, (2) Musculoskeletal Tumor Society (MSTS) functional score (1993 version), and (3) complications of two groups of patients with GCTs treated with extensive curettage, local adjuvant therapy with phenol or ethanol, and cement reconstruction, to determine if ethanol was a reasonable alternative to phenol. We retrospectively reviewed all 26 patients with GCTs in the long bones of extremities treated with curettage, high-speed burring, phenolization, and cementation between May 1995 and November 2001, and 35 patients treated with the same protocol, except phenol was replaced with 95% ethanol, between November 2001 and November 2007. The recurrence rates, Kaplan-Meier recurrence-free survival curves, and MSTS functional scores of these two treatment groups were compared with Fisher's exact test, Tarone-Ware test, and Mann-Whitney U test, respectively. The minimum followup was 36 months (mean, 58 months; range, 36-156 months). Local recurrence rates were similar in the two groups: 11% in the ethanol group and 12% in the phenol group. The survival curves (using local recurrence as an endpoint) of the two groups were similar. The mean MSTS functional score was 27.3 (91%) for the ethanol group and 26.9 (90%) for the phenol group. Ethanol is a reasonable alternative to phenol when adjuvant therapy is considered in the treatment of GCTs of long bones. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Measurement of detector-corrected observables sensitive to the anomalous production of events with jets and large missing transverse momentum in p p collisions at s = 13 TeV using the ATLAS detector.
Observables sensitive to the anomalous production of events containing hadronic jets and missing momentum in the plane transverse to the proton beams at the Large Hadron Collider are presented. The observables are defined as a ratio of cross sections, for events containing jets and large missing transverse momentum to events containing jets and a pair of charged leptons from the decay of a Z / γ ∗ boson. This definition minimises experimental and theoretical systematic uncertainties in the measurements. This ratio is measured differentially with respect to a number of kinematic properties of the hadronic system in two phase-space regions; one inclusive single-jet region and one region sensitive to vector-boson-fusion topologies. The data are found to be in agreement with the Standard Model predictions and used to constrain a variety of theoretical models for dark-matter production, including simplified models, effective field theory models, and invisible decays of the Higgs boson. The measurements use 3.2 fb - 1 of proton-proton collision data recorded by the ATLAS experiment at a centre-of-mass energy of 13 TeV and are fully corrected for detector effects, meaning that the data can be used to constrain new-physics models beyond those shown in this paper.


Time course of platelet alpha granule release in acute myocardial infarction treated with streptokinase.
To determine the time course of platelet alpha granule release in patients with acute myocardial infarction treated with streptokinase. A prospective study. Coronary care unit. Nine with myocardial infarction treated with both streptokinase and aspirin, and nine with acute chest pain but without myocardial infarction, who were treated with aspirin only. All patients received 250 mg aspirin on admission and 150 mg once daily thereafter. All patients who fulfilled the indications for streptokinase received 1.5 megaunits, in a single infusion. After the initial medication, serial measurements of plasma beta thromboglobulin and plasma platelet factor 4 were performed at fixed intervals after the onset of chest pain. The primary endpoint sought was the peak value of beta thromboglobulin and platelet factor 4 in each individual. The median peak plasma beta thromboglobulin in the infarction group was substantially higher than in those without infarction, at 37 (range 12 to 210) v 15 (9 to 36) mg/litre, P < 0.01. The corresponding values for plasma platelet factor 4 were 4.6 (2.4 to 60.0) v 2.2 (< 2 to 8.5) mg/litre, P < 0.01. Increased values were seen only within the first 12 h after onset of chest pain, and after 12 h there was no difference between the patients with myocardial infarction and those without. Aspirin treatment did not abolish alpha granule release. In patients with acute myocardial infarction treated with streptokinase the content of the alpha granules is released within the first 12 h after the onset of chest pain. Aspirin apparently does not abolish this release.