Comparing the Effectiveness of Blood Flow Restriction and Traditional Heavy Load Resistance Training in the Post-Surgery Rehabilitation of Anterior Cruciate Ligament Reconstruction Patients: A UK National Health Service Randomised Controlled Trial.
We implemented a blood flow restriction resistance training (BFR-RT) intervention during an 8-week rehabilitation programme in anterior cruciate ligament reconstruction (ACLR) patients within a National Health Service setting. To compare the effectiveness of BFR-RT and standard-care traditional heavy-load resistance training (HL-RT) at improving skeletal muscle hypertrophy and strength, physical function, pain and effusion in ACLR patients following surgery. 28 patients scheduled for unilateral ACLR surgery with hamstring autograft were recruited for this parallel-group, two-arm, single-assessor blinded, randomised clinical trial following appropriate power analysis. Following surgery, a criteria-driven approach to rehabilitation was utilised and participants were block randomised to either HL-RT at 70% repetition maximum (1RM) (n = 14) or BFR-RT (n = 14) at 30% 1RM. Participants completed 8 weeks of biweekly unilateral leg press training on both limbs, totalling 16 sessions, alongside standard hospital rehabilitation. Resistance exercise protocols were designed consistent with standard recommended protocols for each type of exercise. Scaled maximal isotonic strength (10RM), muscle morphology of the vastus lateralis of the injured limb, self-reported function, Y-balance test performance and knee joint pain, effusion and range of motion (ROM) were assessed at pre-surgery, post-surgery, mid-training and post-training. Knee joint laxity and scaled maximal isokinetic knee extension and flexion strength at 60°/s, 150°/s and 300°/s were measured at pre-surgery and post-training. Four participants were lost, with 24 participants completing the study (12 per group). There were no adverse events or differences between groups for any baseline anthropometric variable or pre- to post-surgery change in any outcome measure. Scaled 10RM strength significantly increased in the injured limb (104 ± 30% and 106 ± 43%) and non-injured limb (33 ± 13% and 39 ± 17%) with BFR-RT and HL-RT, respectively, with no group differences. Significant increases in knee extension and flexion peak torque were observed at all speeds in the non-injured limb with no group differences. Significantly greater attenuation of knee extensor peak torque loss at 150°/s and 300°/s and knee flexor torque loss at all speeds was observed with BFR-RT. No group differences in knee extensor peak torque loss were found at 60°/s. Significant and comparable increases in muscle thickness (5.8 ± 0.2% and 6.7 ± 0.3%) and pennation angle (4.1 ± 0.3% and 3.4 ± 0.1%) were observed with BFR-RT and HL-RT, respectively, with no group differences. No significant changes in fascicle length were observed. Significantly greater and clinically important increases in several measures of self-reported function (50-218 ± 48% vs. 35-152 ± 56%), Y-balance performance (18-59 ± 22% vs. 18-33 ± 19%), ROM (78 ± 22% vs. 48 ± 13%) and reductions in knee joint pain (67 ± 15% vs. 39 ± 12%) and effusion (6 ± 2% vs. 2 ± 2%) were observed with BFR-RT compared to HL-RT, respectively. BFR-RT can improve skeletal muscle hypertrophy and strength to a similar extent to HL-RT with a greater reduction in knee joint pain and effusion, leading to greater overall improvements in physical function. Therefore, BFR-RT may be more appropriate for early rehabilitation in ACLR patient populations within the National Health Service.


Improved survival of gastric cancer with tumour Epstein-Barr virus positivity: an international pooled analysis.
About 9% of gastric carcinomas have Epstein-Barr virus (EBV) in the tumour cells, but it is unclear whether viral presence influences clinical progression. We therefore examined a large multicentre case series for the association of tumour EBV status with survival after gastric cancer diagnosis, accounting for surgical stage and other prognostic factors. We combined individual-level data on 4599 gastric cancer patients diagnosed between 1976 and 2010 from 13 studies in Asia (n=8), Europe (n=3), and Latin America (n=2). EBV positivity of tumours was assessed by in situ hybridisation. Mortality HRs for EBV positivity were estimated by Cox regression models stratified by study, adjusted for distributions of sex (71% male), age (mean 58 years), stage (52% tumour-node-metastasis stages III or IV), tumour histology (49% poorly differentiated, 57% Lauren intestinal-type), anatomic subsite (70% non-cardia) and year of diagnosis. Variations by study and continent were assessed using study-specific HRs for EBV positivity. During median 3.0 years follow-up, 49% of patients died. Stage was strongly predictive of mortality, with unadjusted HRs (vs stage I) of 3.1 for stage II, 8.1 for stage III and 13.2 for stage IV. Tumour EBV positivity was 8.2% overall and inversely associated with stage (adjusted OR: 0.79 per unit change). Adjusted for stage and other confounders, EBV positivity was associated with lower mortality (HR, 0.72; 95% CI 0.61 to 0.86), with low heterogeneity among the study populations (p=0.2). The association did not significantly vary across patient or tumour characteristics. There was no significant variation among the three continent-specific HRs (p=0.4). Our findings suggest that tumour EBV positivity is an additional prognostic indicator in gastric cancer. Further studies are warranted to identify the mechanisms underlying this protective association.


Designing paper-based records to improve the quality of nursing documentation in hospitals: A scoping review.
Inpatient nursing documentation facilitates multi-disciplinary team care and tracking of patient progress. In both high- and low- and middle-income settings, it is largely paper-based and may be used as a template for electronic medical records. However, there is limited evidence on how they have been developed. To synthesise evidence on how paper-based nursing records have been developed and implemented in inpatient settings to support documentation of nursing care. A scoping review guided by the Arksey and O'Malley framework and reported using PRISMA-ScR guidelines. We included studies that described the process of designing paper-based inpatient records and excluded those focussing on electronic records. Included studies were published in English up to October 2019. PubMed, CINAHL, Web of Science and Cochrane supplemented by free-text searches on Google Scholar and snowballing the reference sections of included papers. 12 studies met the eligibility criteria. We extracted data on study characteristics, the development process and outcomes related to documentation of inpatient care. Studies reviewed followed a process of problem identification, literature review, chart (re)design, piloting, implementation and evaluation but varied in their execution of each step. All studies except one reported a positive change in inpatient documentation or the adoption of charts amid various challenges. The approaches used seemed to work for each of the studies but could be strengthened by following a systematic process. Human-centred Design provides a clear process that prioritises the healthcare professional's needs and their context to deliver a usable product. Problems with the chart could be addressed during the design phase rather than during implementation, thereby promoting chart ownership and uptake since users are involved throughout the design. This will translate to better documentation of inpatient care thus facilitating better patient tracking, improved team communication and better patient outcomes. Paper-based charts should be designed in a systematic and clear process that considers patient's and healthcare professional's needs contributing to improved uptake of charts and therefore better documentation.


Molecular specificity of multiple hippocampal processes governing fear extinction.
Over many years, fear extinction has been conceptualized as one dominant process, new inhibitory learning, which serves to dampen previously acquired fear. Here we present an alternative view, that brain region-specific processing of representations, expectations and emotional attributes of the fear-provoking event, recruits unique mechanisms that interdependently contribute to the conditioning and extinction of fear. The co-occurrence of these mechanisms within the fear circuit can thus be tracked and differentiated at a molecular and cellular level. Among others, the transcriptional regulators cFos, cAMP-dependent response element binding protein (CREB), Zif268, and extracellular signal-regulated kinases (Erk) stand out as hippocampal nuclear markers signaling novelty, arousal, retrieval, and prediction error, respectively. Consistent with evidence from human studies, these findings indicate that, beyond inhibitory learning, fear extinction requires modification of the emotional attributes and expectations that define the threatening context. Given the likely dysregulation of one or more of these processes in anxiety disorders, a key research challenge for the future is the identification and enhancement of individual extinction mechanisms to target the specific components of fear. Environmental stimuli lacking affective properties (conditioned stimuli, CS) rapidly become threatening if presented with stressful events (unconditioned stimuli, US). Consequently, based on a CS-US association, the presentation of the CS triggers species-specific fear responses until the US consistently stops occurring. At that point, new learning takes place and the fear response declines, a phenomenon termed extinction. The view that extinction occurs because a new, inhibitory CS-noUS association gains control over behavior, has remained dominant in the field. The implications of impaired fear regulation in the development of anxiety disorders have stimulated intense research in this area. Rodent studies identified the circuits involved in the conditioning and extinction of fear of salient cues, generating data that were confirmed in humans with brain imaging approaches. Nevertheless, research with experimental animals has not fully taken advantage of human data in order to better interpret extinction mechanisms in the framework of learning, expectation and emotion governing fear-motivated behavior. The present article aims to summarize recent molecular evidence on fear extinction, focusing on hippocampal mechanisms and experimental models of contextual fear, and compare the results with other relevant fear paradigms and human imaging studies. Instead of conceptualizing extinction learning as one process, such as CS-noUS association or inhibitory learning, we propose that fear extinction reflects the behavioral output of several region-specific learning processes that modify different components of the conditioning memory. The significance of these findings is discussed in the framework of fear regulation and anxiety disorders.


Phase III randomized study of second line ADI-PEG 20 plus best supportive care versus placebo plus best supportive care in patients with advanced hepatocellular carcinoma.
Arginine depletion is a putative target in hepatocellular carcinoma (HCC). HCC often lacks argininosuccinate synthetase, a citrulline to arginine-repleting enzyme. ADI-PEG 20 is a cloned arginine degrading enzyme-arginine deiminase-conjugated with polyethylene glycol. The goal of this study was to evaluate this agent as a potential novel therapeutic for HCC after first line systemic therapy. Patients with histologically proven advanced HCC and Child-Pugh up to B7 with prior systemic therapy, were randomized 2 : 1 to ADI-PEG 20 18 mg/m2 versus placebo intramuscular injection weekly. The primary end point was overall survival (OS), with 93% power to detect a 4-5.6 months increase in median OS (one-sided α = 0.025). Secondary end points included progression-free survival, safety, and arginine correlatives. A total of 635 patients were enrolled: median age 61, 82% male, 60% Asian, 52% hepatitis B, 26% hepatitis C, 76% stage IV, 91% Child-Pugh A, 70% progressed on sorafenib and 16% were intolerant. Median OS was 7.8 months for ADI-PEG 20 versus 7.4 for placebo (P = 0.88, HR = 1.02) and median progression-free survival 2.6 months versus 2.6 (P = 0.07, HR = 1.17). Grade 3 fatigue and decreased appetite occurred in <5% of patients. Two patients on ADI-PEG 20 had ≥grade 3 anaphylactic reaction. Death rate within 30 days of end of treatment was 15.2% on ADI-PEG 20 versus 10.4% on placebo, none related to therapy. Post hoc analyses of arginine assessment at 4, 8, 12 and 16 weeks, demonstrated a trend of improved OS for those with more prolonged arginine depletion. ADI-PEG 20 monotherapy did not demonstrate an OS benefit in second line setting for HCC. It was well tolerated. Strategies to enhance prolonged arginine depletion and synergize the effect of ADI-PEG 20 are underway. www.clinicaltrials.gov (NCT 01287585).


Biomechanical comparison of the holding strength of a peek-optima circular plate versus a stainless steel oblique T-plate for radioscapholunate arthrodesis.
Radioscapholunate arthrodesis is an accepted treatment for posttraumatic radiocarpal arthritis that preserves some wrist motion. Good results are dependent on secure fixation while avoiding hardware-related side effects. A small radiolucent countersunk circular plate placed over the radiocarpal joint may offer a low-profile technique for achieving secure fixation of the radioscapholunate joint. The purpose of this study was to compare the biomechanical performance of this circular plate, when applied in this manner, to that of a more conventional fixation technique such as a 3.5-mm T-plate. Ten pairs of fresh-frozen cadaveric wrists were amputated 7 cm proximal to the radiocarpal joint. One wrist from each pair was fixed with a T-plate (DePuy, Inc., Warsaw, IN), and the contralateral wrist was fixed with a circular plate (Xpode plate; TriMed, Inc., Valencia, CA). The radius and scaphoid-lunate complex were each rigidly held and mounted into a materials testing machine. Translational forces to mimic extension and flexion movements were applied cyclically for 40 cycles, followed by failure testing in extension. Cyclic tests revealed no statistically significant differences between the 2 fixation plates although resistance to flexion motion was higher than resistance to extension motion. The average load at failure was no different between the T-plate and circular plate. However, a ratio of the failure loads (T-plate to circular plate) demonstrated a 58% higher load for the circular plate. A countersunk circular plate provides similar biomechanical performance to the T-plate for radioscapholunate arthrodesis.


Does extending health insurance coverage to the uninsured improve population health outcomes?
An ongoing debate exists about whether the US should adopt a universal health insurance programme. Much of the debate has focused on programme implementation and cost, with relatively little attention to benefits for social welfare. To estimate the effect on US population health outcomes, measured by mortality, of extending private health insurance to the uninsured, and to obtain a rough estimate of the aggregate economic benefits of extending insurance coverage to the uninsured. We use state-level panel data for all 50 states for the period 1990-2000 to estimate a health insurance augmented, aggregate health production function for the US. An instrumental variables fixed-effects estimator is used to account for confounding variables and reverse causation from health status to insurance coverage. Several observed factors, such as income, education, unemployment, cigarette and alcohol consumption and population demographic characteristics are included to control for potential confounding variables that vary across both states and time. The results indicate a negative relationship between private insurance and mortality, thus suggesting that extending insurance to the uninsured population would result in an improvement in population health outcomes. The estimate of the marginal effect of insurance coverage indicates that a 10% increase in the population-insured rate of a state reduces mortality by 1.69-1.92%. Using data for the year 2003, we calculate that extending private insurance coverage to the entire uninsured population in the US would save over 75 000 lives annually and may yield annual net benefits to the nation in excess of $US400 billion. This analysis suggests that extending health insurance coverage through the private market to the 46 million Americans without health insurance may well produce large social economic benefits for the nation as a whole.


Population-specific genetic modification of Huntington's disease in Venezuela.
Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin but not explaining the earlier age at onset in these Venezuelans. GWA analysis of the Venezuelan HD cluster suggests both population-specific and population-shared genetic modifiers. Genome-wide significant signals at 7p21.2-21.1 and suggestive association signals at 4p14 and 17q21.2 are evident only in Venezuelan HD, but genome-wide significant association signals at the established European chromosome 15 modifier locus are improved when Venezuelan HD data are included in the meta-analysis. Venezuelan-specific association signals on chromosome 7 center on SOSTDC1, which encodes a bone morphogenetic protein antagonist. The corresponding SNPs are associated with reduced expression of SOSTDC1 in non-Venezuelan tissue samples, suggesting that interaction of reduced SOSTDC1 expression with a population-specific genetic or environmental factor may be responsible for modification of HD onset in Venezuela. Detection of population-specific modification in Venezuelan HD supports the value of distinct disease populations in revealing novel aspects of a disease and population-relevant therapeutic strategies.


A simple, inexpensive device for nucleic acid amplification without electricity-toward instrument-free molecular diagnostics in low-resource settings.
Molecular assays targeted to nucleic acid (NA) markers are becoming increasingly important to medical diagnostics. However, these are typically confined to wealthy, developed countries; or, to the national reference laboratories of developing-world countries. There are many infectious diseases that are endemic in low-resource settings (LRS) where the lack of simple, instrument-free, NA diagnostic tests is a critical barrier to timely treatment. One of the primary barriers to the practicality and availability of NA assays in LRS has been the complexity and power requirements of polymerase chain reaction (PCR) instrumentation (another is sample preparation). In this article, we investigate the hypothesis that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays. We assess the heater's equivalence to commercially available PCR instruments through the characterization of the temperature profiles produced, and a minimal method comparison. Versions of the prototype for several different isothermal techniques are presented. We demonstrate that an electricity-free heater based on exothermic chemical reactions and engineered phase change materials can successfully incubate isothermal NA amplification assays, and that the results of those assays are not significantly different from ones incubated in parallel in commercially available PCR instruments. These results clearly suggest the potential of the non-instrumented nucleic acid amplification (NINA) heater for molecular diagnostics in LRS. When combined with other innovations in development that eliminate power requirements for sample preparation, cold reagent storage, and readout, the NINA heater will comprise part of a kit that should enable electricity-free NA testing for many important analytes.


Identification and climatology of cut-off lows near the tropopause.
Cut-off low pressure systems (COLs) are defined as closed lows in the upper troposphere that have become completely detached from the main westerly current. These slow-moving systems often affect the weather conditions at the earth's surface and also work as a mechanism of mass transfer between the stratosphere and the troposphere, playing a significant role in the net flow of tropospheric ozone. In the first part of this work we provide a comprehensive summary of results obtained in previous studies of COLs. Following this, we present three long-term climatologies of COLs. The first two climatologies are based on the conceptual model of a COL, using European Centre for Medium-range Weather Forecasts (ECMWF) analyses (1958-2002) and National Centers for Environmental Prediction-National Center for Atmospheric Research (1948-2006) reanalysis data sets. The third climatology uses a different method of detection, which is based on using potential vorticity as the physical parameter of diagnosis. This approach was applied only to the ECMWF reanalysis data. The final part of the paper is devoted to comparing results obtained by these different climatologies in terms of areas of preferential occurrence, life span, and seasonal cycle. Despite some key differences, the three climatologies agree in terms of the main areas of COL occurrence, namely (1) southwestern Europe, (2) the eastern north Pacific coast, and (3) the north China-Siberian region. However, it is also shown that the detection of these areas of main COL occurrence, as obtained using the potential vorticity approach, depends on the level of isentropic analysis used.


A genome-wide association study identifies protein quantitative trait loci (pQTLs).
There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8x10(-57)), CCL4L1 (p = 3.9x10(-21)), IL18 (p = 6.8x10(-13)), LPA (p = 4.4x10(-10)), GGT1 (p = 1.5x10(-7)), SHBG (p = 3.1x10(-7)), CRP (p = 6.4x10(-6)) and IL1RN (p = 7.3x10(-6)) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8x10(-40)), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways.


Wild waterfowl migration and domestic duck density shape the epidemiology of highly pathogenic H5N8 influenza in the Republic of Korea.
Highly pathogenic avian influenza (HPAI) viruses threaten human and animal health yet their emergence is poorly understood, partly because sampling of the HPAI Asian-origin H5N1 lineage immediately after its identification in 1996 was comparatively sparse. The discovery of a novel H5N8 virus in 2013 provides a new opportunity to investigate HPAI emergence in greater detail. Here we investigate the origin and transmission of H5N8 in the Republic of Korea, the second country to report the new strain. We reconstruct viral spread using phylogeographic methods and interpret the results in the context of ecological data on poultry density, overwintering wild bird numbers, and bird migration patterns. Our results indicate that wild waterfowl migration and domestic duck density were important to H5N8 epidemiology. Specifically, we infer that H5N8 entered the Republic of Korea via Jeonbuk province, then spread rapidly among western provinces where densities of overwintering waterfowl and domestic ducks are higher, yet rarely persisted in eastern regions. The common ancestor of H5N8 in the Republic of Korea was estimated to have arrived during the peak of inward migration of overwintering birds. Recent virus isolations likely represent re-introductions via bird migration from an as-yet unsampled reservoir. Based on the limited data from outside the Republic of Korea, our data suggest that H5N8 may have entered Europe at least twice, and Asia at least three times from this reservoir, most likely carried by wild migrating birds.


Effect of preovulatory progesterone elevation and duration of progesterone elevation on the pregnancy rate of frozen-thawed embryo transfer in natural cycles.
To assess the incidence of P elevation (PE) in natural cycles and evaluate its effect on frozen-thawed embryo transfer cycles performed in natural cycles (FET-NC). Retrospective analysis. A tertiary assisted reproductive unit. Subfertile woman who did not conceive in their stimulated IVF cycle and underwent the first FET-NC cycle. Achieved serum samples were assayed for P concentrations from the day of LH surge up to 3 days before the surge. The cutoff level of PE was defined as 5 nmol/L. Clinical and ongoing pregnancy rates. The incidence of PE in natural cycles was 173 of 610 (28.4%). There were no significant differences in both clinical and ongoing pregnancy rates (39.0% vs. 37.3% and 32.5% vs. 31.7%) between those with vs. without PE on the day of LH surge. If PE lasted for 2 days or more, there was a significant reduction in the clinical pregnancy rate (39.4% vs. 20.7%). Using multivariate logistic regression, women's age, PE for 2 days or more, and the number of top-quality embryos were the significant factors for clinical pregnancy rates in FET-NC. The incidence of PE in FET-NC was similar to that in stimulated cycles. Progesterone elevation for 2 days or more before the LH surge impaired the clinical pregnancy rate of FET-NC, whereas PE on the day of LH surge only did not have such an adverse effect.


Sleep, synaptic connectivity, and hippocampal memory during early development.
Sleep, specifically sleep slow-wave activity (SWA), contributes to global synaptic homeostasis in neocortical networks by downscaling synaptic connections that were potentiated during prior wakefulness. In parallel, SWA supports the consolidation of hippocampus-dependent episodic memory, a process linked to local increases in synaptic connectivity. During development, both SWA and episodic memory show parallel time courses: distinct SWA and capabilities to form episodic memory become established during infancy and then profoundly increase across childhood until puberty. We propose that the parallel increases across childhood reflect an imbalance in the underlying regulation of synaptic connectivity during sleep; although memory consolidation favoring synaptic potentiation is enhanced, global synaptic downscaling during sleep SWA does not attain complete recovery of homeostatic baseline levels.


Expression of subunits for the cAMP-sensitive 'olfactory' cyclic nucleotide-gated ion channel in the cochlea: implications for signal transduction.
Cyclic nucleotide-gated (CNG) ion channels have been implicated as functioning in sensory transduction and in second-messenger modulation of synaptic neurotransmitter release. The olfactory, cAMP-sensitive CNG ion channel in vivo is considered to comprise the pore-forming CNG2 subunit together with CNG5 and CNG4.3 modulatory subunits. The expression of these 'olfactory' CNG subunit transcripts in microdissected subfractions of the rat cochlea and hair cell libraries has been investigated with RT-PCR. Unmodified transcripts of CNG2 were detected in the organ of Corti, lateral wall and spiral ganglion subfractions. CNG5 message was found in both the sensory organ of Corti and the non-sensory lateral wall subfractions but not in the spiral ganglion subfraction. The CNG5 sequence obtained for the organ of Corti fraction encompassed 78% of the olfactory CNG5 cDNA sequence. CNG5 message has also been detected in an inner hair cell cDNA library. In the lateral wall, unmodified CNG5 sequence was observed as well as truncated versions of CNG5 transcripts, one of which was also found in the rat brain. The truncated versions were characterized by deletions that resulted in a shift in reading frame and the premature appearance of a stop codon. The 'olfactory' CNG4.3 cDNA was amplified from all three subfractions. Within the cochlea, CNG2 immunoreactivity was selectively distributed in a pattern similar to that of adenylyl cyclase type I. Immunoreactivity to CNG2 has been localized to stereocilia of inner hair cells. CNG5 immunoreactivity was associated with stereocilia and lateral plasma membranes of outer hair cells. We conclude that transcripts necessary for a functional cAMP-sensitive CNG ion channel are present in the cochlea resulting from combinations of CNG2 with CNG5 and CNG4.3. Further, the localization of CNG2 and CNG5 immunoreactivity to hair cell stereocilia suggests a role for cAMP-sensitive CNG channels in hair cell signal transduction.


In vivo hemodynamic characteristics of porcine stentless aortic valves.
The objective of this study was to elucidate the relationship of aortic pressure gradient (mPG) and effective orifice area (EOA) with mean systolic flow rate of left ventricle in patients who received a stentless aortic valve. Two hundred thirteen patients (age: 73 +/- 6 years, 123 men and 90 women) who received a Freestyle stentless valve in subcoronary position for aortic valve diseases were studied. EOA, mPG, and systolic aortic flow rate were determined by Doppler echocardiography at 1 and 20 months after implant. With follow-up, there was a 13% increase in EOA and a 30% decrease in mPG, both P <.01. Although systolic aortic flow did not change, the intercept of EOA-flow relationship increased significantly at late follow-up (0.56 +/- 0.13 v 0.11 +/- 0.13, P <.01). Multiple regression analysis showed that systolic aortic flow accounted for 54%, and mPG for only 27%, variation of EOA. Linear relationship between EOA and systolic aortic flow provides a comprehensive approach to describe stentless valve performance, when mean valve pressure gradient appears to be flow independent. These hemodynamic features distinguish stentless valves from stented or mechanical prosthesis. Ultimately, the variations in aortic root anatomy, surgical experience and their interactions are likely to become major determinants of in vivo performance of stentless aortic valves.


Science and law. When should judges admit or compel genetic tests?
During the past two decades, the use of DNA tests has revolutionized court proceedings in criminal and paternity cases. On the horizon is a new challenge for judges--whether to admit or compel genetic tests to confirm or predict genetic diseases and conditions in many more judicial contexts, e.g., decisions regarding culpability, sentencing, liability, causation, and damages. This Policy Forum reports on an empirical study of how judges would analyze these issues. The authors discuss the challenges these types of cases will bring to the court-room and suggest a series of questions that judges should consider in evaluating the need for genetic information in legal cases.


Immunohistochemical testing of BRAF V600E status in 1,120 tumor tissue samples of patients with brain metastases.
Brain metastases (BM) are frequent and carry a dismal prognosis. BRAF V600E mutations are found in a broad range of tumor types and specific inhibitors targeting BRAF V600E protein exist. We analyzed tumoral BRAF V600E-mutant protein expression using the novel mutation-specific antibody VE1 in a series of 1,120 tumor specimens (885 BM, 157 primary tumors, 78 extra-cranial metastases) of 874 BM patients. In 85 cases, we performed validation of immunohistochemical results by BRAF exon 15 gene sequencing. BRAF V600E protein was expressed in BM of 42/76 (55.3%) melanomas, 1/15 (6.7%) ovarian cancers, 4/72 (5.5%) colorectal cancers, 1/355 (0.3%) lung cancers, 2/6 thyroid cancers and 1/2 choriocarcinomas. BRAF V600E expression showed high intra-tumoral homogeneity and was similar in different tumor manifestations of individual patients. VE1 immunohistochemistry and BRAF exon 15 sequencing were congruent in 68/70 (97.1%) cases, but VE1 immunostaining identified small BRAF V600E expressing tumor cell aggregates in 10 cases with inconclusive genetic results. Melanoma patients with BRAF V600E mutant protein expressing tumors were significantly younger at diagnosis of the primary tumor and at operation of BM than patients with non-mutated tumors. In conclusion, expression of BRAF V600E mutant protein occurs in approximately 6% of BM and is consistent in different tumor manifestations of the same patient. Thus, BRAF V600E inhibiting therapies seem feasible in selected BM patients. Immunohistochemical visualization of V600E-mutant BRAF protein is a promising tool for patient stratification. An integrated approach combining both, VE1 immunohistochemistry and genetic analysis may increase the diagnostic accuracy of BRAF mutation analysis.


Phylogenetic evidence for host switching in the evolution of hantaviruses carried by Apodemus mice.
Phylogenetic analysis of three hantaviruses: Hantaan (HTNV), Dobrava (DOBV), and the newly designated serotype/genotype Saaremaa (SAAV) and their respective hosts, rodents of genus Apodemus, reveals a discrepancy in the virus-host relationships. While all Apodemus agrarius sequences from Europe and the Far East are monophyletic, SAAV (carried by the western subspecies of A. agrarius) shared the most recent ancestor with A. flavicollis-associated DOBV virus, but not with HTNV (carried by the eastern subspecies of A. agrarius). This suggests that host switching occurred in the evolution of these hantaviruses. A likely scenario includes transmission of ancestral DOBV to the western form of A. agrarius resulting in the ecological and reproductive isolation of ancestral SAAV. Approximate time-point of the hypothetical host switching estimated from maximum likelihood (ML) phylogenetic tree, 2.7-4.0 millions years ago (MYA), is closer to the present than the expected time of split between the two Apodemus species (not later than 6.5 MYA). Taken together with other proposed cases of host switching, our observations suggest that these events might not be exceptional in the hantavirus evolution.


Team performance in resuscitation teams: comparison and critique of two recently developed scoring tools.
Following high profile errors resulting in patient harm and attracting negative publicity, the healthcare sector has begun to focus on training non-technical teamworking skills as one way of reducing the rate of adverse events. Within the area of resuscitation, two tools have been developed recently aiming to assess these skills - TEAM and OSCAR. The aims of the study reported here were: The study consisted of two phases - reliability assessment; and content comparison, and correlation. Assessments were made by two resuscitation experts, who watched 24 pre-recorded resuscitation simulations, and independently rated team behaviours using both tools. The tools were critically appraised, and correlation between overall score surrogates was assessed. Both OSCAR and TEAM achieved high levels of inter-rater reliability (in the form of adequate intra-class coefficients) and minor significant differences between Wilcoxon tests. Comparison of the scores from both tools demonstrated a high degree of correlation (and hence concurrent validity). Finally, critique of each tool highlighted differences in length and complexity. Both OSCAR and TEAM can be used to assess resuscitation teams in a simulated environment, with the tools correlating well with one another. We envisage a role for both tools - with TEAM giving a quick, global assessment of the team, but OSCAR enabling more detailed breakdown of the assessment, facilitating feedback, and identifying areas of weakness for future training.


Organisational justice protects against the negative effect of workplace violence on teachers' sleep: a longitudinal cohort study.
This study aimed to examine the longitudinal association of workplace violence with disturbed sleep and the moderating role of organisational justice (ie, the extent to which employees are treated with fairness) in teaching. We identified 4988 teachers participating in the Finnish Public Sector study who reported encountering violence at work. Disturbed sleep was measured in three waves with 2-year intervals: the wave preceding exposure to violence, the wave of exposure and the wave following the exposure. Data on procedural and interactional justice were obtained from the wave of exposure to violence. The associations were examined using repeated measures log-binomial regression analysis with the generalised estimating equations method, adjusting for gender and age. Exposure to violence was associated with an increase in disturbed sleep (RR 1.32 (95% CI 1.15 to 1.52)) that also persisted after the exposure (RR 1.26 (95% CI 1.07 to 1.48)). The increase was higher among teachers perceiving the managerial practices as relatively unfair (RR 1.46 (95% CI 1.01 to 2.09) and RR 1.59 (95% CI 1.04 to 2.42) for interactional and procedural justice, respectively). By contrast, working in high-justice conditions seemed to protect teachers from the negative effect of violence on sleep. Our findings show an increase in sleep disturbances due to exposure to workplace violence in teaching. However, the extent to which teachers are treated with justice moderates this association. Although preventive measures for violence should be prioritised, resources aimed at promoting justice at schools can mitigate sleep problems associated with workplace violence.


Feasibility of soil dust source apportionment by the pyrolysis-gas chromatography/mass spectrometry method.
This study tested the feasibility of using pyrolysis (Py)-gas chromatography (GC)/mass spectrometry (MS) to obtain organic chemical species data suitable for source apportionment modeling of soil-derived coarse particulate matter (PM10) dust on ambient filters. A laboratory resuspension apparatus was used with known soils to generate simulated receptor filter samples loaded with approximately 0.4 mg of PM10 dust, which is within the range of mass loading on ambient filters. Py-GC/MS at 740 degrees C generated five times more resolvable compounds than were obtained with thermal desorption GC/MS at 315 degrees C. The identified compounds were consistent with literature from Py experiments using larger samples of bulk soils. A subset of 91 organic species out of the 178 identified Py products was used as input to CMB8 software in a demonstration of source apportionment using laboratory-generated mixtures simulating ambient filter samples. The 178 quantified organic species obtained by Py of soil samples is an improvement compared with the 38 organic species obtained by thermal desorption of soils and the four functionally defined organic fractions reported by thermal/ optical reflectance. Significant differences in the concentration of specific species were seen between samples from different sites, both geographically distant and close, using analysis of variance and cluster analysis. This feasibility study showed that Py-GC/MS can generate useful source profile data for receptor modeling and justifies continued method development.


Acute neural effects of fluoxetine on emotional regulation in depressed adolescents.
Adolescent major depressive disorder (MDD) is associated with disrupted processing of emotional stimuli and difficulties in cognitive reappraisal. Little is known however about how current pharmacotherapies act to modulate the neural mechanisms underlying these key processes. The current study therefore investigated the neural effects of fluoxetine on emotional reactivity and cognitive reappraisal in adolescent depression. Thirty-one adolescents with MDD were randomised to acute fluoxetine (10 mg) or placebo. Seventeen healthy adolescents were also recruited but did not receive any treatment for ethical reasons. During functional magnetic resonance imaging (fMRI), participants viewed aversive images and were asked to either experience naturally the emotional state elicited ('Maintain') or to reinterpret the content of the pictures to reduce negative affect ('Reappraise'). Significant activations were identified using whole-brain analysis. No significant group differences were seen when comparing Reappraise and Maintain conditions. However, when compared to healthy controls, depressed adolescents on placebo showed reduced visual activation to aversive pictures irrespective of the condition. The depressed adolescent group on fluoxetine showed the opposite pattern, i.e. increased visuo-cerebellar activity in response to aversive pictures, when compared to depressed adolescents on placebo. These data suggest that depression in adolescence may be associated with reduced visual processing of aversive imagery and that fluoxetine may act to reduce avoidance of such cues. This could reflect a key mechanism whereby depressed adolescents engage with negative cues previously avoided. Future research combining fMRI with eye-tracking is nonetheless needed to further clarify these effects.


Performance benefits of depression: sequential decision making in a healthy sample and a clinically depressed sample.
Previous research reported conflicting results concerning the influence of depression on cognitive task performance. Whereas some studies reported that depression enhances performance, other studies reported negative or null effects. These discrepant findings appear to result from task variation, as well as the severity and treatment status of participant depression. To better understand these moderating factors, we study the performance of individuals-in a complex sequential decision task similar to the secretary problem-who are nondepressed, depressed, and recovering from a major depressive episode. We find that depressed individuals perform better than do nondepressed individuals. Formal modeling of participants' decision strategies suggested that acutely depressed participants had higher thresholds for accepting options and made better choices than either healthy participants or those recovering from depression.


A prospective study of dietary fat and risk of prostate cancer.
The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis. We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer. We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51529 U.S. men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates. Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04-3.07, for high versus low quintile of intake; P [trend] = .06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95-2.78; P [trend] = .08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21-5.77; P = .02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and alpha-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with alpha-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and alpha-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67-7.04; P [trend] = .002). The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer. These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored.


Prescription opioid abuse in prison settings: A systematic review of prevalence, practice and treatment responses.
To systematically review the quantitative and qualitative evidence base pertaining to the prevalence, practice of, and treatment response to the diversion of prescribed opiates in the prison setting. Medline, Embase, CINAHL, PsycINFO, Google Scholar, ASSIA and Science Direct databases were searched for papers from 1995 to the present relevant to the abuse of prescribed opiate medication. Identified journals and their reference lists were hand searched for other relevant articles. Of the abstracts identified as relevant, full text papers were retrieved and critiqued against the inclusion criteria for the review. Three hundred and fifty-five abstracts were identified, leading to 42 full-text articles being retrieved. Of those, 10 papers were included in the review. Significant differences in abuse behaviours between different countries were reported. However, a key theme emerged from the data regarding a culture of nasal administration of prescribed sublingual buprenorphine within some prisons due to both reduced prevalence of injection within prison and reduced supplies of illicit drugs within prison. The buprenorphine/naloxone preparation appears to be less amenable to abuse. The review highlighted a paucity of empirical research pertaining to both prevalence of the phenomenon and treatment responses. Healthcare providers within prisons need to prescribe opioids in the least abuseable preparation since the risk of abuse is significant, despite widespread processes of supervised dispensing. Prescription medication abuse is not limited to opioids and the predominant drug of abuse in an individual prison can rapidly change according to availability.


Influenza-like illness outbreaks in nursing homes in Corsica, France, 2014-2015: epidemiological and molecular characterization.
To study the molecular epidemiology of the influenza outbreaks in nursing homes (NHs) to determine whether multiple influenza strains were involved. From September to December 2014, NHs in Corsica were invited to participate in an ongoing daily epidemiological and microbiological surveillance for influenza-like illness (ILI) among residents and health care workers (HCWs). The study involved 12 NHs. Respiratory illness meeting the ILI case definition was observed among 44 residents from whom 22 specimens were collected. Of the 22 residents with a nasopharyngeal sample, 13 (59 %) were positive for at least one of the 11 pathogens analysed. Among these 13 patients, 11 (92 %) presented a confirmed influenza (A/H3N2) and two had another respiratory virus: one human metapneumovirus and one human coronavirus. Of patients with a confirmed influenza A(H3N2), 10 (91 %) were vaccinated against influenza during the 2014-2015 season. Two influenza outbreaks were reported in two NHs, caused by influenza A(H3N2) strains belonging to cluster 3C.3 and 3C.2a. Although antivirals were available, prophylaxis was not used. Phylogenetic analysis seems to suggest no multiple introduction into the two NHs reporting the two influenza A(H3N2) outbreaks. A number of factors could have contributed to transmitting influenza in NHs including, the absence of administration of antiviral treatment for prophylaxis of all residents/staff regardless of immunization status because of the poor vaccine match during each outbreak, the intensive contacts with incompletely protected residents and HCWs, and the low adherence of NHs to notification of ILI outbreaks to the health authorities.


In vitro and in vivo activities of clinafloxacin, CI-990 (PD 131112), and PD 138312 versus enterococci.
Certain new fluoroquinolones have high activity against enterococci. Against Enterococcus faecalis (n = 18), MICs at which 90% of the isolates were inhibited were as follows (in micrograms per milliliter): clinafloxacin, 0.125; CI-990, 0.5; and PD 138312, 0.25 (compared with 1 microgram/ml for ciprofloxacin and 2 micrograms/ml for ofloxacin). Strains producing beta-lactamase or that were vancomycin resistant or resistant to high-level gentamicin were not quinolone cross-resistant. The drugs were bactericidal and were unaffected by 50% human serum. Oral efficacies (in milligrams per kilogram of body weight for 50% protective doses) in lethal mouse infections with quinolone-susceptible strains were 4.3 to 24 for clinafloxacin, 7.2 to 39 for CI-990, 7.2 to 76 for PD 138312, and 41 to > 100 for ciprofloxacin; when the drugs were given subcutaneously, the order was similar and values ranged from 1.1 to 12.5. Clinafloxacin, CI-990, and PD 138312 may have therapeutic potential in systemic enterococcal infections in humans.


Bilateral Central Retinal Vein Occlusion in a 40-Year-Old Man with Severe Coronavirus Disease 2019 (COVID-19) Pneumonia.
BACKGROUND COVID-19 is the disease caused by the novel virus, severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). The spectrum of disease seen in patients with COVID-19 infection ranges from asymptomatic or mild symptoms to severe pneumonia and even acute respiratory distress syndrome, which often requires invasive ventilation and intensive care. COVID-19-associated infection can be catastrophic, leading to both arterial and venous occlusion, microinfarcts, and multiorgan failure, although retinal vein occlusion has not yet been reported. CASE REPORT We present the case of a 40-year-old man who presented with a 3-day history of shortness of breath, cough, and fever. He also reported right calf pain and blurring of vision in both eyes. His medical history included hypertension and morbid obesity. The patient was found to have severe COVID-19 pneumonia on high-resolution computed tomography of the chest, right leg deep venous thrombosis on Doppler ultrasonography, and bilateral central retinal vein occlusion (RVO) on fundal examination. He was started on full-dose anticoagulation and discharged on rivaroxaban for 3 months. After 2 weeks of therapy, he had fully recovered from his COVID-19 symptoms and had near-normal vision. CONCLUSIONS COVID-19 infection can cause RVO. Early full-dose anticoagulation should be considered in high-risk patients with severe COVID-19 infection. Ophthalmologists and other clinicians should have a high index of suspicion for RVO in patients with COVID-19 infection who presenting with blurred vision and severe pneumonia.


Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs.
A simple synthetic route for the preparation of functional nanoscale graphene oxide (NGO), a novel nanocarrier for the loading and targeted delivery of anticancer drugs, is reported. The NGO is functionalized with sulfonic acid groups, which render it stable in physiological solution, followed by covalent binding of folic acid (FA) molecules to the NGO, thus allowing it to specifically target MCF-7 cells, human breast cancer cells with FA receptors. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT), onto the FA-conjugated NGO (FA-NGO) via pi-pi stacking and hydrophobic interactions is investigated. It is demonstrated that FA-NGO loaded with the two anticancer drugs shows specific targeting to MCF-7 cells, and remarkably high cytotoxicity compared to NGO loaded with either DOX or CPT only. Considering that the combined use of two or more drugs, a widely adopted clinical practice, often displays much better therapeutic efficacy than that of a single drug, the controlled loading and targeted delivery of mixed anticancer drugs using these graphene-based nanocarriers may find widespread application in biomedicine.


The association of fasting plasma sulfur-containing compounds with BMI, serum lipids and apolipoproteins.
Sulfur amino acids are recognized as potent modulators of lipid metabolism. Plasma total cysteine (tCys) is associated with fat mass, obesity and serum LDL-cholesterol and apolipoprotein (Apo)-B in large population studies. It is not known how fasting plasma concentrations of cysteine precursors and products relate to these associations in humans, given that sulfur-containing compounds (SCC) influence rodent weight gain and serum lipids. We investigated the cross-sectional associations of fasting plasma SCC (methionine, total homocysteine, cystathionine, tCys, taurine and total glutathione) with BMI and fasting serum lipids and apolipoproteins in 854 men and women with and without cardiovascular disease (CVD). In multiple linear regression analysis adjusted for age, gender, CVD and other SCC, neither methionine, taurine, nor total glutathione was associated with BMI. Plasma taurine was, however, inversely related to HDL-cholesterol (partial r = -0.12, p = 0.004) and its associated apoA1 (partial r = -0.18, p < 0.001). Plasma cystathionine correlated positively with triglycerides and BMI, while tCys positively correlated with total cholesterol, LDL-cholesterol (partial r = 0.20, p < 0.001) and its associated apoB. The associations of SCC with serum lipids were independent of BMI. tCys was also independently associated with BMI (partial r = 0.20, p < 0.001) after adjustment for other SCC, glucose, lipids and apolipoproteins. Fasting tCys is associated with BMI independently of metabolically related SCC. Elevation of plasma SCC is generally associated with an unfavorable lipid profile. The negative relations of plasma taurine with HDL-C and apoA1 deserve further investigation.


Prevalence of Undiagnosed Cardiovascular Risk Factors in Adults Aged 20 - 40: A Cross-Sectional Study in 2016 in Jeddah, Saudi Arabia.
Cardiovascular diseases (CVDs) are the first leading cause of death worldwide. In Saudi Arabia, CVDs are the major killers with a mortality rate of 46%. CVD risk factors are not exclusive to old populations. Thus, the purpose of this study was to approximately find the prevalence of these risk factors, particularly high blood pressure (HBP), high blood glucose (HBG), obesity, and smoking. This cross-sectional was conducted in May 2016 and took place in the Ambulatory Care Center of King Abdulaziz Medical City, Jeddah. We used a non-probability convenience sampling technique where only individuals aged 20 - 40 who were free of medical illnesses were included. We excluded pregnant women and people on medications that might interfere with our measurements. We obtained a brief history and measured blood pressure, blood glucose, height and weight. Data analysis was done in form of frequencies. Chi-square test was utilized to compare qualitative variables. P < 0.05 was used to determine statistical significance. A total of 507 participants were included (76.3% males and 23.7% females). All participants were between 20 and 40 with a mean age of 31.6 ± 6.06 SD. We found the prevalence of undiagnosed HBP to be 8.3% and males showed a significantly higher percentage (P < 0.001) when compared to females. HBG prevalence was only 0.6%. Regarding body mass index, the prevalence of overweight and obesity together was 66.3% and males showed significantly higher percentage in falling in this category (P < 0.001). Smoking prevalence was 37.9% with a significantly higher percentage among males (P < 0.001). CVD risk factors are apparently quite common in young adults. Efforts must be made to increase the public awareness regarding these risk factors. CVDs are not exclusive to old people. Thus, the public should appreciate this fact in order to prevent these risk factors by establishing healthy life-styles.


Massive fatal overdose of abrin with progressive encephalopathy.
Introduction: The jequirity bean (Abrus precatorius) seed contains abrin, a toxalbumin, that irreversibly binds the 60-s ribosomal subunit inhibiting protein synthesis. Neurologic manifestations of ingestions are rare.Case details: We present a case of a 20-year-old man with 24 h of vomiting, diarrhea and 2 h of hematemesis and hematochezia. He admitted to purchasing 1000 jequirity beans online, crushing and ingesting them 26 h prior to presentation in a suicide attempt. Over the next 2 days, he developed hallucinations, incomprehensible mumbling and grunting, disconjugate gaze with abnormal roving eye movements and a left gaze preference with his right eye deviated medially. There was a fine tremor of the upper extremities and he had brief episodes of choreoathetoid movements of his legs. A head CT was normal with no cerebral edema. He progressed to minimally responsive to noxious stimuli, and was unable to converse or follow commands and displayed increased choreoathetoid movements of his extremities. An electroencephalogram (EEG) showed only mild background slowing. Magnetic resonance imaging (MRI) was performed showing bilaterally symmetric signal abnormalities in the basal ganglia, brainstem, corpus callosum and corona radiata with diffuse leptomeningeal enhancement. The patient developed a tonic-clonic seizure followed by pulseless electrical activity, from which he was resuscitated. He was provided comfort care and died just under 5 days after his ingestion.Results: Urine analysis using liquid chromatography coupled to tandem mass spectrometry was positive for 8.84 ng/ml of l-abrine (4.96 ng l-abrine/mg creatinine) 61 h after admission to the hospital (approximately 87 h post-ingestion). Serum concentrations for l-abrine and ricinine were both below the limits of detection.Discussion: Ingestion of 1000 crushed jequirity beans purchased on the internet resulted in progressive encephalopathy and death.


Who are the essential and frontline workers?
Identifying essential and frontline workers and understanding their characteristics is useful for policymakers and researchers in targeting social insurance and safety net policies in response to the COVID-19 crisis and allocating scarce resources like personal protective equipment (PPE) and vaccines. We develop a working definition and provide data on the demographic and labor market composition of these workers. We first apply the official industry guidelines issued by the Department of Homeland Security (DHS) in March 2020 to microdata from the 2018 and 2019 American Community Survey to identify essential workers regardless of actual operation status of their industry. We then use the feasibility of work from home in the worker's occupation group (Dingel and Neiman 2020) to identify those most likely to be frontline workers who worked in-person early in the COVID-19 crisis in March/April 2020. In a third step, we exclude industries that were shut down or running under limited demand at that time (Vavra 2020). We find that the broader group of essential workers comprises a large share of the labor force and tends to mirror its demographic and labor market characteristics. In contrast, the narrower category of frontline workers is, on average, less educated, has lower wages, and has a higher representation of men, disadvantaged minorities, especially Hispanics, and immigrants. These results hold even when excluding industries that were shut down or operating at a limited level. Results for essential and frontline workers are similar when accounting for changes in the federal guidelines over time by using the December 2020 guidelines which include a few additional groups of workers, including the education sector.


Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity.
Legionella pneumophila, the causative agent of Legionnaires' disease, replicates as an intracellular parasite of amoebae and persists in the environment as a free-living microbe. Here we have analyzed the complete genome sequences of L. pneumophila Paris (3,503,610 bp, 3,077 genes), an endemic strain that is predominant in France, and Lens (3,345,687 bp, 2,932 genes), an epidemic strain responsible for a major outbreak of disease in France. The L. pneumophila genomes show marked plasticity, with three different plasmids and with about 13% of the sequence differing between the two strains. Only strain Paris contains a type V secretion system, and its Lvh type IV secretion system is encoded by a 36-kb region that is either carried on a multicopy plasmid or integrated into the chromosome. Genetic mobility may enhance the versatility of L. pneumophila. Numerous genes encode eukaryotic-like proteins or motifs that are predicted to modulate host cell functions to the pathogen's advantage. The genome thus reflects the history and lifestyle of L. pneumophila, a human pathogen of macrophages that coevolved with fresh-water amoebae.


Analysis of multiple folding routes of proteins by a coarse-grained dynamics model.
Langevin dynamics of a protein molecule with Go-type potentials is developed and used to analyze long time-scale events in the folding of cytochrome c. Several trajectories are generated, starting from random coil configurations and going to the native state, that are a few angstroms root mean square deviation (RMSD) from the native structure. The dynamics is controlled, to a large scale, by the two terminal helices that are in contact in the native state. These two helices form very early during folding, and depending on the trajectory, they either stabilize rapidly or break and re-form in going over steric barriers. The extended initial chain exhibits a rapid folding transition into a relatively compact shape, after which the helices are reorganized in a highly correlated manner. The time of formation of residue pair contacts strongly points to the hierarchical nature of folding; i.e., secondary structure forms first, followed by rearrangements of larger length scales at longer times. The kinetics of formation of native contacts is also analyzed, and the onset of a stable globular configuration, referred to as the molten globule in the literature, is identified. Predictions of the model are compared with extensive experimental data on cytochrome c.


Perceived stigma and mental health care seeking.
There is limited empirical evidence on the extent to which perceived public stigma prevents individuals from using mental health services, despite substantial recent policy interest in this issue. This study investigated associations between perceived public stigma and mental health care seeking. This study used cross-sectional survey data from a representative sample of undergraduate and graduate students (N=2,782) at one university. A five-item scale was used to assess perceived public stigma toward mental health service use. Perceived need for help in the past 12 months and current presence of depressive and anxiety disorders were also assessed. Perceived stigma was higher among males, older students, Asian and Pacific Islanders, international students, students with lower socioeconomic status backgrounds, and students with current mental health problems. Perceived stigma was also higher among those without any family members or friends who had used mental health services and among those who believed that therapy or medication is not very helpful. Perceived stigma was negatively associated with the likelihood of perceiving a need for mental health services, but only among younger students. Among those with probable depressive or anxiety disorders, there was no evidence that perceived stigma was associated with service use. These results suggest that, at least in this population, perceived stigma may not be as important a barrier to mental health care as the mental health policy discourse currently assumes.


Black-white differences in fracture rates.
To compare the incidence of all nonvertebral fractures between elderly blacks and whites, the authors conducted a retrospective cohort study among Tennessee Medicaid enrollees aged 65 years or more from 1987 through 1989. A previously validated computer algorithm identified 6,802 persons of black or white race with 7,645 new nonvertebral fractures. The incidence of all nonvertebral fractures in blacks was only half of that in whites. This finding persisted after the authors controlled for sex, age, and nursing home residence (relative risk = 0.4, 95% confidence interval 0.4-0.5). Rates were consistently lower among blacks within subgroups defined by these factors and for each of the 13 different fracture sites examined. The magnitude of the difference between blacks and whites in rates of all fractures combined and most site-specific fractures is similar to that previously reported for hip fractures. These consistent racial differences suggest a common underlying factor(s).


Measurement of flow velocity and inference of liquid viscosity in a microfluidic channel by fluorescence photobleaching.
We present a simple, noninvasive method for simultaneous measurement of flow velocity and inference of liquid viscosity in a microfluidic channel. We track the dynamics of a sharp front of photobleached fluorescent dye using a confocal microscope and measure the intensity at a single point downstream of the initial front position. We fit an exact solution of the advection diffusion equation to the fluorescence intensity recovery curve to determine the average flow velocity and the diffusion coefficient of the tracer dye. The dye diffusivity is correlated to solute concentration to infer rheological properties of the liquid. This technique provides a simple method for simultaneous elucidation of flow velocity and liquid viscosity in microchannels.


Mutational analysis of DNMT3A gene in acute leukemias and common solid cancers.
DNMT3A, a DNA methyltransferase that functions for de novo methylation, is important in development and many cellular processes related to tumorigenesis. Somatic mutations of DNMT3A gene, including recurrent mutations in its Arg-882, were recently reported in acute myelogenous leukemia (AML), strongly suggesting its role in development of AML. To see whether DNMT3A mutation occurs in other malignancies as well, we analyzed DNMT3A in 916 cancer tissues from 401 hematologic malignancies (AML, acute lymphoblastic leukemias (ALL), multiple myelomas and lymphomas) and 515 carcinomas (lung, breast, prostate, colorectal and gastric carcinomas) using a single-strand conformation polymorphism (SSCP) assay. We identified DNMT3A mutations, especially the Arg-882 mutations, in adulthood AML (9.4%). In addition, we found DNMT3A mutations in pre-B-ALL and three lung cancers at lower frequencies. Allelic loss of DNMT3A was frequently observed in most cancer types analyzed, including lymphomas (48.1%), gastric cancers (23.5%) and lung cancers (18.3%) irrespective of DNMT3A mutation. Also, loss of DNMT3A expression was common in lung cancers (46.4%), and was associated with the allelic loss. Our data indicate that DNMT3A gene is mutated mainly in AML, but it occurs in other cancers, such as ALL and lung cancer, despite the lower incidences. Also, the data suggest that DNMT3A is altered in many cancer types by various ways, including somatic mutations, allelic loss and loss of expression that might play roles in tumorigenesis.


Formation of a cytochrome c-nitrous oxide reductase complex is obligatory for N2O reduction by Paracoccus pantotrophus.
Nitrous oxide reductase (N2OR) catalyses the final step of bacterial denitrification, the two-electron reduction of nitrous oxide (N2O) to dinitrogen (N2). N2OR contains two metal centers; a binuclear copper center, CuA, that serves to receive electrons from soluble donors, and a tetranuclear copper-sulfide center, CuZ, at the active site. Stopped flow experiments at low ionic strengths reveal rapid electron transfer (kobs=150 s-1) between reduced horse heart (HH) cytochrome c and the CuA center in fully oxidized N2OR. When fully reduced N2OR was mixed with oxidized cytochrome c, a similar rate of electron transfer was recorded for the reverse reaction, followed by a much slower internal electron transfer from CuZ to CuA(kobs=0.1-0.4 s-1). The internal electron transfer process is likely to represent the rate-determining step in the catalytic cycle. Remarkably, in the absence of cytochrome c, fully reduced N2OR is inert towards its substrate, even though sufficient electrons are stored to initiate a single turnover. However, in the presence of reduced cytochrome c and N2O, a single turnover occurs after a lag-phase. We propose that a conformational change in N2OR is induced by its specific interaction with cytochrome c that in turn either permits electron transfer between CuA and CuZ or controls the rate of N2O decomposition at the active site.


Heterogeneous distribution of a diffusional tracer in the aortic wall of normal and atherosclerotic rabbits.
Tracer distribution as an index of nutritional support across the thoracic and abdominal aortas in rabbits in the presence or absence of atherosclerotic lesions was evaluated using [14C]antipyrine, a metabolically inert, diffusible indicator. Intimal plaques were produced by endothelial balloon denudation of the thoracic aorta and a 1% cholesterol diet. After a steady intravenous infusion of 200 microCi of [14C]antipyrine for 60 seconds, thoracic and abdominal aortas and the heart were excised, and autoradiograms of 20-microns-thick sections were quantified, using microcomputer-aided densitometry. Regional radioactivity and regional diffusional support, as an index of nutritional flow estimated from the timed collections of arterial blood, was 367 and 421 nCi.g-1 (82 and 106 ml.min-1.100 g-1) in thoracic aortic media of the normal and atherosclerotic rabbits, respectively. Radioactivity at the thickened intima was 179 nCi.g-1 (p less than 0.01 versus media). The gruel was noted at a deeper site within the thickened intima, and diffusional support here was 110 nCi.g-1 (p less than 0.01 versus an average radioactivity at the thickened intima). After ligating the intercostal arteries, regional tracer distribution in the media beneath the fibrofatty lesion, but not the plaque-free intima, was reduced to 46%. Thus, in the presence of advanced intimal thickening, the heterogeneous distribution of diffusional flow is prominent across the vessel wall, and abluminal routes are crucial to meet the increased demands of nutritional requirements.


Distinguishing age differences in knowledge, strategy use, and confidence during strategic skill acquisition.
The authors examined how age differences in strategy selection are related to associative learning deficits and metacognitive variables, including memory ability confidence. In Experiment 1, increases in memory reliance for performance of the noun-pair lookup task were compared with increases in noun-pair memory ability. In Experiment 2, memory reliance was assessed for noun pairs memorized prior to the task. In each experiment, older adults manifested a substantial delay in transition to a retrieval-based strategy despite comparable noun-pair knowledge. In Experiment 3, young and older adults reported comparable confidence ratings for the accuracy of each memory probe response. However, older adults reported lower confidence in their general ability to use the memory retrieval strategy, which correlated with avoidance of the retrieval strategy.


International travel-related control measures to contain the COVID-19 pandemic: a rapid review.
In late 2019, the first cases of coronavirus disease 2019 (COVID-19) were reported in Wuhan, China, followed by a worldwide spread. Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers. To assess the effectiveness of international travel-related control measures during the COVID-19 pandemic on infectious disease transmission and screening-related outcomes. We searched MEDLINE, Embase and COVID-19-specific databases, including the Cochrane COVID-19 Study Register and the WHO Global Database on COVID-19 Research to 13 November 2020. We considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across international borders during the COVID-19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). In this version we decided to focus on COVID-19 evidence only. Primary outcome categories were (i) cases avoided, (ii) cases detected, and (iii) a shift in epidemic development. Secondary outcomes were other infectious disease transmission outcomes, healthcare utilisation, resource requirements and adverse effects if identified in studies assessing at least one primary outcome. Two review authors independently screened titles and abstracts and subsequently full texts. For studies included in the analysis, one review author extracted data and appraised the study. At least one additional review author checked for correctness of data. To assess the risk of bias and quality of included studies, we used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool for observational studies concerned with screening, and a bespoke tool for modelling studies. We synthesised findings narratively. One review author assessed the certainty of evidence with GRADE, and several review authors discussed these GRADE judgements. Overall, we included 62 unique studies in the analysis; 49 were modelling studies and 13 were observational studies. Studies covered a variety of settings and levels of community transmission. Most studies compared travel-related control measures against a counterfactual scenario in which the measure was not implemented. However, some modelling studies described additional comparator scenarios, such as different levels of stringency of the measures (including relaxation of restrictions), or a combination of measures. Concerns with the quality of modelling studies related to potentially inappropriate assumptions about the structure and input parameters, and an inadequate assessment of model uncertainty. Concerns with risk of bias in observational studies related to the selection of travellers and the reference test, and unclear reporting of certain methodological aspects. Below we outline the results for each intervention category by illustrating the findings from selected outcomes. Travel restrictions reducing or stopping cross-border travel (31 modelling studies) The studies assessed cases avoided and shift in epidemic development. We found very low-certainty evidence for a reduction in COVID-19 cases in the community (13 studies) and cases exported or imported (9 studies). Most studies reported positive effects, with effect sizes varying widely; only a few studies showed no effect. There was very low-certainty evidence that cross-border travel controls can slow the spread of COVID-19. Most studies predicted positive effects, however, results from individual studies varied from a delay of less than one day to a delay of 85 days; very few studies predicted no effect of the measure. Screening at borders (13 modelling studies; 13 observational studies) Screening measures covered symptom/exposure-based screening or test-based screening (commonly specifying polymerase chain reaction (PCR) testing), or both, before departure or upon or within a few days of arrival. Studies assessed cases avoided, shift in epidemic development and cases detected. Studies generally predicted or observed some benefit from screening at borders, however these varied widely. For symptom/exposure-based screening, one modelling study reported that global implementation of screening measures would reduce the number of cases exported per day from another country by 82% (95% confidence interval (CI) 72% to 95%) (moderate-certainty evidence). Four modelling studies predicted delays in epidemic development, although there was wide variation in the results between the studies (very low-certainty evidence). Four modelling studies predicted that the proportion of cases detected would range from 1% to 53% (very low-certainty evidence). Nine observational studies observed the detected proportion to range from 0% to 100% (very low-certainty evidence), although all but one study observed this proportion to be less than 54%. For test-based screening, one modelling study provided very low-certainty evidence for the number of cases avoided. It reported that testing travellers reduced imported or exported cases as well as secondary cases. Five observational studies observed that the proportion of cases detected varied from 58% to 90% (very low-certainty evidence). Quarantine (12 modelling studies) The studies assessed cases avoided, shift in epidemic development and cases detected. All studies suggested some benefit of quarantine, however the magnitude of the effect ranged from small to large across the different outcomes (very low- to low-certainty evidence). Three modelling studies predicted that the reduction in the number of cases in the community ranged from 450 to over 64,000 fewer cases (very low-certainty evidence). The variation in effect was possibly related to the duration of quarantine and compliance. Quarantine and screening at borders (7 modelling studies; 4 observational studies) The studies assessed shift in epidemic development and cases detected. Most studies predicted positive effects for the combined measures with varying magnitudes (very low- to low-certainty evidence). Four observational studies observed that the proportion of cases detected for quarantine and screening at borders ranged from 68% to 92% (low-certainty evidence). The variation may depend on how the measures were combined, including the length of the quarantine period and days when the test was conducted in quarantine. With much of the evidence derived from modelling studies, notably for travel restrictions reducing or stopping cross-border travel and quarantine of travellers, there is a lack of 'real-world' evidence. The certainty of the evidence for most travel-related control measures and outcomes is very low and the true effects are likely to be substantially different from those reported here. Broadly, travel restrictions may limit the spread of disease across national borders. Symptom/exposure-based screening measures at borders on their own are likely not effective; PCR testing at borders as a screening measure likely detects more cases than symptom/exposure-based screening at borders, although if performed only upon arrival this will likely also miss a meaningful proportion of cases. Quarantine, based on a sufficiently long quarantine period and high compliance is likely to largely avoid further transmission from travellers. Combining quarantine with PCR testing at borders will likely improve effectiveness. Many studies suggest that effects depend on factors, such as levels of community transmission, travel volumes and duration, other public health measures in place, and the exact specification and timing of the measure. Future research should be better reported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel-related control measures from a societal perspective.


Hormonal regulators of food intake and weight gain in Parkinson's disease after subthalamic nucleus stimulation.
Weight gain has been reported in patients with Parkinson's disease (PD) treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). To evaluate the influence of STN-DBS on weight changes, we studied food-related hormones. Anthropometric parameters and food-related hormones (leptin, adiponectin, resistin, ghrelin, cortisol, insulin, and thyroid stimulating hormone) were measured in 27 patients with STN-DBS during a 12 month period following electrode implantation. Besides marked motor improvements on STN-DBS, PD patients significantly gained weight. The mean weight gain at 12 months was 5.2±(SD)5.8 kg. A significant decrease in cortisol levels compared to baseline appeared at month 2 and persisted at 12 months (p<0.01, corrected), with no significant changes in other hormones tested. Changes in peripheral food-related hormones do not appear to cause weight gain in PD patients. Direct effects of STN-DBS on hypothalamic catabolic/anabolic peptide balance remain hypothetical and necessitate further elucidation.


Minibus taxi drivers' sexual beliefs and practices associated with HIV infection and AIDS in KwaZulu- Natal, South Africa.
Risky sexual behaviours in South Africa are a major contributing factor to the spread of HIV infection and AIDS. HIV infection amongst minibus taxi drivers is a concern, because these people belong to an occupational group that exhibits risky behaviours due to the demands of their work. Given the high vulnerability of minibus taxi drivers, exploring the sexual beliefs and health-related sexual practices of this group will assist in planning targeted interventions. The objectives of this study were to assess the level of knowledge, beliefs and practices regarding HIV infection and AIDS amongst minibus taxi drivers. An exploratory descriptive study was conducted using a pre-tested questionnaire to explore and describe sexual beliefs and practices associated with HIV infection and AIDS in a convenience sample of 175 minibus taxi drivers. Permission to undertake the study was obtained from the KwaZulu-Natal Taxi Alliance and individuals who participated in the study. Data analysis were analysed using the Statistical Package for Social Sciences 13.0. The study revealed that minibus taxi drivers are one of the high- risk groups in the spread of HIV infection and AIDS; they lack necessary education and need attention in relation to control and prevention of the spread of HIV and AIDS. Multiple sexual partners are relatively common amongst the minibus taxi drivers. Violence against women and even forceful sexual intercourse in the belief that women should tolerate it to keep the family together was reported. There is a need for intervention programmes with a focus on minibus taxi drivers and similar high-risk groups. Prevention activities should incorporate the distribution of condoms amongst this group and HIV prevention educational programmes, as well as creating mechanisms for accessing circumcision by the minibus taxi drivers.


Development and validity testing of the Adolescent Health Literacy Questionnaire (AHLQ): Protocol for a mixed methods study within the Irish school setting.
Health literacy research has focused predominantly on the adult population, and much less is understood about this concept from an adolescent perspective. The tools currently available to measure adolescent health literacy have been adapted from adult versions. This limits their applicability to young people because of the developmental characteristics that impact on adolescents' behaviour, including impulse control and judgement skills. This protocol describes the intended development and validity testing of a questionnaire to measure health literacy in adolescents. This protocol describes this mixed methods study that has three phases: the first phase will involve grounded research with adolescents using qualitative group interviews, co-design and concept mapping workshops to understand what health and healthy behaviours mean to adolescents and to explore their health literacy needs and the potential domains for the questionnaire. The draft health literacy domains identified will be presented to the youth advisory panel, and the questionnaire will be altered based on their feedback. Cognitive pretesting of the questionnaire items will also be conducted. Phase 2 will involve piloting the questionnaire to a two-stage random sample of young people in five urban and rural schools in Ireland. Test-retest reliability will be conducted using Pearson correlation coefficient. Confirmatory factor analysis will also be conducted to analyse the psychometric properties of the questionnaire. Phase 3 will involve the questionnaire being rolled out to a nationally representative sample of adolescents (n=6052) in Ireland to assess their levels of health literacy. Ethical approval to conduct this study has been granted from the University College Dublin Human Research Ethics Committee - Sciences (LS-20-08). Informed assent from adolescents and informed consent from parents/guardians will be sought. The findings of this research will be disseminated at national and international conferences, as well as through publication in peer-reviewed journals.


Music-based therapeutic interventions for people with dementia.
Dementia is a clinical syndrome with a number of different causes which is characterised by deterioration in cognitive, behavioural, social and emotional functions. Pharmacological interventions are available but have limited effect to treat many of the syndrome's features. Less research has been directed towards non-pharmacological treatments. In this review, we examined the evidence for effects of music-based interventions. To assess the effects of music-based therapeutic interventions for people with dementia on emotional well-being including quality of life, mood disturbance or negative affect, behavioural problems, social behaviour and cognition at the end of therapy and four or more weeks after the end of treatment. We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG) on 19 June 2017 using the terms: music therapy, music, singing, sing, auditory stimulation. Additional searches were carried out on 19 June 2017 in the major healthcare databases MEDLINE, Embase, PsycINFO, CINAHL and LILACS; and in trial registers and grey literature sources. We included randomised controlled trials of music-based therapeutic interventions (at least five sessions) for people with dementia that measured any of our outcomes of interest. Control groups either received usual care or other activities with or without music. Two review authors worked independently to screen the retrieved studies against the inclusion criteria and then to extract data and assess methodological quality of the included studies. If necessary, we contacted trial authors to ask for additional data, including relevant subscales, or for other missing information. We pooled data using random-effects models. We included 22 studies with 1097 randomised participants. Twenty-one studies with 890 participants contributed data to meta-analyses. Participants in the studies had dementia of varying degrees of severity, and all were resident in institutions. Seven studies delivered an individual music intervention; the other studies delivered the intervention to groups of participants. Most interventions involved both active and receptive musical elements. The methodological quality of the studies varied. All were at high risk of performance bias and some were at high risk of detection or other bias.At the end of treatment, we found low-quality evidence that the interventions may improve emotional well-being and quality of life (standardised mean difference (SMD) 0.32, 95% confidence interval (CI) 0.02 to 0.62; 9 studies, 348 participants) and reduce anxiety (SMD -0.43, 95% CI -0.72 to -0.14; 13 studies, 478 participants). We found low-quality evidence that music-based therapeutic interventions may have little or no effect on cognition (SMD 0.15, 95% CI -0.06 to 0.36; 7 studies, 350 participants). There was moderate-quality evidence that the interventions reduce depressive symptoms (SMD -0.27, 95% CI -0.45 to -0.09; 11 studies, 503 participants) and overall behaviour problems (SMD -0.23, 95% CI -0.46 to -0.01; 10 studies, 442 participants), but do not decrease agitation or aggression (SMD -0.07, 95% CI -0.24 to 0.10; 14 studies, 626 participants). The quality of the evidence on social behaviour was very low, so effects were very uncertain.The evidence for long-term outcomes measured four or more weeks after the end of treatment was of very low quality for anxiety and social behaviour, and for the other outcomes, it was of low quality for little or no effect (with small SMDs, between 0.03 and 0.34). Providing people with dementia who are in institutional care with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms and improves overall behavioural problems at the end of treatment. It may also improve emotional well-being and quality of life and reduce anxiety, but may have little or no effect on agitation or aggression or on cognition. We are uncertain about effects on social behaviour and about long-term effects. Future studies should examine the duration of effects in relation to the overall duration of treatment and the number of sessions.


Insecticide-treated net distribution in Western Kenya: impacts related to COVID-19 and health worker strikes.
We examined the impact of coronavirus disease (COVID) mitigation, supply and distribution interruptions on the delivery of long-lasting insecticide-treated nets (LLINs) in Western Kenya. The median monthly distribution of LLINs declined during COVID mitigation strategies (March-July 2020) and during the health worker strikes (December 2020-February 2021). Recovery periods followed initial declines, indicative of a 'catching up' on missed routine distribution. Mass community campaigns were delayed by 10 months. These observations offer encouragement for routine net distribution resilience, but complete interruptions of planned mass distributions require alternate strategies during pandemics.


Enhancement of microbubble generation in a pressurized dissolution process by packing the nozzle with porous ceramics.
The pressurized dissolution method is often used for microbubble generation. However, the main disadvantage of this method is that a large amount of energy (more than 0.3 MPa) is required to generate many microbubbles, each of which have a diameter of several dozen μm. To overcome this problem, we investigated the effectiveness of porous ceramic when used as the packing material in the pressurized dissolution method. The results showed that when compared with the control (no porous ceramics), use of porous ceramics resulted in a 39% increase in the number of microbubbles. Furthermore, when this system was used for the flotation separation of artificial suspended solids and activated sludge, the level of separation achieved with porous ceramics at 0.15 MPa was the same as that achieved using no porous ceramics at 0.25 MPa. It was estimated that the use of porous ceramics led to a 40% reduction in the energy required for the dissolved air flotation, with subsequent decreases in the operating cost.


Integrating Bayesian networks and geographic information systems: good practice examples.
Bayesian networks (BNs) are becoming increasingly common in problems with spatial aspects. The degree of spatial involvement may range from spatial mapping of BN outputs based on nodes in the BN that explicitly involve geographic features, to integration of different networks based on geographic information. In these situations, it is useful to consider how geographic information systems (GISs) could be used to enhance the conceptualization, quantification, and prediction of BNs. Here, we discuss some techniques that may be used to integrate GIS and BN models, with reference to some recent literature which illustrate these approaches. We then reflect on 2 case studies based on our own experience. The first involves the integration of GIS and a BN to assess the scientific factors associated with initiation of Lyngbya majuscula, a cyanobacterium that occurs in coastal waterways around the world. The 2nd case study involves the use of GISs as an aid for eliciting spatially informed expert opinion and expressing this information as prior distributions for a Bayesian model and as input into a BN. Elicitator, the prototype software package we developed for achieving this, is also briefly described. Whereas the 1st case study demonstrates a GIS-data driven specification of conditional probability tables for BNs with complete geographical coverage for all the data layers involved, the 2nd illustrates a situation in which we do not have complete coverage and we are forced to extrapolate based on expert judgement.


The solubilisation of boar sperm membranes by different detergents - a microscopic, MALDI-TOF MS, (31)P NMR and PAGE study on membrane lysis, extraction efficiency, lipid and protein composition.
Detergents are often used to isolate proteins, lipids as well as "detergent-resistant membrane domains" (DRMs) from cells. Different detergents affect different membrane structures according to their physico-chemical properties. However, the effects of different detergents on membrane lysis of boar spermatozoa and the lipid composition of DRMs prepared from the affected sperm membranes have not been investigated so far. Spermatozoa were treated with the selected detergents Pluronic F-127, sodium cholate, CHAPS, Tween 20, Triton X-100 and Brij 96V. Different patterns of membrane disintegration were observed by light and electron microscopy. In accordance with microscopic data, different amounts of lipids and proteins were released from the cells by the different detergents. The biochemical methods to assay the phosphorus and cholesterol contents as well as 31P NMR to determine the phospholipids were not influenced by the presence of detergents since comparable amounts of lipids were detected in the organic extracts from whole cell suspensions after exposure to each detergent. However, matrix-assisted laser desorption and ionization time-of-flight mass spectrometry applied to identify phospholipids was essentially disturbed by the presence of detergents which exerted particular suppression effects on signal intensities. After separation of the membrane fractions released by detergents on a sucrose gradient only Triton X-100 and sodium cholate produced sharp turbid DRM bands. Only membrane solubilisation by Triton X-100 leads to an enrichment of cholesterol, sphingomyelin, phosphatidylinositol and phosphatidylethanolamine in a visible DRM band accompanied by a selective accumulation of proteins. The boar sperm membranes are solubilised to a different extent by the used detergents. Particularly, the very unique DRMs isolated after Triton X-100 exposure are interesting candidates for further studies regarding the architecture of sperm.


The prevalence and determinants of active tuberculosis among diabetes patients in Cape Town, South Africa, a high HIV/TB burden setting.
Studies addressing the association between diabetes mellitus (DM) and tuberculosis (TB) in sub-Saharan Africa are limited. We assessed the prevalence of active TB among DM patients at a primary care clinic, and identified risk factors for prevalent TB. A cross-sectional study was conducted in adult DM patients attending a clinic in Khayelitsha, Cape Town. Participants were screened for active TB (symptom screening and microbiological diagnosis) and HIV. Among 440 DM patients screened, the active TB prevalence was 3.0% (95% CI 1.72-5.03). Of the 13 prevalent TB cases, 53.9% (n = 7; 95% CI 27.20-78.50) had no TB symptoms, and 61.5% (n = 8; 95% CI 33.30-83.70) were HIV-1 co-infected. There were no significant differences in either fasting plasma glucose or HbA1c levels between TB and non-TB participants. On multivariate analysis, HIV-1 infection (OR 11.3, 95% CI 3.26-39.42) and hemoptysis (OR 31.4, 95% CI 3.62-273.35) were strongly associated with prevalent active TB, with no differences in this association by age or gender. The prevalence of active TB among DM patients was 4-fold higher than the national prevalence; suggesting the need for active TB screening, particularly if hemoptysis is reported. Our results highlight the importance of HIV screening in this older population group. The high prevalence of sub-clinical TB among those diagnosed with TB highlights the need for further research to determine how best to screen for active TB in high-risk TB/HIV population groups and settings.