Work-related burnout, job satisfaction, intent to leave, and nurse-assessed quality of care among travel nurses.
This research study examines work-related burnout, job satisfaction, nurse-assessed quality of care, and intent to leave in travel nurses, a population that has not been studied previously. Travel nurses are frequently used to supplement nursing staff in acute care hospitals, especially in times of shortage--understanding their satisfaction with the job may further illuminate the problem of nurse job dissatisfaction in general. Ordinary least-squares regression analyses were used to examine the influence of nurse and workplace characteristics on work-related burnout, job satisfaction, intent to leave, and perceived quality of care. Quality of care and job satisfaction were significantly influenced by whether a hospital held Magnet designation. As the number of patients cared for increases, there was a significant increase in work-related burnout. Work-related burnout was also significantly lower for nurses working in California. The results of this study suggest that different workplace characteristics influence the perceptions of quality of care provided at a hospital facility and the degree to which a nurse is either burned out or satisfied with his/her job.


Interaction of bovine serum albumin and lysozyme with stainless steel studied by time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy.
An in-depth mechanistic understanding of the interaction between stainless steel surfaces and proteins is essential from a corrosion and protein-induced metal release perspective when stainless steel is used in surgical implants and in food applications. The interaction between lysozyme (LSZ) from chicken egg white and bovine serum albumin (BSA) and AISI 316L stainless steel surfaces was studied ex situ by means of X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) after different adsorption time periods (0.5, 24, and 168 h). The effect of XPS measurements, storage (aging), sodium dodecyl sulfate (SDS), and elevated temperature (up to 200 °C) on the protein layers, as well as changes in surface oxide composition, were investigated. Both BSA and LSZ adsorption induced an enrichment of chromium in the oxide layer. BSA induced significant changes to the entire oxide, while LSZ only induced a depletion of iron at the utmost layer. SDS was not able to remove preadsorbed proteins completely, despite its high concentration and relatively long treatment time (up to 36.5 h), but induced partial denaturation of the protein coatings. High-temperature treatment (200 °C) and XPS exposure (X-ray irradiation and/or photoelectron emission) induced significant denaturation of both proteins. The heating treatment up to 200 °C removed some proteins, far from all. Amino acid fragment intensities determined from ToF-SIMS are discussed in terms of significant differences with adsorption time, between the proteins, and between freshly adsorbed and aged samples. Stainless steel-protein interactions were shown to be strong and protein-dependent. The findings assist in the understanding of previous studies of metal release and surface changes upon exposure to similar protein solutions.


Readmission and length of stay after total hip arthroplasty in a national Medicare sample.
Evaluation of hospital readmissions after total hip arthroplasty may help improve patient safety and cost reduction. This study investigates the rates and reasons for readmission as well as length of hospital stay (LOS) for 1802 total hip arthroplasty patients from 2002 to 2007. Data were abstracted from the Medicare Patient Safety Monitoring System. The overall 30-day rate of readmission was 6.8%. There was no difference in readmission rate from 2002 to 2004 (7.1%) to 2005 to 2007 (6.3%) (odds ratio, 0.90; 95% confidence interval, 0.63-1.30; P = .58). The overall mean LOS was 4.2 ± 2.2 days. There was a significant reduction in LOS from 2002 to 2004 (4.4 ± 2.5 days) to 2005 to 2007 (3.8 ± 1.7 days) (odds ratio, 1.28; 95% confidence interval, 1.25-1.31; P < .0001). The most common causes for readmission were cardiac related. A reduction in LOS was not associated with an increase in the rate of readmission in this sample. Efforts to optimize cardiac status before discharge may lead to lower rates of readmission in the future.


Positive prevention: contemporary issues facing HIV positive people negotiating sex in the UK.
Over 40,000 people are now living with diagnosed HIV in the UK. The term 'positive prevention' has been coined to describe HIV prevention that focuses on people living with an HIV diagnosis. There is uncertainty, however, about how people with HIV manage risk and how their ability to prevent the transmission of HIV is linked to their mental health and social circumstances. We analysed 44 individual and three group interviews with the people most affected by HIV in the UK: black African heterosexual men and women and gay men (mostly white). We found that participants had similar as well as contextually different needs when it came to negotiating safe sex, assimilating prevention knowledge. The themes that emerged included taking 'additional responsibility' for partners, negotiating with partners who are willing to have unprotected (anal or vaginal) sex, links with mental health, constructing the moral 'other' and power differences. We conclude with a discussion of the priorities for positive prevention for men and women living with diagnosed HIV in the UK.


Metabarcoding for the parallel identification of several hundred predators and their prey: Application to bat species diet analysis.
Assessing diet variability is of main importance to better understand the biology of bats and design conservation strategies. Although the advent of metabarcoding has facilitated such analyses, this approach does not come without challenges. Biases may occur throughout the whole experiment, from fieldwork to biostatistics, resulting in the detection of false negatives, false positives or low taxonomic resolution. We detail a rigorous metabarcoding approach based on a short COI minibarcode and two-step PCR protocol enabling the "all at once" taxonomic identification of bats and their arthropod prey for several hundreds of samples. Our study includes faecal pellets collected in France from 357 bats representing 16 species, as well as insect mock communities that mimic bat meals of known composition, negative and positive controls. All samples were analysed using three replicates. We compare the efficiency of DNA extraction methods, and we evaluate the effectiveness of our protocol using identification success, taxonomic resolution, sensitivity and amplification biases. Our parallel identification strategy of predators and prey reduces the risk of mis-assigning prey to wrong predators and decreases the number of molecular steps. Controls and replicates enable to filter the data and limit the risk of false positives, hence guaranteeing high confidence results for both prey occurrence and bat species identification. We validate 551 COI variants from arthropod including 18 orders, 117 family, 282 genus and 290 species. Our method therefore provides a rapid, resolutive and cost-effective screening tool for addressing evolutionary ecological issues or developing "chirosurveillance" and conservation strategies.


Structure of the hexameric HerA ATPase reveals a mechanism of translocation-coupled DNA-end processing in archaea.
The HerA ATPase cooperates with the NurA nuclease and the Mre11-Rad50 complex for the repair of double-strand DNA breaks in thermophilic archaea. Here we extend our structural knowledge of this minimal end-resection apparatus by presenting the first crystal structure of hexameric HerA. The full-length structure visualizes at atomic resolution the N-terminal HerA-ATP synthase domain and a conserved C-terminal extension, which acts as a physical brace between adjacent protomers. The brace also interacts in trans with nucleotide-binding residues of the neighbouring subunit. Our observations support a model in which the coaxial interaction of the HerA ring with the toroidal NurA dimer generates a continuous channel traversing the complex. HerA-driven translocation would propel the DNA towards the narrow annulus of NurA, leading to duplex melting and nucleolytic digestion. This system differs substantially from the bacterial end-resection paradigms. Our findings suggest a novel mode of DNA-end processing by this integrated archaeal helicase-nuclease machine.


The pore structure and gating mechanism of K2P channels.
Two-pore domain (K2P) potassium channels are important regulators of cellular electrical excitability. However, the structure of these channels and their gating mechanism, in particular the role of the bundle-crossing gate, are not well understood. Here, we report that quaternary ammonium (QA) ions bind with high-affinity deep within the pore of TREK-1 and have free access to their binding site before channel activation by intracellular pH or pressure. This demonstrates that, unlike most other K(+) channels, the bundle-crossing gate in this K2P channel is constitutively open. Furthermore, we used QA ions to probe the pore structure of TREK-1 by systematic scanning mutagenesis and comparison of these results with different possible structural models. This revealed that the TREK-1 pore most closely resembles the open-state structure of KvAP. We also found that mutations close to the selectivity filter and the nature of the permeant ion profoundly influence TREK-1 channel gating. These results demonstrate that the primary activation mechanisms in TREK-1 reside close to, or within the selectivity filter and do not involve gating at the cytoplasmic bundle crossing.


Inpatient physical activity across a large university city hospital: a behavioral mapping study.
Physical inactivity is common during hospitalization. Physical activity has been described in different inpatient populations but never across a hospital. To describe inpatient movement behavior and associated factors throughout a single university hospital. A prospective observational study was performed. Patients admitted to clinical wards were included. Behavioral mapping was undertaken for each participant between 9AM and 4PM. The location, physical activity, daily activity, and company of participants were described. Barriers to physical activity were examined using linear regression analyses. In total, 345 participants from 19 different wards were included. The mean (SD) age was 61 (16) years and 57% of participants were male. In total, 65% of participants were able to walk independently. On average participants spent 86% of observed time in their room and 10% of their time moving. A physiotherapist or occupational therapist was present during 1% of the time, nursing staff and family were present 11% and 13%, respectively. Multivariate regression analysis showed the presence of an intravenous line (p = .039), urinary catheter (p = .031), being female (p = .034), or being dependent on others for walking (p = .016) to be positively associated with the time spent in bed. Age > 65, undergoing surgery, receiving encouragement by a nurse or physician, reporting a physical complaint or pain were not associated with the time spent in bed (P > .05). As family members and nursing staff spend more time with patients than physiotherapists or occupational therapists, increasing their involvement might be an important next step in the promotion of physical activity.


Haplotype-based analysis of common variation in the growth hormone receptor gene and prostate cancer risk.
The growth hormone receptor (GHR) is potentially involved in prostate cancer through its role in stimulating insulin-like growth factor I production and its cellular effects on prostate epithelium. We have used a haplotype-based tagging approach within CAncer Prostate Sweden, a large retrospective case-control study of 2,863 cases and 1,737 controls to investigate if genetic variation in the GHR gene influences prostate cancer risk. One haplotype in the 3' region of the GHR gene was found associated with prostate cancer risk in elderly men (>65 years old at the time of diagnosis), with heterozygote haplotype carriers having an odds ratio of 1.65 (95% confidence interval, 1.21-2.16; P = 0.0009, P(corrected) = 0.03). GHR function has been implicated in the determination of body mass index. Interestingly, the same haplotype associated with risk in the 3' end of the GHR gene was also associated with a decrease in body mass index in controls (P = 0.003, P(corrected) = 0.05), possibly indicating some functionality with this haplotype. These results suggest that whereas genetic variation in the GHR gene does not seem to play a major role in prostate cancer etiology, one haplotype in the 3' region may be potentially relevant to cases with later onset of prostate cancer.


Pneumomediastinum as a primary manifestation of chronic hypersensitivity pneumonitis.
Patients with chronic hypersensitivity pneumonitis (HP) can present with an insidious onset of their disease without typical fluctuating flu-like symptoms, and there are only signs of chronic respiratory failure caused by the progressive fibrotic lung disease. A 45-year-old man with a pneumomediastinum and interstitial lung disease was referred for further investigations and therapy. No traumatic event or interventional procedure had occurred prior to referral. The patient had been working in farming for almost 20 years and was exposed in childhood by his father to pigeon breeding from childhood until 20 years ago. He reported dyspnea on exercise for the previous 2 years. High-resolution CT of the lung showed a pneumomediastinum and a fibrotic interstitial lung disease without dominating ground-glass opacities. Specific IgG antibodies were markedly elevated against molds and avian antigens. Bronchoalveolar lavage demonstrated a slightly lymphocytic and neutrophilic alveolitis. After recovering from the pneumomediastinum, an open lung biopsy was performed and a UIP-pattern was detected. An inhalative challenge with hay from the work-place was positive. A diagnosis of chronic farmer's lung was made. Pneumomediastinum has been described in other fibrotic lung diseases, but until now it has not been described as a primary manifestation of chronic fibrotic HP. Particularly in cases of concurrent antigen sources, an inhalative challenge could be done, even in a chronic course of HP.


Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11.
Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the pro-metastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis.


Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation-Induced Mouse Memory Impairment Model.
Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory-improving effects in normal mice and scopolamine-induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 μmol/kg; 40 μmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14-day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homogenized, and levels and activities of antioxidant defense biomarkers were evaluated to determine the level of oxidative stress. The results revealed that Rh1 prevented cognitive impairment induced by SD, and its ability to reduce oxidative stress in cortex and hippocampus may contribute to the mechanism of action. Copyright © 2017 John Wiley & Sons, Ltd.


Interventions Must Be Realistic to Be Useful and Completed in Family Medicine.
Being realistic while helping our patients is this issue's theme. Given the volume of tasks required in family medicine, recommendations for improvements in direct care or care measurement cannot just be evidence-based but must also be realistic. On the list of realistic: ordering antipsychotics for symptoms of dementia in the elderly, despite recommendations to not do so; ordering antidepressants without fear that the patient could develop hypertension; mental health care providers in primary care offices; forced choice for opioid management; plus agenda setting for visit efficiency. Not yet realistic: trigger tools to identify adverse events, and pharmacist recommendations related to pain management before opioid visits. Pneumococcal vaccine compliance is only realistic if recommendations are not recurrently changed, are paid for, and if prior immunizations are known. Increasing task delegation to prevent clinician burnout is not realistic if it burns out the nurses, or if the helpful scribes cannot be afforded. Helpful, yet questionably realistic: Primary care clinician involvement for patients in intensive care units and their families, and problem-solving therapy by family physicians. And, let us add 'frightening': few international medical school graduates to serve the underserved. The most frequent diagnoses and most critical diagnoses in family medicine are elucidated.


Viewing the body modulates neural mechanisms underlying sustained spatial attention in touch.
Cross-modal links between vision and touch have been extensively shown with a variety of paradigms. The present event-related potential (ERP) study aimed to clarify whether neural mechanisms underlying sustained tactile-spatial attention may be modulated by visual input, and the sight of the stimulated body part (i.e. hands) in particular. Participants covertly attended to one of their hands throughout a block to detect infrequent tactile target stimuli at that hand while ignoring tactile targets at the unattended hand, and all tactile non-targets. In different blocks, participants performed this task under three viewing conditions: full vision; hands covered from view; and blindfolded. When the participants' hands were visible attention was found to modulate somatosensory ERPs at early latencies (i.e. in the time range of the somatosensory P100 and the N140 components), as well as at later time intervals, from 200 ms after stimulus onset. By contrast, when participants were blindfolded and, crucially, even when only their hands were not visible, attentional modulations were found to arise only at later intervals (i.e. from 200 ms post-stimulus), while earlier somatosensory components were not affected by spatial attention. The behavioural results tallied with these electrophysiological findings, showing faster response times to tactile targets under the full vision condition compared with conditions when participants' hands were covered, and when participants were blindfolded. The results from this study provide the first evidence of the profound impact of vision on mechanisms underlying sustained tactile-spatial attention, which is enhanced by the sight of the body parts (i.e. hands).


Prior experience biases subcortical sensitivity to sound patterns.
To make sense of our ever-changing world, our brains search out patterns. This drive can be so strong that the brain imposes patterns when there are none. The opposite can also occur: The brain can overlook patterns because they do not conform to expectations. In this study, we examined this neural sensitivity to patterns within the auditory brainstem, an evolutionarily ancient part of the brain that can be fine-tuned by experience and is integral to an array of cognitive functions. We have recently shown that this auditory hub is sensitive to patterns embedded within a novel sound stream, and we established a link between neural sensitivity and behavioral indices of learning [Skoe, E., Krizman, J., Spitzer, E., & Kraus, N. The auditory brainstem is a barometer of rapid auditory learning. Neuroscience, 243, 104-114, 2013]. We now ask whether this sensitivity to stimulus statistics is biased by prior experience and the expectations arising from this experience. To address this question, we recorded complex auditory brainstem responses (cABRs) to two patterned sound sequences formed from a set of eight repeating tones. For both patterned sequences, the eight tones were presented such that the transitional probability (TP) between neighboring tones was either 33% (low predictability) or 100% (high predictability). Although both sequences were novel to the healthy young adult listener and had similar TP distributions, one was perceived to be more musical than the other. For the more musical sequence, participants performed above chance when tested on their recognition of the most predictable two-tone combinations within the sequence (TP of 100%); in this case, the cABR differed from a baseline condition where the sound sequence had no predictable structure. In contrast, for the less musical sequence, learning was at chance, suggesting that listeners were "deaf" to the highly predictable repeating two-tone combinations in the sequence. For this condition, the cABR also did not differ from baseline. From this, we posit that the brainstem acts as a Bayesian sound processor, such that it factors in prior knowledge about the environment to index the probability of particular events within ever-changing sensory conditions.


NRT1.1B is associated with root microbiota composition and nitrogen use in field-grown rice.
Nitrogen-use efficiency of indica varieties of rice is superior to that of japonica varieties. We apply 16S ribosomal RNA gene profiling to characterize root microbiota of 68 indica and 27 japonica varieties grown in the field. We find that indica and japonica recruit distinct root microbiota. Notably, indica-enriched bacterial taxa are more diverse, and contain more genera with nitrogen metabolism functions, than japonica-enriched taxa. Using genetic approaches, we provide evidence that NRT1.1B, a rice nitrate transporter and sensor, is associated with the recruitment of a large proportion of indica-enriched bacteria. Metagenomic sequencing reveals that the ammonification process is less abundant in the root microbiome of the nrt1.1b mutant. We isolated 1,079 pure bacterial isolates from indica and japonica roots and derived synthetic communities (SynComs). Inoculation of IR24, an indica variety, with an indica-enriched SynCom improved rice growth in organic nitrogen conditions compared with a japonica-enriched SynCom. The links between plant genotype and root microbiota membership established in this study will inform breeding strategies to improve nitrogen use in crops.


SU-E-T-194: Evaluation and Simulation of Shallow Depth Skin Dose from Couch Top in Radiotherapy.
When the treatment couch-top contacts the patient, the skin dose to the patient also generates clinical significance as the radiation beam passes through the couch. In this study, the effect on entrance shallow depth dose was investigated for the carbon fiber exact couch-top from Varian Medical System. An Accredited Dosimetry Calibration Laboratory (ADCL) calibrated PTW parallel-plate thin-window chamber was used to measure the doses in the build-up region. Firstly, the shallow depth doses at different field sizes, depths and incident angle beams were measured for 6MV and 18MV photon beams. To test the couch top contribution to the dose distribution, the depth of measurement went down to 10cm. The couch was simulated in the Eclipse treatment planning system and the related point dose was calculated with different depths. The CT number of the couch top was adjusted to generate agreement between measurement and simulation. At a 2mm depth, the surface dose increased with the decrease of the field size. Comparing with and without the couch top, as field sizes vary from 20cm×20cm to 2cm×2cm, the dose increased from 35% to 53% of for 6MV, and from 50% to 113% for 18MV. At 0mm depth, the dose difference was most significant and is at the level of 300%. Angle incident beam dose increase due to couch top varied with complicated dose distribution. Extended Depth Dose measurement shows that couch top effect on dose in build-up region extends to depths of 1cm for 6MV and 2cm for 18MV. An appropriate CT number setting of the couch top is between -200HU to -300HU. The couch simulation in Eclipse displays better dosimetric accuracy in couch contacted skin dose. However, calculation factors such as surface definition, heterogeneity, calculation resolution and algorithm also need extra consideration.


Multiscale color invariants based on the human visual system.
This paper proposes a new representation for color texture using a set of multiscale illuminant invariant features. The approach was specifically developed to investigate the feasibility of using machine vision to automatically monitor populations of animal species in ecologically sensitive regions, such as the Amazon Forest. The approach uses a combination of Finlayson's (1994) color angle idea and Gabor multichannel filters and was inspired by the multichannel model of the human visual system (HVS). Using a database of color textures from three species of Amazonian monkey, and also a previously published reference database of color regions, we show that the approach performs better than methods based on color angles or Gabor filters alone. The Monkey database was compiled from texture segments extracted from a video of the Amazon Forest using a spatio-temporal segmentation algorithm. The approach is evaluated by applying two different classification tests in order to measure the quality of the recognition features root mean square (RMS) analysis and receiver operating characteristic (ROC) analysis.


Obesity, increased linear growth, and risk of type 1 diabetes in children.
The purpose of the present study was to evaluate the effect of obesity and linear growth on the risk of developing type 1 diabetes in children. The study population consists of all diabetic children <15 years of age diagnosed from September 1986 to April 1989 in Finland and their birth date- and sex-matched population-based control subjects. Growth data were obtained from well-baby clinics and school health care units for 586 diabetic and 571 control subjects, resulting in a total of 18,823 paired weight-height observations. Both boys and girls who developed type 1 diabetes were heavier and taller throughout childhood than control children. A 10% unit increment in relative weight was associated with a 50-60% increase in the risk of type 1 diabetes before 3 years of age and a 20-40% increase from 3 to 10 years of age. The increase in risk of type 1 diabetes for 1 SD score increment in relative height was 20-30%. Obesity (relative weight > 120%) after 3 years of age was associated with a more than twofold risk of developing type 1 diabetes. The present observation that obesity and rapid linear growth are risk factors for type 1 diabetes in children indicates that the increase in the prevalence of obesity and secular growth that has occurred in most industrialized countries over the last decades may be involved in the increase in type 1 diabetes incidence simultaneously observed in many countries.


A systematic review of randomized controlled trials examining the effectiveness of saffron (Crocus sativus L.) on psychological and behavioral outcomes.
Throughout the past three decades, increased scientific attention has been given to examining saffron's (Crocus sativus L.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. The purpose of this systematic review is to examine and categorize the current state of scientific evidence from randomized controlled trials (RCTs) regarding the efficacy of saffron on psychological/behavioral outcomes. Electronic and non-electronic systematic searches were conducted to identify all relevant human clinical research on saffron. The search strategy was extensive and was designed according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)." Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome. The methodological quality of all included studies was independently evaluated by two reviewers using the Jadad score. Mean scores and P-values of measures were compared both inter- and intra-study for each parameter (i.e., depression). Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n=6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n=4), and weight loss/snacking behaviors (n=1). The data from these studies support the efficacy of saffron as compared to placebo in improving the following conditions: depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition, saffron use was also effective in reducing excessive snacking behavior. Findings from initial clinical trials suggest that saffron may improve the symptoms and the effects of depression, premenstrual syndrome, sexual dysfunction and infertility, and excessive snacking behaviors. Larger multi-site clinical trials are needed to extend these preliminary findings.


Phylogenetic comparison of the methanogenic communities from an acidic, oligotrophic fen and an anaerobic digester treating municipal wastewater sludge.
Methanogens play a critical role in the decomposition of organics under anaerobic conditions. The methanogenic consortia in saturated wetland soils are often subjected to large temperature fluctuations and acidic conditions, imposing a selective pressure for psychro- and acidotolerant community members; however, methanogenic communities in engineered digesters are frequently maintained within a narrow range of mesophilic and circumneutral conditions to retain system stability. To investigate the hypothesis that these two disparate environments have distinct methanogenic communities, the methanogens in an oligotrophic acidic fen and a mesophilic anaerobic digester treating municipal wastewater sludge were characterized by creating clone libraries for the 16S rRNA and methyl coenzyme M reductase alpha subunit (mcrA) genes. A quantitative framework was developed to assess the differences between these two communities by calculating the average sequence similarity for 16S rRNA genes and mcrA within a genus and family using sequences of isolated and characterized methanogens within the approved methanogen taxonomy. The average sequence similarities for 16S rRNA genes within a genus and family were 96.0 and 93.5%, respectively, and the average sequence similarities for mcrA within a genus and family were 88.9 and 79%, respectively. The clone libraries of the bog and digester environments showed no overlap at the species level and almost no overlap at the family level. Both libraries were dominated by clones related to uncultured methanogen groups within the Methanomicrobiales, although members of the Methanosarcinales and Methanobacteriales were also found in both libraries. Diversity indices for the 16S rRNA gene library of the bog and both mcrA libraries were similar, but these indices indicated much lower diversity in the 16S digester library than in the other three libraries.


Effects of Korean red ginseng extract on behavior in children with symptoms of inattention and hyperactivity/impulsivity: a double-blind randomized placebo-controlled trial.
Abstract Objective: There is evidence that Korean red ginseng (KRG) can reduce the production of the adrenal corticosteroids, cortisol, and dehydroepiandrosterone (DHEA), and thus may be a viable treatment for attention-deficit/hyperactivity disorder (ADHD). The present randomized double-blind placebo-controlled clinical trial tested the effect of KRG on children with ADHD symptoms. Subjects 6-15 years, who satisfied the inclusion criteria and had ADHD symptoms, were randomized into a KRG group (n=33) or a control group (n=37). The KRG group received one pouch of KRG (1g KRG extract/pouch) twice a day, and the control group received one pouch of placebo twice a day. At the 8 week point, the primary outcomes were the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for inattention and hyperactivity scale scores, which were measured at baseline and 8 weeks after starting treatment. Secondary outcomes were quantitative electroencephalography theta/beta ratio (QEEG TBR) (measured at baseline and week 8) and salivary cortisol and DHEA levels (measured at baseline and at 4 and 8 weeks). The baseline characteristics of the KRG and control groups were not statistically different. The mean ages of the KRG and control groups were 10.94±2.26 and 10.86±2.41, respectively. The KRG group had significantly decreased inattention/hyperactivity scores compared with the control group at week 8 (least squared means of the differences in inattention adjusted for baseline scores: -2.25 vs. -1.24, p=0.048; hyperactivity: -1.53 vs. -0.61, p=0.047). The KRG group had significantly decreased QEEG TBR compared with the control group (least squared means of the differences: -0.94 vs. -0.14, p=0.001). However, neither the KRG group nor the control group exhibited significant differences in salivary cortisol or DHEA levels at week 8 compared with the baseline levels. No serious adverse events were reported in either group. These results suggest that KRG extract may be an effective and safe alternative treatment for children with inattention and hyperactivity/impulsivity symptoms. Further studies to investigate the efficacy and safety of KRG are warranted.


A study of clinical characteristicsof mediastinal mass.
Mediastinal tumours are uncommon lesions encountered in clinical practice. There has been a significant increase in the incidence of malignant mediastinal tumours over the past four decades. The presentation varies from asymptomatic lesions detected incidentally on imaging to severe life threatening presentations. The study was conducted to assess the clinical characteristics, types, treatment modalities and outcome of mediastinal masses. In this two year prospective study, a total of 35 cases with or without symptoms of mediastinal mass, confirmed by Computed Tomography (CT) imaging were included. The results were expressed as percentages or proportions. Maximum numbers of patients (25.71%) were seen in the 3(rd) decade and majority (94.3%) was symptomatic at presentation. Malignant lesions (68.57%) were more common than benign (31.43%) and lymphoma was the commonest malignant tumour (50%). Mediastinal widening on chest X-ray was seen in 27 cases (77.14%), pleural effusion and lung mass in 5 cases each (14.29%). On CT imaging and sub-classification, anterior mediastinum was the commonest compartment involved (42.86%). Mediastinal masses are usually symptomatic at presentation. Majority of the masses were malignant lesions and the symptoms of mediastinal obstruction was significantly higher in malignant lesions and anterior mediastinal masses. Lymphoma was the most frequent primary mediastinal mass and thymoma constituted the commonest benign anterior mediastinal tumour.


Genetic variation in the dopamine D4 receptor (DRD4) gene and smoking cessation: follow-up of a randomised clinical trial of transdermal nicotine patch.
Smokers of European ancestry (n=720) who participated in a double-blind, randomised, placebo-controlled trial of transdermal nicotine replacement therapy, were genotyped for two functional polymorphisms (variable number of tandem repeats (VNTR) and a C to T transition at position -521 (C-521T)) in the dopamine D4 receptor gene (DRD4) gene. Logistic regression models of abstinence at 12- and 26-week follow-ups were carried out separately for each polymorphism. For the DRD4 VNTR models, the main effect of treatment was significant at both 12-week (P=0.001) and 26-week (P=0.006) follow-ups, indicating an increased likelihood of successful cessation on active nicotine replacement therapy transdermal patch relative to placebo. The main effect of DRD4 VNTR genotype was associated with abstinence at 12-week follow-up (P=0.034), with possession of one or more copies of the long allele associated with reduced likelihood of cessation (17 vs 23%), but this effect was not observed at 26-week follow-up. For the DRD4 C-521T models, no main effect or interaction terms involving genotype were retained in the models at either 12- or 26-week follow-up. These data are consistent with observations from studies of the DRD2 gene that genetic variants related to relatively decreased dopaminergic tone in the mesocorticolimbic system are associated with increased risk for relapse to smoking following a cessation attempt.


The sleep of children with attention deficit hyperactivity disorder on and off methylphenidate: a matched case-control study.
In the present study, we assessed the effects of regular use of methylphenidate medication in children diagnosed with attention deficit hyperactivity disorder (ADHD) on sleep timing, duration and sleep architecture. Twenty-seven children aged 6-12 years meeting diagnostic criteria for Diagnostic and Statistical Manual version IV ADHD and 27 control children matched for age (+/-3 months) and gender. Two nights of standard polysomnographic (PSG) recordings were conducted. ADHD children were allocated randomly to an on- or 48 h off-methylphenidate protocol for first or second recordings. Control children's recordings were matched for night, but no medication was used. Mixed modelling was employed in the analyses so that the full data set was used to determine the degree of medication effects. Methylphenidate in ADHD children prolonged sleep onset by an average of 29 min [confidence interval (CI) 11.6, 46.7], reduced sleep efficiency by 6.5% (CI 2.6, 10.3) and shortened sleep by 1.2 h (CI 0.65, 1.9). Arousal indices were preserved. Relative amounts of stages 1, 2 and slow wave sleep were unchanged by medication. Rapid eye movement sleep was reduced (-2.4%) on the medication night, an effect that became non-significant when control data were incorporated in the analyses. PSG data from ADHD children off-medication were similar to control data. Our findings suggest that methylphenidate reduces sleep quantity but does not alter sleep architecture in children diagnosed with ADHD. An adequate amount of sleep is integral to good daytime functioning, thus the sleep side effects of methylphenidate may affect adversely the daytime symptoms the drug is targeted to control.


Use of streptococcal protein G in obtaining crystals of an antibody Fab fragment in complex with a meningococcal antigen.
Crystals have been obtained of an antibody Fab fragment grown in the presence of a single domain from streptococcal protein G and a ten amino-acid peptide corresponding to the P1.7 serosubtype antigen from the human pathogen Neisseria meningitidis. Crystal trials using the Fab fragment and peptide antigen alone were unsuccessful, but the inclusion of a protein G domain provided an additional variable that generated suitable crystals. Crystals are in space group P21 with unit-cell parameters a = 43.60, b = 63.42, c = 89.63 A, beta = 98.58 degrees and a data set has been collected to 2.9 A resolution using synchrotron radiation. The inclusion of protein G is likely to be of general utility for the crystallization of Fab-antigen complexes.


A Scoping Review of the Involvement of Children's Communication Partners in Aided Augmentative and Alternative Communication Modeling Interventions.
Purpose The purpose of this study was to inform practice and research by identifying and synthesizing research on interventions in which natural communication partners implemented aided augmentative and alternative communication (AAC) modeling strategies. Method A scoping review yielded 29 studies. Data were charted related to participant characteristics, intervention characteristics, partner instruction and assessment, and partner perspectives of social validity. Results More than 157 peer and 100 adult communication partners (e.g., parents, special educators, paraprofessionals) implemented aided AAC modeling strategies within included studies. To teach communication partners intervention strategies, researchers frequently reported using (a) oral instruction, (b) modeling, and (c) practice or application opportunities with performance feedback. Partner instruction frequently involved both training and concurrent support (e.g., coaching, facilitation, consultation, follow-up support). Conclusion Findings from this review inform the design and delivery of aided AAC modeling interventions by children's natural communication partners. Findings also highlight important avenues for enhancing the rigor of future research on interventions involving aided AAC modeling, including the quality of reporting and application of principles from implementation science. Supplemental Material https://doi.org/10.23641/asha.8038505.


Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling.
Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. General population and genitourinary medicine clinic attenders. Heterosexual women and men. Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). Population prevalence; index case reinfection; and partners treated per index case. Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, >10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. The National Institute for Health Research Health Technology Assessment programme.


In vivo profiling reveals immunomodulatory effects of sorafenib and dacarbazine on melanoma.
Sorafenib is a multi-kinase inhibitor used alone or in combination with dacarbazine to treat metastasized melanoma. Our study investigated the relationship between metabolic response assessed by PET-CT and global transcriptome changes during sorafenib and dacarbazine therapy in patients with advanced melanoma. We conducted an open-label, investigator-initiated study that enrolled 13 sorafenib-naïve Stage IV melanoma patients, whose metastases were accessible for repeated biopsies. Treatment regimen included orally administered sorafenib and intravenous dacarbazine. Biopsies of skin or superficial lymph node metastases were taken before treatment (baseline), during sorafenib and after dacarbazine therapy and used for transcriptional profiling and validation experiments. Serum samples were evaluated for cytokine production. Metabolic response to therapy was observed in 45.5% of patients. The study drugs were well tolerated. We observed a clear upregulation of interferon (IFN)-stimulated immune response genes in profiled metastases. The IFNγ-induced gene signature seemed to be enhanced after addition of dacarbazine to sorafenib. Serum IFNγ also increased during therapy, particularly after addition of dacarbazine. Induction of IFNγ stimulated genes correlating with increased serum IFNγ was predictive of better clinical outcome and responders who had significantly higher serum IFNγ levels lived longer. Our data reveal in situ changes in melanoma metastases during treatment with sorafenib and dacarbazine and suggest an additional mechanism of action through immunomodulation.


BRCA1 and BRCA2 mutation analysis in 86 early onset breast/ovarian cancer patients.
Eighty-six women fulfilling specific selection criteria were studied for germline mutations in two breast cancer susceptibility genes, BRCA1 and BRCA2, using the protein truncation test (PTT). Nine germline mutations were identified, six in BRCA1 and three in BRCA2. Of the six BRCA1 mutations, three have previously been described and three are new, and for BRCA2, one is a new mutation and the other two appear to occur at a site that has been described several times. Four kindreds were breast cancer families, one a breast/ovarian cancer family, and the sixth an ovarian cancer family. The three kindreds with BRCA2 mutations were classified as one breast/ovarian cancer family, one breast cancer family, and one family which harboured one early onset breast cancer patient and two melanoma patients. The mutations in BRCA1 were either insertions, deletions, or transitions which all resulted in a premature stop codon. Mutations in BRCA2 were all frameshift mutations as a result of either 2 or 4 bp deletions. Two BRCA2 mutations were identical, suggesting a Swiss founder effect which was confirmed by haplotype sharing. The 10% mutation detection rate is compatible with the relaxed criteria used for patient selection. Considering the relative ease with which coding sequences can be screened by PTT, this assay is useful as a first screen for BRCA1 and BRCA2 mutations.


Neural mechanisms underlying adaptive actions after slips.
An increase in cognitive control has been systematically observed in responses produced immediately after the commission of an error. Such responses show a delay in reaction time (post-error slowing) and an increase in accuracy. To characterize the neurophysiological mechanism involved in the adaptation of cognitive control, we examined oscillatory electrical brain activity by electroencephalogram and its corresponding neural network by event-related functional magnetic resonance imaging in three experiments. We identified a new oscillatory theta-beta component related to the degree of post-error slowing in the correct responses following an erroneous trial. Additionally, we found that the activity of the right dorsolateral prefrontal cortex, the right inferior frontal cortex, and the right superior frontal cortex was correlated with the degree of caution shown in the trial following the commission of an error. Given the overlap between this brain network and the regions activated by the need to inhibit motor responses in a stop-signal manipulation, we conclude that the increase in cognitive control observed after the commission of an error is implemented through the participation of an inhibitory mechanism.


Plague outbreak in Libya, 2009, unrelated to plague in Algeria.
After 25 years of no cases of plague, this disease recurred near Tobruk, Libya, in 2009. An epidemiologic investigation identified 5 confirmed cases. We determined ribotypes, Not1 restriction profiles, and IS100 and IS1541 hybridization patterns of strains isolated during this outbreak. We also analyzed strains isolated during the 2003 plague epidemic in Algeria to determine whether there were epidemiologic links between the 2 events. Our results demonstrate unambiguously that neighboring but independent plague foci coexist in Algeria and Libya. They also indicate that these outbreaks were most likely caused by reactivation of organisms in local or regional foci believed to be dormant (Libya) or extinct (Algeria) for decades, rather than by recent importation of Yersinia pestis from distant foci. Environmental factors favorable for plague reemergence might exist in this area and lead to reactivation of organisms in other ancient foci.


Underrepresented Minorities are Underrepresented Among General Surgery Applicants Selected to Interview.
Diversity is an ill-defined entity in general surgery training. The Accreditation Council for Graduate Medical Education recently proposed new common program requirements including verbiage requiring diversity in residency. "Recruiting" for diversity can be challenging within the constraints of geographic preference, type of program, and applicant qualifications. In addition, the Match process adds further uncertainty. We sought to study the self-identified racial/ethnic distribution of general surgery applicants to better ascertain the characteristics of underrepresented minorities (URM) within the general surgery applicant pool. Program-specific data from the Electronic Residency Application Service was collated for the 2018 medical student application cycle. Data were abstracted for all participating programs' applicants and those selected to interview. Applicants who did not enter a self-identified race/ethnicity were excluded from analysis. URM were defined as those identifying as Black/African American, Hispanic/Latino/of Spanish origin, American Indian/Alaskan Native, or Native Hawaiian/Pacific Islander-Samoan. Appropriate statistical analyses were accomplished. Ten general surgery residency programs-5 independent programs and 5 university programs. Residency applicants to the participating general surgery residency programs. Ten surgery residency programs received 10,312 applications from 3192 unique applicants. Seven hundred and seventy-eight applications did not include a self-identified race/ethnicity and were excluded from analysis. The racial/ethnic makeup of applicants in this study cohort was similar to that from 2017 to 2018 Electronic Residency Application Service data of 4262 total applicants to categorical general surgery. Programs received a median of 1085 (range: 485-1264) applications each and altogether selected 617 unique applicants for interviews. Overall, 2148 applicants graduated from US medical schools, and of those, 595 (28%) were offered interviews. The mean age of applicants was 28.8 ± 3.8 years and 1316 (41%) were female. Hispanic/Latino/of Spanish origin, Black, and American Indian/Alaskan Native/Hawaiian/Pacific Islander-Samoan applicants constituted 12%, 8%, and 1% of total applicants, but only 8%, 6%, and 1% of those selected for interview. Overall, 29% of applicants had United States Medical Licensing Examination (USMLE) Step 1 scores ≤220; 37 (6%) of those selected for interviews had a USMLE Step 1 score of ≤220. A higher proportion of URM applicants had USMLE scores ≤220 compared to White and Asian applicants. Non-white self-identification was a significant independent predictor of a lower likelihood of interview selection. Female gender, USMLE Step 1 score >220, and graduating from a US medical school were associated with an increased likelihood of being selected to interview. URM applicants represented a disproportionately smaller percentage of applicants selected for interview. USMLE Step 1 scores were lower among the URM applicants. Training programs that use discreet USMLE cutoffs are likely excluding URM at a higher rate than their non-URM applicants. Attempts to recruit racially/ethnically diverse trainees should include program-level analysis to determine disparities and a focused strategy to interview applicants who might be overlooked by conventional screening tools.


Making decisions about delirium: a qualitative comparison of decision making between nurses working in palliative care, aged care, aged care psychiatry, and oncology.
Delirium has a significant impact on nursing practice from diagnosis and management, with under-detection and variable management of delirium being international problems. This study aimed to explore nurses' assessment and management of delirium when caring for people with cancer, the elderly or older people requiring psychiatric care in the inpatient setting. Participants in this qualitative study were nurses working in Australian public hospital inpatient dedicated units in palliative care, aged care (geriatrics), aged care (geriatric) psychiatry and oncology. Semi-structured interviews were used to explore nurses' views about specific areas of delirium assessment and management. Purposive sampling was used and interviews conducted until thematic saturation reached. A thematic content analysis was performed from a grounded theory perspective. A total of 40 participants were included in the study. The analysis revealed four broad analytical themes: (1) superficial recognition and understanding of the operational definition of delirium or recognition of delirium as a syndrome; (2) nursing assessment: investigative versus a problem solving approach; (3) management: maintaining dignity and minimizing chaos; and (4) distress and the effect on others. Nurses have limited knowledge of the features of delirium regardless of their specialty discipline. Delirium was uniformly identified as a highly distressing experience for patients, families and staff alike. The majority of nurses had a superficial understanding of delirium management, and adopted a task-orientated approach aimed at addressing the more noticeable problems. These findings have implications for both education and knowledge translation. Innovative approaches are needed to align health professional behaviours with best evidence delirium care.


On the relationship between radiance and irradiance: determining the illumination from images of a convex Lambertian object.
We present a theoretical analysis of the relationship between incoming radiance and irradiance. Specifically, we address the question of whether it is possible to compute the incident radiance from knowledge of the irradiance at all surface orientations. This is a fundamental question in computer vision and inverse radiative transfer. We show that the irradiance can be viewed as a simple convolution of the incident illumination, i.e., radiance and a clamped cosine transfer function. Estimating the radiance can then be seen as a deconvolution operation. We derive a simple closed-form formula for the irradiance in terms of spherical harmonic coefficients of the incident illumination and demonstrate that the odd-order modes of the lighting with order greater than 1 are completely annihilated. Therefore these components cannot be estimated from the irradiance, contradicting a theorem that is due to Preisendorfer. A practical realization of the radiance-from-irradiance problem is the estimation of the lighting from images of a homogeneous convex curved Lambertian surface of known geometry under distant illumination, since a Lambertian object reflects light equally in all directions proportional to the irradiance. We briefly discuss practical and physical considerations and describe a simple experimental test to verify our theoretical results.


Long-term potentiation: outstanding questions and attempted synthesis.
This article attempts an overview of the mechanism of NMDAR-dependent long-term potentiation (LTP) and its role in hippocampal networks. Efforts are made to integrate information, often in speculative ways, and to identify unresolved issues about the induction, expression and molecular storage processes. The pre/post debate about LTP expression has been particularly difficult to resolve. The following hypothesis attempts to reconcile the available physiological evidence as well as anatomical evidence that LTP increases synapse size. It is proposed that synapses are composed of a variable number of trans-synaptic modules, each having presynaptic release sites and a postsynaptic structure that can be AMPAfied by the addition of a hyperslot assembly that anchors 10-20 AMPA channels. According to a newly developed view of transmission, the quantal response is generated by AMPA channels near the site of vesicle release and so will depend on whether the module where release occurs has been AMPAfied. LTP expression may involve two structurally mediated processes: (i) the AMPAfication of existing modules by addition of hyperslot assemblies: this is a purely postsynaptic process and produces an increase in the probability of an AMPA response, with no change in the NMDA component; and (ii) the addition of new modules: this is a structurally coordinated pre/post process that leads to LTP-induced synapse enlargement and potentiation of the NMDA component owing to an increase in the number of release sites (the number of NMDA channels is assumed to be fixed). The protocol used for LTP induction appears to affect the proportion of these two processes; pairing protocols that involve low-frequency presynaptic stimulation induce only AMPAfication, making LTP purely postsynaptic, whereas high-frequency stimulation evokes both processes, giving rise to a presynaptic component. This model is capable of reconciling much of the seemingly contradictory evidence in the pre/post debate. The structural nature of the postulated changes is relevant to a second debate: whether a CaMKII switch or protein-dependent structural change is the molecular memory mechanism. A possible reconciliation is that a reversible CaMKII switch controls the construction of modules and hyperslot assemblies from newly synthesized proteins.


Building inclusive community: a challenge for occupational therapy. 1994 Eleanor Clarke Slagle Lecture.
Occupational therapy was founded on values of choice, relevance, and active participation in meaningful occupations. To assure choice in daily living, learning, work, and play for persons with disabilities or significant health issues, occupational therapy practitioners are challenged to gain increased understanding of the unique culture and community of each person and family with whom they work; create opportunities for these persons to develop their capabilities in community settings of their choice; promote more interactive models of practice in which the practitioner affects the arrangements between the person and society; work with communities to welcome the gifts of diversity; and develop skill in analyzing environments and facilitating environmental interaction. The environment category of the spatiotemporal adaptation theory is expanded and a communication model for collaboration in building individual community is proposed as means for addressing the challenges.


Genetic typing of HLA class II genes in Swedish populations: application to forensic analysis.
In an attempt to determine the value of DNA based typing of HLA class II loci to forensic analysis, allele and genotype frequencies at DQA1, DQB1, DPB1, and DRB1 were determined in samples from two Swedish populations using hybridization with sequence specific oligonucleotides to PCR amplified DNA. Significant allele frequency differences were observed at the DQB1 and DRB1 loci between the two populations, as well as between one of the Swedish and a Norwegian population. The average heterozygosity varies between 0.74 to 0.91 and the power of discrimination between 0.90 to 0.98, with the highest values obtained for the DRB1 locus. The probability of genotype identity by chance differs on average 2% between the populations. When applied to a paternity case with one parent deceased and a criminal case, typing of class II loci proved in both cases informative. Analyses of DR and DQ genes does not increase the power of discrimination, due to strong linkage, but offers through the reconstruction of putative haplotypes an internal control for the consistency of the typing results at several loci. Typing of the DRB1 and DPB1 loci was found to result in an approximate combined average probability of genotype identity by chance of one in a thousand.


An evaluation of an acuity system as it applies to a cardiac catheterization laboratory.
Patient care using patient volume rather than acuity has been a long-standing problem in a cardiac catheterization laboratory in a central New Jersey Medical Center. The current pattern of staffing results in some of the nursing staff becoming unproductive from a patient care perspective. This recently has become a concern of the Vice President of Nursing who has the unpopular task of consolidating nursing positions. There is a very effective acuity measurement system, the Medicus Acuity System, in place for the various inpatient areas. This system also exists in the Emergency Department and is called EMERGE. The system collects and objectively weighs information regarding severity of patient needs or acuity. These data are collected daily and provide unit managers with information regarding hours of direct nursing care on their particular units. The information over time shows trends in direct care hours and allows these managers to target the average patient population. The system gives insight into units that require more and less nursing hours by hour of the day, day of the week, and month of the year. This makes overall housewide use of nursing personnel more patient-care appropriate and more financially sound, for example, in the summer months when acuity is shown to be higher. In today's managed care environment this author believes the practice of staffing units based on bed occupancy is now regarded as antiquated, inefficient, and impractical. This study investigated a modified version of the EMERGE tool and its ability to capture patient acuity as it relates to staffing in the cardiovascular laboratory (CVL). During the 5 days of data collection, 87 patients were cared for in the CVL. The modified EMERGE cards were completed on 54 of the 87 patients that week. This represented 62% of that total patient population. Each day data for 60% or more of the patients were entered into the study. The interrater reliability of the data collected was better than 98% each day with overall accuracy being 99.5%. This interrater reliability was based on the findings by the expert panel, who compared two or three (approximately 10%) of the actual nurses' notes to the matching EMERGE cards each day. More than 80% of the 54 patients were classified as Type 3, well above the Type 1 standard patient acuity category for the EMERGE system. Telemetry units with a majority of EMERGE Type 3 patients would require between 50 to 100 minutes of care per visit and would have a significant nursing workload. These units are where the CVL draws most of their patient population. In summary, this study reflects a growing trend in healthcare that requires justification of staffing through the productivity of workers. Acuity tools provide tangible and objective data about daily workload and productivity by measuring patient's needs. As managed care forces hospitals to cutt staff, acuity tools will become more important for evaluating productivity and retaining staff, especially nurses.


A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification.
Base excision repair (BER) proteins act upon a significantly broad spectrum of DNA lesions that result from endogenous and exogenous sources. Multiple sub-pathways of BER (short-path or long-patch) and newly designated DNA repair pathways (e.g., SSBR and NIR) that utilize BER proteins complicate any comprehensive understanding of BER and its role in genome maintenance, chemotherapeutic response, neuro-degeneration, cancer or aging. Herein, we propose a unified model of BER, comprised of three functional processes: Lesion Recognition/Strand Scission, Gap Tailoring and DNA Synthesis/Ligation, each represented by one or more multi-protein complexes and coordinated via the XRCC1/DNA Ligase III and PARP1 scaffold proteins. BER therefore may be represented by a series of repair complexes that assemble at the site of the DNA lesion and mediates repair in a coordinated fashion involving protein-protein interactions that dictate subsequent steps or sub-pathway choice. Complex formation is influenced by post-translational protein modifications that arise from the cellular state or the DNA damage response, providing an increase in specificity and efficiency to the BER pathway. In this review, we have summarized the reported BER protein-protein interactions and protein post-translational modifications and discuss the impact on DNA repair capacity and complex formation.


Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice.
The therapeutic potential of molecular hydrogen (H₂) is emerging in a number of human diseases and in their animal models, including in particular Parkinson's disease (PD). H₂ supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H₂ supplementation does not result in detectable changes in striatal H₂ levels, indicating an indirect effect. Here we show that H₂ supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the β1-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H₂ water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H₂ in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H₂ supplementation has been demonstrated.


Structure of murine and human renal type II Na+-phosphate cotransporter genes (Npt2 and NPT2).
Na+-phosphate (Pi) cotransport across the renal brush border membrane is the rate limiting step in the overall reabsorption of filtered Pi. Murine and human renal-specific cDNAs (NaPi-7 and NaPi-3, respectively) related to this cotransporter activity (type II Na+-Pi cotransporter) have been cloned. We now report the cloning and characterization of the corresponding mouse (Npt2) and human (NPT2) genes. The genes were cloned by screening mouse genomic and human chromosome 5-specific libraries, respectively. Both genes are approximately 16 kb and are comprised of 13 exons and 12 introns, the junctions of which conform to donor and acceptor site consensus sequences. Putative CAAT and TATA boxes are located, respectively, at positions -147 and -40 of the Npt2 gene and -143 and -51 of the NPT2 gene, relative to nucleotide 1 of the corresponding cDNAs. The translation initiation site is within exon 2 of both genes. The first 220 bp of the mouse and human promoter regions exhibit 72% identity. Two transcription start sites (at positions -9 and - 10 with respect to nucleotide 1 of NaPi-7 cDNA) and two polyadenylylation signals were identified in the Npt2 gene by primer extension, 5' and 3' rapid amplification of cDNA ends (RACE). A 484-bp 5' flanking region of the Npt2 gene, comprising the CAAT box, TATA box, and exon 1, was cloned upstream of a luciferase reporter gene; this construct significantly stimulated luciferase gene expression, relative to controls, when transiently transfected into OK cells, a renal cell line expressing type II Na+ -Pi cotransporter activity. The present data provide a basis for detailed analysis of cis and trans elements involved in the regulation of Npt2/NPT2 gene transcription and facilitate screening for mutations in the NPT2 gene in patients with autosomally inherited disorders of renal Pi reabsorption.


Comprehensive survey and classification of homeobox genes in the genome of amphioxus, Branchiostoma floridae.
The homeobox genes comprise a large and diverse gene superfamily, many of which encode transcription factors with pivotal roles in the embryonic development of animals. We searched the assembled draft genome sequence of an amphioxus, Branchiostoma floridae, for genes possessing homeobox sequences. Phylogenetic analysis was used to divide these into gene families and classes. The 133 amphioxus homeobox genes comprise 60 ANTP class genes, 29 PRD genes (excluding Pon and Pax1/9), nine TALE genes, seven POU genes, seven LIM genes, five ZF genes, four CUT genes, four HNF genes, three SINE genes, one CERS gene, one PROS gene, and three unclassified genes. Ten of the 11 homeobox gene classes are less diverse in amphioxus than humans, as a result of gene duplication on the vertebrate lineage. Amphioxus possesses at least one member for all of the 96 homeobox gene families inferred to be present in the common ancestor of chordates, including representatives of the Msxlx, Bari, Abox, Nk7, Ro, and Repo gene families that have been lost from tunicates and vertebrates. We find duplication of several homeobox genes in the cephalochordate lineage (Mnx, Evx, Emx, Vent, Nk1, Nedx, Uncx, Lhx2/9, Hmbox, Pou3, and Irx) and several divergent genes that probably originated by extensive sequence divergence (Hx, Ankx, Lcx, Acut, Atale, Azfh, Ahbx, Muxa, Muxb, Aprd1-6, and Ahnf). The analysis reveals not only the repertoire of amphioxus homeobox genes but also gives insight into the evolution of chordate homeobox genes.


Lab-on-a-chip devices for global health: past studies and future opportunities.
A rapidly emerging field in lab-on-a-chip (LOC) research is the development of devices to improve the health of people in developing countries. In this review, we identify diseases that are most in need of new health technologies, discuss special design criteria for LOC devices to be deployed in a variety of resource-poor settings, and review past research into LOC devices for global health. We focus mainly on diagnostics, the nearest-term application in this field.


Hypoxia causes preservation of labile organic matter and changes seafloor microbial community composition (Black Sea).
Bottom-water oxygen supply is a key factor governing the biogeochemistry and community composition of marine sediments. Whether it also determines carbon burial rates remains controversial. We investigated the effect of varying oxygen concentrations (170 to 0 μM O2) on microbial remineralization of organic matter in seafloor sediments and on community diversity of the northwestern Crimean shelf break. This study shows that 50% more organic matter is preserved in surface sediments exposed to hypoxia compared to oxic bottom waters. Hypoxic conditions inhibit bioturbation and decreased remineralization rates even within short periods of a few days. These conditions led to the accumulation of threefold more phytodetritus pigments within 40 years compared to the oxic zone. Bacterial community structure also differed between oxic, hypoxic, and anoxic zones. Functional groups relevant in the degradation of particulate organic matter, such as Flavobacteriia, Gammaproteobacteria, and Deltaproteobacteria, changed with decreasing oxygenation, and the microbial community of the hypoxic zone took longer to degrade similar amounts of deposited reactive matter. We conclude that hypoxic bottom-water conditions-even on short time scales-substantially increase the preservation potential of organic matter because of the negative effects on benthic fauna and particle mixing and by favoring anaerobic processes, including sulfurization of matter.


Palliative care communication curriculum: what can students learn from an unfolding case?
Limited attention to palliative care communication training is offered to medical students. In this work, we pursued unfolding case responses and what they indicated about student tendencies to use palliative care communication as well as what medical students can learn from their own reflective practice about palliative care. Findings showed an overwhelming trend for students to avoid palliative care communication or inclusion of topics including advance directives, place of care, family support, and dying. Instead, students relied heavily on the SPIKES protocol, communication that was strategically vague and ambiguous, and discussions that centered on specialty care and referral. In reflecting on their own case study responses, students noted an absence of direct communication about prognosis, no coordination of care, late hospice entry, and patient pain resulting from communication inefficacies. Future research should focus on the development of formal and adaptive curriculum structures to address these communication needs.


A Role for Taok2 in Listeria monocytogenes Vacuolar Escape.
The bacterial pathogen Listeria monocytogenes invades host cells, ruptures the internalization vacuole, and reaches the cytosol for replication. A high-content small interfering RNA (siRNA) microscopy screen allowed us to identify epithelial cell factors involved in L. monocytogenes vacuolar rupture, including the serine/threonine kinase Taok2. Kinase activity inhibition using a specific drug validated a role for Taok2 in favoring L. monocytogenes cytoplasmic access. Furthermore, we showed that Taok2 recruitment to L. monocytogenes vacuoles requires the presence of pore-forming toxin listeriolysin O. Overall, our study identified the first set of host factors modulating L. monocytogenes vacuolar rupture and cytoplasmic access in epithelial cells.


The role of functional traits and individual variation in the co-occurrence of Ficus species.
The processes that structure assemblages of species in hyper-diverse genera, such as Ficus (Moraceae), are not well understood. Functional diversity of co-occurring species can reveal evidence for assembly processes; however, intraspecific variation may weaken species-level patterns. We studied whether functional and phylogenetic diversity of Ficus species indicated the effects of spatial variation in filters associated with topography or niche partitioning related to resource use and biotic interactions. We also asked whether individual trait patterns supported species-level patterns. We studied six traits (leaf area, succulence, specific leaf area [SLA], maximum diameter breast high [dbh], fruit size, and latex exudation) for 22 Ficus species and 335 individuals > or = 10 cm dbh on a 20-ha forest plot in China. We found that higher elevation was correlated to changes in mean and reduced diversity of five traits, possibly due to frequent disturbances at higher elevations that favored fast-growing, poorly defended species with high SLA. Maximum dbh showed phylogenetic conservatism but high diversity among co-occurring species, suggesting adult stature is an important axis of within-quadrat niche partitioning. At the individual level, trait patterns were qualitatively consistent but were stronger than species-level patterns, especially for the leaf traits with the greatest intraspecific variation (SLA and succulence). Individual-level SLA exhibited the strongest evidence for both traits among and within-quadrat niche partitioning and indicated elevational filtering. Local niche partitioning and elevational filtering likely play an important role in maintaining species and functional diversity in the most speciose genus at our study site. Our results highlight the importance of individual variation, as it may reveal otherwise obscured niche effects.


Hyperspectral molecular imaging of multiple receptors using immunolabeled plasmonic nanoparticles.
This work presents simultaneous imaging and detection of three different cell receptors using three types of plasmonic nanoparticles (NPs). The size, shape, and composition-dependent scattering profiles of these NPs allow for a system of multiple distinct molecular markers using a single optical source. With this goal in mind, tags consisting of anti-epidermal growth factor receptor gold nanorods, anti-insulin-like growth factor 1-R silver nanospheres, and human epidermal growth factor receptor 2Ab gold nanospheres were developed to monitor the expression of receptors commonly overexpressed by cancer cells. These labels were chosen because they scatter strongly in distinct spectral windows. A hyperspectral darkfield microspectroscopy system was developed to record the scattering spectra of cells labeled with these molecular tags. Simultaneous monitoring of multiple tags may lead to applications such as profiling of cell line immunophenotype and investigation of receptor signaling pathways. Single, dual, and triple tag experiments were performed to analyze NP tag specificity as well as their interactions. Distinct resonance peaks were observed in these studies, showing the ability to characterize cell lines using conjugated NPs. However, interpreting shifts in these peaks due to changes in a cellular dielectric environment may be complicated by plasmon coupling between NPs bound to proximal receptors and other coupling mechanisms due to the receptors themselves.


Household and preschooler vitamin A consumption in southwestern Kenya.
This study examined the effects of an income-generating policy to expand the commercialization of subsistence agriculture in southwestern Kenya on household and preschooler macro- and micronutrient consumption. A representative sample of 617 household was included, and all preschoolers under the age of 6 y (1677) residing in these households were included in the study. Results of this analysis indicate that although increases in household income do result in improved household level vitamin A consumption, increases in household income are not significantly associated with the intake of dietary vitamin A by preschoolers. The analysis suggests that although increases in household income have some very positive effects on household food security and household micronutrient consumption, other community-based health, sanitation and nutrition interventions are needed to address the dietary needs of individuals within the household.


Molecular Characterization of Haemaphysalis Species and a Molecular Genetic Key for the Identification of Haemaphysalis of North America.
Haemaphysalis longicornis (Acari: Ixodidae), the Asian longhorned tick, is native to East Asia, but has become established in Australia and New Zealand, and more recently in the United States. In North America, there are other native Haemaphysalis species that share similar morphological characteristics and can be difficult to identify if the specimen is damaged. The goal of this study was to develop a cost-effective and rapid molecular diagnostic assay to differentiate between exotic and native Haemaphysalis species to aid in ongoing surveillance of H. longicornis within the United States and help prevent misidentification. We demonstrated that restriction fragment length polymorphisms (RFLPs) targeting the 16S ribosomal RNA and the cytochrome c oxidase subunit I (COI) can be used to differentiate H. longicornis from the other Haemaphysalis species found in North America. Furthermore, we show that this RFLP assay can be applied to Haemaphysalis species endemic to other regions of the world for the rapid identification of damaged specimens. The work presented in this study can serve as the foundation for region specific PCR-RFLP keys for Haemaphysalis and other tick species and can be further applied to other morphometrically challenging taxa.


Is the stock market efficient?
A stock market is said to be efficient if it accurately reflects all relevant information in determining security prices. Critics have asserted that share prices are far too volatile to be explained by changes in objective economic events-the October 1987 crash being a case in point. Although the evidence is not unambiguous, reports of the death of the efficient market hypothesis appear premature.


Effect of Electromechanical Stimulation on the Maturation of Myotubes on Aligned Electrospun Fibers.
Tissue engineering may provide an alternative to cell injection as a therapeutic solution for myocardial infarction. A tissue-engineered muscle patch may offer better host integration and higher functional performance. This study examined the differentiation of skeletal myoblasts on aligned electrospun polyurethane (PU) fibers and in the presence of electromechanical stimulation. Skeletal myoblasts cultured on aligned PU fibers showed more pronounced elongation, better alignment, higher level of transient receptor potential cation channel-1 (TRPC-1) expression, upregulation of contractile proteins and higher percentage of striated myotubes compared to those cultured on random PU fibers and film. The resulting tissue constructs generated tetanus forces of 1.1 mN with a 10-ms time to tetanus. Additional mechanical, electrical, or synchronized electromechanical stimuli applied to myoblasts cultured on PU fibers increased the percentage of striated myotubes from 70 to 85% under optimal stimulation conditions, which was accompanied by an upregulation of contractile proteins such as α-actinin and myosin heavy chain. In describing how electromechanical cues can be combined with topographical cue, this study helped move towards the goal of generating a biomimetic microenvironment for engineering of functional skeletal muscle.


Azidoatrazine: photoaffinity label for the site of triazine herbicide action in chloroplasts.
Binding of the 4-azido analog of the herbicide atrazine to pea chloroplast membranes was compared with that of atrazine. When [(14)C]azidoatrazine was treated with 300-nanometer ultraviolet light in situ, reversibility of binding was lost in proportion to the duration of irradiation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of chloroplast membranes irradiated in the presence of [(l4)C]-azidoatrazine indicated radioactivity in only one region, corresponding to a protein with a molecular weight of approximately 32,000. Azidoatrazine is a photoaffinity reagent for the triazine binding site in chloroplasts and serves as a label to identify this site, which may be the apoprotein of the secondary electron acceptor in photosystem II.


Real-time GPU surface curvature estimation on deforming meshes and volumetric data sets.
Surface curvature is used in a number of areas in computer graphics, including texture synthesis and shape representation, mesh simplification, surface modeling, and nonphotorealistic line drawing. Most real-time applications must estimate curvature on a triangular mesh. This estimation has been limited to CPU algorithms, forcing object geometry to reside in main memory. However, as more computational work is done directly on the GPU, it is increasingly common for object geometry to exist only in GPU memory. Examples include vertex skinned animations and isosurfaces from GPU-based surface reconstruction algorithms. For static models, curvature can be precomputed and CPU algorithms are a reasonable choice. For deforming models where the geometry only resides on the GPU, transferring the deformed mesh back to the CPU limits performance. We introduce a GPU algorithm for estimating curvature in real time on arbitrary triangular meshes. We demonstrate our algorithm with curvature-based NPR feature lines and a curvature-based approximation for an ambient occlusion. We show curvature computation on volumetric data sets with a GPU isosurface extraction algorithm and vertex-skinned animations. We present a graphics pipeline and CUDA implementation. Our curvature estimation is up to ~18x faster than a multithreaded CPU benchmark.


Acceptance and commitment therapy versus cognitive behavioral therapy in the treatment of substance use disorder with incarcerated women.
This randomized controlled study compared acceptance and commitment therapy (ACT), cognitive-behavioral therapy (CBT), and a control group. The participants were 50 incarcerated women diagnosed with current substance use disorder. Two psychologists carried out pre- and posttreatment assessment and a 6-month follow-up assessment using the following instruments: Anxiety Sensitivity Index, Addiction Severity Index-6, Mini International Neuropsychiatric Interview, and Acceptance and Action Questionnaire. The study shows that the women who received treatment benefited differentially from the interventions. At posttreatment, CBT was more effective than ACT in reducing anxiety sensitivity; however, at follow-up, ACT was more effective than CBT in reducing drug use (43.8 vs. 26.7%, respectively) and improving mental health (26.4% vs. 19.4%, respectively). ACT may be an alternative to CBT for treatment of drug abuse and associated mental disorders. In fact, at long-term, ACT may be more appropriate than CBT for incarcerated women who present serious problems.


Economic, Health and Physical Impacts of COVID-19 Pandemic in Sub-Saharan African Regions: A Cross Sectional Survey.
The key preventive measures adopted to minimise the spread of the coronavirus disease (COVID-19) had significant health, economic and physical impacts mostly in developing countries. This study evaluated the health, economic and physical impacts of COVID-19 lockdown measures among sub-Saharan African (SSA) population and associated demographic variations. A total of 1970 respondents took part in this web-based cross-sectional survey during the mandatory lockdown period in most SSA. The dependent variables were health (COVID-19 infection, hospitalisation), socioeconomic (lost job, closed down business) and physical impacts (separated from family) of COVID-19. Univariate and bivariate logistic regression analyses were used to explore the factors associated with each of the dependent variables by the four sub-regions (Southern, Western, Central and East Africa). The respondents were aged 34.1 ± 11.5 years (range: 18-75 years) and mostly men (1099, 55%). 25.9% (n = 511) reported an impact of COVID-19 pandemic with significant regional variations (p < 0.0005, higher proportion were East 36.2% and Southern Africans 30.3%) but no gender (p = 0.334) and age group variations (p > 0.05). Among Central African respondents, more men than women lost their businesses (45.7% versus 14.3%, p = 0.002) and contracted COVID-19 infections (40.0% versus 18.2%, p = 0.024) during the study period. Multivariable analysis revealed that respondents from East (adjusted odds ratio [AOR] 1.95, 95% confidence interval [CI]: 1.42-2.69), Southern (AOR 1.46, 95% CI: 1.09-1.96) and Central Africa (AOR 1.47, 95% CI: 1.06-2.03) reported significantly higher impact of COVID-19. Those who reported family separation during the lockdown were more likely to be older participants (39-48 years, AOR 2.48, 95% CI: 1.11-5.57). One in four SSA respondents, mostly East and Southern Africans, were adversely affected by the COVID-19 pandemic during the lockdown. Interventions in high-risk populations are needed to reduce the health, socioeconomic and gender disparities in the impacts of COVID-19.


Determinants for association and guide RNA-directed endonuclease cleavage by purified RNA editing complexes from Trypanosoma brucei.
U-insertion/deletion RNA editing in the single mitochondrion of kinetoplastids, an ancient lineage of eukaryotes, is a unique mRNA maturation process needed for translation. Multisubunit editing complexes recognize many pre-edited mRNA sites and modify them via cycles of three catalytic steps: guide RNA (gRNA)-directed cleavage, insertion or deletion of uridylates at the 3'-terminus of the upstream cleaved piece, and ligation of the two mRNA pieces. While catalytic and many structural protein subunits of these complexes have been identified, the mechanisms and basic determinants of substrate recognition are still poorly understood. This study defined relatively simple single- and double-stranded determinants for association and gRNA-directed cleavage. To this end, we used an electrophoretic mobility shift assay to directly score the association of purified editing complexes with RNA ligands, in parallel with UV photocrosslinking and functional studies. The cleaved strand required a minimal 5' overhang of 12 nt and an approximately 15-bp duplex with gRNA to direct the cleavage site. A second protruding element in either the cleaved or the guide strand was required unless longer duplexes were used. Importantly, the single-stranded RNA requirement for association can be upstream or downstream of the duplex, and the binding and cleavage activities of purified editing complexes could be uncoupled. The current observations together with our previous reports in the context of purified native editing complexes show that the determinants for association, cleavage and full-round editing gradually increase in complexity as these stages progress. The native complexes in these studies contained most, if not all, known core subunits in addition to components of the MRP complex. Finally, we found that the endonuclease KREN1 in purified complexes photocrosslinks with a targeted editing site. A model is proposed whereby one or more RNase III-type endonucleases mediate the initial binding and scrutiny of potential ligands and subsequent catalytic selectivity triggers either insertion or deletion editing enzymes.


Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades.
The emergence of pandemic GII.4 norovirus (NoV) strains has been proposed to occur due to changes in receptor usage and thereby to lead to immune evasion. To address this hypothesis, we measured the ability of human sera collected between 1979 and 2010 to block glycan binding of four pandemic GII.4 noroviruses isolated in the last 4 decades. In total, 268 sera were investigated for 50% blocking titer (BT50) values of virus-like particles (VLPs) against pig gastric mucin (PGM) using 4 VLPs that represent different GII.4 norovirus variants identified between 1987 and 2012. Pre- and postpandemic sera (sera collected before and after isolation of the reference NoV strain) efficiently prevented binding of VLP strains MD145 (1987), Grimsby (1995), and Houston (2002), but not the Sydney (2012) strain, to PGM. No statistically significant difference in virus-blocking titers was observed between pre- and postpandemic sera. Moreover, paired sera showed that blocking titers of ≥160 were maintained over a 6-year period against MD145, Grimsby, and Houston VLPs. Significantly higher serum blocking titers (geometric mean titer [GMT], 1,704) were found among IgA-deficient individuals than among healthy blood donors (GMT, 90.9) (P < 0.0001). The observation that prepandemic sera possess robust blocking capacity for viruses identified decades later suggests a common attachment factor, at least until 2002. Our results indicate that serum IgG possesses antibody-blocking capacity and that blocking titers can be maintained for at least 6 years against 3 decades of pandemic GII.4 NoV.IMPORTANCE Human noroviruses (NoVs) are the major cause of acute gastroenteritis worldwide. Histo-blood group antigens (HBGAs) in saliva and gut recognize NoV and are the proposed ligands that facilitate infection. Polymorphisms in HBGA genes, and in particular a nonsense mutation in FUT2 (G428A), result in resistance to global dominating GII.4 NoV. The emergence of new pandemic GII.4 strains occurs at intervals of several years and is proposed to be attributable to epochal evolution, including amino acid changes and immune evasion. However, it remains unclear whether exposure to a previous pandemic strain stimulates immunity to a pandemic strain identified decades later. We found that prepandemic sera possess robust virus-blocking capacity against viruses identified several decades later. We also show that serum lacking IgA antibodies is sufficient to block NoV VLP binding to HBGAs. This is essential, considering that 1 in every 600 Caucasian children is IgA deficient.


Training the Unimpaired Arm Improves the Motion of the Impaired Arm and the Sitting Balance in Chronic Stroke Survivors.
Robot-assisted rehabilitation of stroke survivors mainly focuses on the impaired side of the body while the role of the unimpaired side in the recovery after stroke is still controversial. The goal of this study is to investigate the influence on sitting balance and paretic arm functions of a training protocol based on movements of the unimpaired arm. Sixteen chronic stroke survivors underwent nineteen training sessions, in which they performed active movements with the unimpaired arm supported by a passive exoskeleton. Performance of the trunk and upper limbs was evaluated before treatment, after treatment and at six months follow up with clinical scales and an instrumented evaluation. A reaching test executed with the exoskeleton was used to assess changes in performance of both arms. The treatment based on the unimpaired arm's movements executed with a correct body posture led to benefits in control of the trunk and of both the trained and the untrained arm. The amount of impaired arm improvement in the Fugl-Meyer score was comparable to the outcome of robotic treatments focused directly on this arm. Our results highlight the importance of taking into account all body schema in the rehabilitation robotic program, instead of focusing only on the impaired side of the body.


Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy.
The structure of the cornea is vital to its transparency, and dystrophies that disrupt corneal organization are highly heritable. To understand the genetic aetiology of Fuchs endothelial corneal dystrophy (FECD), the most prevalent corneal disorder requiring transplantation, we conducted a genome-wide association study (GWAS) on 1,404 FECD cases and 2,564 controls of European ancestry, followed by replication and meta-analysis, for a total of 2,075 cases and 3,342 controls. We identify three novel loci meeting genome-wide significance (P<5 × 10-8): KANK4 rs79742895, LAMC1 rs3768617 and LINC00970/ATP1B1 rs1200114. We also observe an overwhelming effect of the established TCF4 locus. Interestingly, we detect differential sex-specific association at LAMC1, with greater risk in women, and TCF4, with greater risk in men. Combining GWAS results with biological evidence we expand the knowledge of common FECD loci from one to four, and provide a deeper understanding of the underlying pathogenic basis of FECD.