Pay communication, justice, and affect: The asymmetric effects of process and outcome pay transparency on counterproductive workplace behavior.
Grounded on uncertainty management theory, the current research examines the role of employee justice perceptions in explaining the distinct effects of two forms of pay transparency-process versus outcome pay transparency-on counterproductive workplace behavior (CWB). Study 1, a field study of 321 employees, revealed that process pay transparency is inversely related to CWB targeting the organization (i.e., less CWB-O), with this effect explained by enhanced employee procedural justice perceptions. It also indicated, however, that among employees perceiving their pay position as being lower than that of referent others, outcome pay transparency is positively associated with both CWB-O and CWB-I (i.e., CWB targeting other employees), with this effect explained by reduced employee distributive justice perceptions. Study 2, using an online simulation-based experiment conducted on 394 employees and assessing actual deception behaviors (targeting both the agency sponsoring the study and other participants in the study), replicated these findings and extended our understanding of the negative consequences of outcome pay transparency on CWB. Specifically, when pay allocations were transparent (vs. secretive) and participant's pay was manipulated to be lower (vs. higher) than that of teammates, participants reported lower distributive justice perceptions leading to heightened deception behaviors, with this effect explained by a more negative emotional state. Theoretical and practical implications of both the positive and negative consequences of pay transparency on CWB are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Pad per day usage, urinary incontinence and urinary tract infections in nursing home residents.
many elderly suffer from urinary incontinence and use absorbent pads. Pad use per day (PPD) is a frequently used measure of urinary incontinence. Nursing home residents are often dependent on help from nursing staff to change pads. This study was performed in order to determine whether PPD is a reliable method to quantify urinary incontinence in nursing home residents. Furthermore, the association between urinary tract infections (UTIs), PPD and fluid intake was studied. data were retrieved from a multicentre, prospective surveillance among nursing home residents. Data on the use of absorbent pads, fluid intake and incontinence volumes were collected during 48 h. During a 1-year follow-up period, data on UTIs were collected. in this study, 153 residents were included, of whom 118 (77%) used absorbent pads. Residents who used absorbent pads were at increased risk of developing UTIs compared to residents who did not use pads (41 vs 11%; P = 0.001). Daily fluid intake was not associated with UTIs (P = 0.46). The number of pad changes showed no correlation with the risk of developing UTIs (P = 0.62). Patients with a given PPD presented a wide range of incontinence volumes. the use of absorbent pads is associated with an increased risk of developing UTIs. PPD and daily fluid intake are not correlated with the risk of developing UTIs. PPD is an unreliable measure of urinary incontinence in nursing home residents.


Frequently rearranged and overexpressed δ-catenin is responsible for low sensitivity of prostate cancer cells to androgen receptor and β-catenin antagonists.
The mechanism of prostate cancer (PCa) progression towards the hormone refractory state remains poorly understood. Treatment options for such patients are limited and present a major clinical challenge. Previously, δ-catenin was reported to promote PCa cell growth in vitro and its increased level is associated with PCa progression in vivo. In this study we show that re-arrangements at Catenin Delta 2 (CTNND2) locus, including gene duplications, are very common in clinically significant PCa and may underlie δ-catenin overexpression. We find that δ-catenin in PCa cells exists in a complex with E-cadherin, p120, and α- and β-catenin. Increased expression of δ-catenin leads to its further stabilization as well as upregulation and stabilization of its binding partners. Resistant to degradation and overexpressed δ-catenin isoform activates Wnt signaling pathway by increasing the level of nuclear β-catenin and subsequent stimulation of Tcf/Lef transcription targets. Evaluation of responses to treatments, with androgen receptor (AR) antagonist and β-catenin inhibitors revealed that cells with high levels of δ-catenin are more resistant to killing with single agent treatment than matched control cells. We show that combination treatment targeting both AR and β-catenin networks is more effective in suppressing tumor growth than targeting a single network. In conclusion, targeting clinically significant PCa with high levels of δ-catenin with anti-androgen and anti β-catenin combination therapy may prevent progression of the disease to a castration-resistant state and, thus, represents a promising therapeutic strategy.


Economic evaluation of linezolid, flucloxacillin and vancomycin in the empirical treatment of cellulitis in UK hospitals: a decision analytical model.
Standard antibiotic treatment of infections has become more difficult and costly due to treatment failure associated with the rise in bacterial resistance. New antibiotics that can overcome such resistant pathogens have the potential for great clinical and economic impact. Linezolid is a new antibiotic that is effective in the treatment of both antibiotic-susceptible and antibiotic-resistant Gram-positive bacterial infections, including those resistant to other available antibiotics. This breadth of activity is unique in existing antibiotics for Gram-positive bacteria and serves as the rationale for exploring the hypothesis that linezolid is an appropriate choice when considering empirical treatment of cellulitis in complicated or compromised patients in the nosocomial setting. A decision-modelling approach was used to compare the predicted first-line treatment efficacy and direct medical costs of linezolid with standard treatment of cellulitis among hospitalized patients. For the purposes of this analysis, standard care is defined along two main pathways: (1) initiating care with intravenous (iv) flucloxacillin, switching to vancomycin if the pathogen is found to be resistant to flucloxacillin, or maintaining flucloxacillin if the pathogen is found susceptible, or when culture and sensitivity analysis is inconclusive; or (2) initiating care with vancomycin, switching to iv flucloxacillin if the pathogen is found susceptible to flucloxacillin, maintaining vancomycin if the infection is found resistant, or when culture and sensitivity are inconclusive. For those patients taking iv flucloxacillin, a switch to oral flucloxacillin was allowed when clinically appropriate. We hypothesized that the cost of care of initiating treatment with linezolid would be less than that for both vancomycin and flucloxacillin in resistance risk ranges typically encountered in UK hospitals. In addition, while the registration trials showed equivalence of linezolid with the comparators in known or suspected methicillin-resistant Staphylococcus aureus (MRSA) and in known or suspected methicillin-susceptible Staphylococcus aureus (MSSA) (vancomycin and oxacillin) respectively, we hypothesized that first-line success rates would be higher in empiric treatment with linezolid. Efficacy data were obtained from recent clinical trials with linezolid and standard treatment, and medical resource utilization was obtained from an expert panel of clinicians who were questioned regarding resistant and susceptible infections separately. UK hospital direct medical costs of treatment were determined using standard costing techniques. Base case analyses assumed a residual 80% unknown pathogen rate after culture and susceptibility based on a physician survey and supported in the literature. The analysis in this model predicts that initiating empirical treatment of cellulitis with linezolid will (1) result in higher overall success rates than flucloxacillin for first-line treatment, regardless of resistance risk and (2) be less costly than initiating treatment with flucloxacillin when the likelihood of a patient being infected by a resistant pathogen is greater than 24.1%. Furthermore, initiating treatment with linezolid is predicted to result in higher overall success rates and be less costly than vancomycin across the entire spectrum of the patients' risk of being infected by a resistant pathogen.


[A new (brachymelic) type of primordial dwarfism (author's transl)].
Second report of an apparently new type of primordial dwarfism characterized by severe intrauterine and postnatal growth retardation, striking craniofacial deformities and a peculiar osteochondrodysplasia. The major clinical findings are microcephaly, hypotrichosis, bulging eyes, prominent nose, micrognathia and short extremities. The osteochondrodysplasia is characterized by short and bowed humeri and femora with absent ossification of the femoral necks, small and dysplastic iliac wings, strikingly retarded ossification of the epiphyses and shortened metacarpal I and middle phalanges II-V. Possible this condition is caused by the homozygous state of mutant gene. The brachymelic type of primordial dwarfism differs from other forms of primordial dwarfism (particularly from case I of Seckel) by its skeletal abnormalities. The cases described by Seckel (and sometimes referred to as Seckel or bird-headed dwarfism) are heterogenous: Seckel dwarfism apparently does not exist as a nosologic entity.


Non-alcoholic Fatty Liver Disease Is a Risk Factor for Type 2 Diabetes in Middle-aged Japanese Men and Women.
Objective Emerging studies have focused on the association between non-alcoholic fatty liver disease (NAFLD) and the risk of type 2 diabetes mellitus (T2DM). We aimed to investigate whether NAFLD diagnosed by ultrasonography could predict the risk of future T2DM in a Japanese middle-aged health check population. Methods We conducted a 10-year observational study in a health checkup population of middle-aged Japanese men and women at Hidaka Hospital from 2004 to 2013. We excluded cases with an alcohol intake exceeding 20 g/day and those with impaired glucose tolerance. The remaining 1,544 men and 864 women were classified into fatty liver and non-fatty liver groups based on the findings of abdominal ultrasonography. Both groups were followed for the development of diabetes. A multiple regression analysis was performed for each variable to predict the risk of future diabetes. Results The median age of the participants was 46.0 years at the entry, and the follow-up period was 10 years. The incidence of diabetes in the fatty liver group was 12.5% (29/232) in men and 26.3% (10/38) in women, whereas the incidence of diabetes in the non-fatty liver group was 2.5% (34/1,312) in men and 1.8% (15/826) in women. The relative risk of diabetes associated with fatty liver was 4.8 [95% confidence interval (CI) 3.0-7.8, p<0.0001] in men and 14.5 (95% CI 7.0-30.1, p<0.0001) in women. Conclusion NAFLD was a significant predictor for future diabetes in a Japanese middle-aged health check population, especially in women.


Exposure in vivo versus operant graded activity in chronic low back pain patients: results of a randomized controlled trial.
Since pain-related fear may contribute to the development and maintenance of chronic low back pain (CLBP), an exposure in vivo treatment (EXP) was developed for CLBP patients. We examined the effectiveness as well as specific mediating mechanisms of EXP versus operant graded activity (GA) directly and 6 months post-treatment in a multi-centre randomized controlled trial. In total, 85 patients suffering from disabling non-specific CLBP reporting at least moderate pain-related fear were randomly allocated to EXP or GA. It was demonstrated that EXP, despite excelling in diminishing pain catastrophizing and perceived harmfulness of activities, was equally effective as GA in improving functional disability and main complaints, although the group difference almost reached statistical significance favouring EXP. Both treatment conditions did not differ in pain intensity and daily activity levels either. Nor was EXP superior to GA in the subgroup of highly fearful patients. Irrespective of treatment, approximately half the patients reported clinically relevant improvements in main complaints and functional disability, although for the latter outcome the group difference was almost significant favouring EXP. Furthermore, the effect of EXP relative to GA on functional disability and main complaints was mediated by decreases in catastrophizing and perceived harmfulness of activities. In sum, this study demonstrates that up to 6 months after treatment EXP is an effective treatment, but not more effective than GA, in moderately to highly fearful CLBP patients, although its superiority in altering pain catastrophizing and perceived harmfulness of activities is clearly established. Possible explanations for these findings are discussed.


Evidence for a novel blood RNA diagnostic for pediatric appendicitis: the riboleukogram.
To test the hypothesis that gene expression analysis of circulating white blood cells and/or plasma cytokines could be used to improve diagnostic accuracy in children being evaluated for appendicitis. We recruited 28 children being evaluated for abdominal pain from a tertiary pediatric emergency department. Twenty patients were used as a training cohort and 8 patients as a validation cohort. After consent was obtained, blood was processed for plasma cytokine analysis and RNA gene expression. Alvarado and pediatric appendicitis scores were obtained. Principal components analysis was used to explore global differences in gene expression. The random forest method was used to classify patients into those with and without appendicitis in the prospective cohort. Comparisons were made evaluating clinical scoring systems, cytokine analysis, and gene expression analysis to accurately predict appendicitis. The random forest method accurately predicted appendicitis in 4 of 5 patients in the prospective cohort. Cytokine analysis was not as accurate as gene expression analysis; however, it did accurately rule out all 3 patients in the prospective cohort. Pediatric appendicitis scores and Alvarado scores were not useful for predicting appendicitis. Our findings provide proof of technical feasibility and support the diagnostic potential of plasma cytokines to rule out and riboleukograms to rule in the diagnosis of appendicitis.


Dependency of active pressure and equation of state on stiffness of wall.
Autonomous motion and motility are hallmarks of active matter. Active agents, such as biological cells and synthetic colloidal particles, consume internal energy or extract energy from the environment to generate self-propulsion and locomotion. These systems are persistently out of equilibrium due to continuous energy consumption. It is known that pressure is not always a state function for generic active matter. Torque interaction between active constituents and confinement renders the pressure of the system a boundary-dependent property. The mechanical pressure of anisotropic active particles depends on their microscopic interactions with a solid wall. Using self-propelled dumbbells confined by solid walls as a model system, we perform numerical simulations to explore how variations in the wall stiffness influence the mechanical pressure of dry active matter. In contrast to previous findings, we find that mechanical pressure can be independent of the interaction of anisotropic active particles with walls, even in the presence of intrinsic torque interaction. Particularly, the dependency of pressure on the wall stiffness vanishes when the stiffness is above a critical level. In such a limit, the dynamics of dumbbells near the walls are randomized due to the large torque experienced by the dumbbells, leading to the recovery of pressure as a state variable of density.


Future Priorities in Tackling Infections Due to Brain-Eating Amoebae.
Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent key priorities for improving outcomes from infections due to brain-eating amoebae.


DNA barcoding in surveys of small mammal communities: a field study in Suriname.
The performance of DNA barcoding as a tool for fast taxonomic verification in ecological assessment projects of small mammals was evaluated during a collecting trip to a lowland tropical rainforest site in Suriname. We also compared the performance of tissue sampling onto FTA CloneSaver cards vs. liquid nitrogen preservation. DNA barcodes from CloneSaver cards were recovered from 85% of specimens, but DNA degradation was apparent, because only 36% of sequence reads were long (over 600 bp). In contrast, cryopreserved tissue delivered 99% barcode recovery (97% > 600 bp). High humidity, oversampling or tissue type may explain the poor performance of CloneSaver cards. Comparison of taxonomic assignments made in the field and from barcode results revealed inconsistencies in just 3.4% of cases and most of the discrepancies were due to field misidentifications (3%) rather than sampling/analytical error (0.5%). This result reinforces the utility of DNA barcoding as a tool for verification of taxonomic identifications in ecological surveys, which is especially important when the collection of voucher specimens is not possible.


Transrectal ultrasonographic findings in patients with hemospermia.
Hemospermia causes anxiety in many men. Its etiology includes inflammatory disorders, vascular lesions, malignancies and congenital anomalies. With the advent of modern transrectal ultrasonography (TRUS) and magnetic resonance imaging technology, we can now visualize the internal structures of the seminal vesicles and prostate, and identify a more accurate etiology for hemospermia. This study was performed to assess the efficacy of TRUS in the evaluation of hemospermia. TRUS was used to evaluate 40 patients with hemospermia. Patients' ages ranged from 20 to 72 years, with an average age of 41 years. The duration of symptoms was 3 days to 10 years, (average age 12.4 months). Apart from three patients with hepatitis, there was no major illness found in the medical histories. TRUS was performed with a B & K, type 3535 transrectal transducer device, with an 1850 multiplane probe. TRUS revealed abnormalities in 33 (83%) of 40 patients, which included ejaculatory duct cysts, müllerian duct cysts, asymmetric seminal vesicle dilatation, preprostatic vein engorgement and prostatic enlargement. There were stones in the ejaculatory ducts, ejaculatory duct cysts, müllerian duct cysts or prostate. Nine patients with prostatic stones were under 40 years-of-age. Other than the development of stones, there were no significant differences between patients less than 40 years-of-age and those more than 40 years old. The results suggest that TRUS is an effective method for examining the seminal vesicles, ejaculatory duct and prostate complex. Sonoguided aspiration, injection of contrast medium or biopsy can further help to differentiate the nature of hemospermia.


[Prevalence of systemic inflammatory syndromes at a tertiary pediatric intensive care unit].
To assess the prevalence of systemic inflammatory syndromes on admission to a tertiary-care university pediatric intensive care unit (ICU), and relate this to length of hospital stay, risk of death and mortality rate. Cross-sectional, prospective, observational study, including all patients admitted to the Hospital de Clinicas de Porto Alegre (HCPA) ICU between August 1st 1999 and July 31st 2000. Patient demographic variables were considered together with the risk of mortality on admission, co-morbidities, length of hospital stay and ICU outcome, in addition to variables that characterize the systemic inflammatory syndromes (systemic inflammatory response syndrome, sepsis, severe sepsis and septic shock). We studied 447 admissions of 388 patients; 54% were male, with a median age of 20 months. The prevalence of systemic inflammatory response syndrome (SIRS) was 68%: 2/3 infectious (sepsis, severe sepsis or septic shock) and 1/3 non-infectious. Risk of mortality scores for patients with infectious SIRS were higher than for those with non-infectious SIRS (6.75% [P25 = 2.25 - P75 = 21.3] vs. 2.35% [P25 = 1.1 - P75 = 6.7]; p = 0) and increased according to SIRS severity (2.9; 10.85, 43.9%; p < 0.05). The observed mortality was 12% for patients with SIRS and 5.8% for those without SIRS (p = 0.057); the observed mortality for infectious SIRS was 14.9% and for non-infectious 6.3% (p = 0.041). The period spent in ICU for infectious SIRS was longer than for non-infectious cases: 3 days (P25 = 2 - P75 = 7) vs. 2 days (P25 = 1.5 - P75 = 4); p = 0.006. The prevalence rate of patients with systemic inflammatory response syndrome upon admission to HCPA pediatric intensive care unit was elevated, with a predominance of infectious syndromes, responsible for longer stays, increased risk of mortality and increased mortality of patients during the period evaluated.


Open-Endedness for the Sake of Open-Endedness.
Natural evolution keeps inventing new complex and intricate forms and behaviors. Digital evolution and genetic algorithms fail to create the same kind of complexity, not just because we still lack the computational resources to rival nature, but because (it has been argued) we have not understood in principle how to create open-ended evolving systems. Much effort has been made to define such open-endedness so as to create forms of increasing complexity indefinitely. Here, however, a simple evolving computational system that satisfies all such requirements is presented. Doing so reveals a shortcoming in the definitions for open-ended evolution. The goal to create models that rival biological complexity remains. This work suggests that our current definitions allow for even simple models to pass as open-ended, and that our definitions of complexity and diversity are more important for the quest of open-ended evolution than the fact that something runs indefinitely.


Purification of membrane proteins free from conventional detergents: SMA, new polymers, new opportunities and new insights.
Membrane proteins remain a somewhat enigmatic group of biomolecules. On the one hand they mediate some of the most important processes in biology with molecular mechanisms that are often elegantly complex. On the other hand they are exceptionally challenging to produce, making studies of membrane protein structure and function among the most difficult projects undertaken by biochemists. The central issue with studies of a membrane protein has been the need to extract them from their native lipid environment before purification and production of a homogenous sample. Historical approaches have utilized detergent solubilisation but these often lead to a sample with low activity and stability. In the past 15 years a new approach that focuses on preserving the local lipid environment surrounding the membrane proteins has been developed. The latest, and perhaps most complete, incarnation of this method has been the use of polymers based on styrene maleic acid (SMA) to stabilise nanoscale discs of lipid that contain membrane proteins. In this review we examine the range of SMA-related polymers that have now been shown to have utility in the production of membrane proteins. We discuss the differences between the polymers and attempt to discover rules and trends that explain their behavior.


Effect of a high-kappa environment on charge carrier mobility in graphene.
It is widely assumed that the dominant source of scattering in graphene is charged impurities in a substrate. We have tested this conjecture by studying graphene placed on various substrates and in high-kappa media. Unexpectedly, we have found no significant changes in carrier mobility either for different substrates or by using glycerol, ethanol, and water as a top dielectric layer. This suggests that Coulomb impurities are not the scattering mechanism that limits the mean free path attainable for graphene on a substrate.


NMR imaging of fluid exchange between macropores and matrix in eogenetic karst.
Sequential time-step images acquired using nuclear magnetic resonance (NMR) show the displacement of deuterated water (D(2)O) by fresh water within two limestone samples characterized by a porous and permeable limestone matrix of peloids and ooids. These samples were selected because they have a macropore system representative of some parts of the eogenetic karst limestone of the Biscayne Aquifer in southeastern Florida. The macroporosity, created by the trace fossil Ophiomorpha, is principally well connected and of centimeter scale. These macropores occur in broadly continuous stratiform zones that create preferential flow layers within the hydrogeologic units of the Biscayne. This arrangement of porosity is important because in coastal areas, it could produce a preferential pathway for salt water intrusion. Two experiments were conducted in which samples saturated with D(2)O were placed in acrylic chambers filled with fresh water and examined with NMR. Results reveal a substantial flux of fresh water into the matrix porosity with a simultaneous loss of D(2)O. Specifically, we measured rates upward of 0.001 mL/h/g of sample in static conditions, and perhaps as great as 0.07 mL/h/g of sample when fresh water continuously flows past a sample at velocities less than those found within stressed areas of the Biscayne. These experiments illustrate how fresh water and D(2)O, with different chemical properties, migrate within one type of matrix porosity found in the Biscayne. Furthermore, these experiments are a comparative exercise in the displacement of sea water by fresh water in the matrix of a coastal, karst aquifer since D(2)O has a greater density than fresh water.


Enhancing questioning skills through child avatar chatbot training with feedback.
Training child investigative interviewing skills is a specialized task. Those being trained need opportunities to practice their skills in realistic settings and receive immediate feedback. A key step in ensuring the availability of such opportunities is to develop a dynamic, conversational avatar, using artificial intelligence (AI) technology that can provide implicit and explicit feedback to trainees. In the iterative process, use of a chatbot avatar to test the language and conversation model is crucial. The model is fine-tuned with interview data and realistic scenarios. This study used a pre-post training design to assess the learning effects on questioning skills across four child interview sessions that involved training with a child avatar chatbot fine-tuned with interview data and realistic scenarios. Thirty university students from the areas of child welfare, social work, and psychology were divided into two groups; one group received direct feedback (n = 12), whereas the other received no feedback (n = 18). An automatic coding function in the language model identified the question types. Information on question types was provided as feedback in the direct feedback group only. The scenario included a 6-year-old girl being interviewed about alleged physical abuse. After the first interview session (baseline), all participants watched a video lecture on memory, witness psychology, and questioning before they conducted two additional interview sessions and completed a post-experience survey. One week later, they conducted a fourth interview and completed another post-experience survey. All chatbot transcripts were coded for interview quality. The language model's automatic feedback function was found to be highly reliable in classifying question types, reflecting the substantial agreement among the raters [Cohen's kappa (κ) = 0.80] in coding open-ended, cued recall, and closed questions. Participants who received direct feedback showed a significantly higher improvement in open-ended questioning than those in the non-feedback group, with a significant increase in the number of open-ended questions used between the baseline and each of the other three chat sessions. This study demonstrates that child avatar chatbot training improves interview quality with regard to recommended questioning, especially when combined with direct feedback on questioning.


A reversible water-based electrostatic adhesive.
Commercial adhesives typically fall into two categories: structural or pressure sensitive. Structural glues rely on covalent bonds formed during curing and provide high tensile strength whilst pressure-sensitive adhesives use physical bonding to provide weaker adhesion, but with considerable convenience for the user. Here, a new class of adhesive is presented that is also reversible, with a bond strength intermediate between those of pressure-sensitive and structural adhesives. Complementary water-based formulations incorporating oppositely charged polyelectrolytes form electrostatic bonds that may be reversed through immersion in a low or high pH aqueous environment. This electrostatic adhesive has the advantageous property that it exhibits good adhesion to low-energy surfaces such as polypropylene. Furthermore, it is produced by the emulsion copolymerization of commodity materials, styrene and butyl acrylate, which makes it inexpensive and opens the possibility of industrial production. Bio-based materials have been also integrated into the formulations to further increase sustainability. Moreover, unlike other water-based glues, adhesion does not significantly degrade in humid environments. Because such electrostatic adhesives do not require mechanical detachment, they are appropriate for the large-scale recycling of, e.g., bottle labels or food packaging. The adhesive is also suitable for dismantling components in areas as varied as automotive parts and electronics.


Cervical Fracture Stabilization within 72 Hours of Injury is Associated with Decreased Hospitalization Costs with Comparable Perioperative Outcomes in a Propensity Score-Matched Cohort.
Prior studies have indicated that early decompression of traumatic cervical fractures can be performed safely and is associated with improved outcomes, though the economic impact of the timing of surgery in the American population has not been studied. After adjusting for patient, hospital, and injury confounders, we performed propensity score modeling (PSM) on a large clinical administrative database to determine associated costs depending upon timing of surgery for acute cervical fracture. A total of 3,348 patients with surgically treated, traumatic, cervical fractures were identified. Patients were sorted into early (within 72 hours of admission) and late (beyond 72 hours) surgery groups. PSM was able to match 2,132 early and late surgery patients on age, comorbidity, expected payer, trauma severity, hospital type, urgent admission, and surgical approach. Perioperative complications, mortality, and resource utilization were assessed. Late surgery was more frequently associated with increased age, more comorbidities, higher ICISS score, and non-private insurance. Following PSM matching, there were no significant, preoperative differences between early and late surgery groups. Surgery performed after 72 hours was associated with an increase in in-hospital complications (OR=1.3). The early surgery group was associated with decreased length of stay (11 days vs. 16 days, p <0.0001) and hospital charges ($237,786 v. $282,727, p <0.0001). After controlling for potential confounding differences through PSM matching and multivariate analyses, we found late surgery independently associated with increased in-hospital complications, length of stay, and hospital resource utilization. These data suggest surgery within 72 hours may decrease resource utilization without a corresponding increase in postoperative morbidity.


Canadians without regular medical doctors. Who are they?
Because having a regular medical doctor is associated with positive outcomes, this study attempted to determine the characteristics of Canadians without regular doctors so that alternative methods of delivering care to people with those characteristics can be studied. Secondary data analysis of the National Population Health Survey using bivariate analyses and logistic regression. A total of 15,777 respondents older than 20 years. Responses to the question "Do you have a regular medical doctor?" and analysis of 11 variables covering demographics, health status, and lifestyle factors. One in seven respondents did not have a regular doctor. Younger respondents, men, single people, poorer respondents, respondents who perceived themselves in better health, recent immigrants, those without confidants, and smokers were more likely not to have regular doctors. Comparing provinces, participants from Quebec were least likely to have regular doctors. Primary care reform might need to consider alternative ways of providing care to certain people. Future primary care programs could be targeted to improve coverage of relatively underserviced people, particularly men, people on low incomes, those without confidants, and recent immigrants.


Impact of gamma radiation dose on sterility and quality parameters of Anastrepha fraterculus (Diptera: Tephritidae).
Anastrepha fraterculus (Wiedemann, 1830) (Diptera: Tephritidae) is a major fruit pest, which is basicaly controlled using insecticides, which represents a risk to beneficial arthropods, human health and food contamination. The sterile insect technique (SIT) is a potential alternative tool for the management of this pest, however, only conflicting data is found regarding the optimal dose to achieve sterility. Thus, this study evaluated the effect of gamma radiation doses (0, 40, 50, 60 and 70 Gy) on male and female reproductive sterility, gonads morphometry, emergence, flight ability, and longevity under nutritional stress of A. fraterculus. Full female sterility was achieved at 50 Gy, while full male sterility was achieved at 70 Gy. Both ovarian and testicular sizes were affected by irradiation, while no influence was observed on the quality parameters evaluated. Our results suggest that 70 Gy applied 48 h before adult emergence can be used to sterilize A. fraterculus in a SIT programme.


School consultation: a review of research on issues unique to the school environment.
To provide clinicians with current information to assist in their consultations to schools on 4 major topics that are unique to the school environment and of serious concern to educators: absenteeism, disciplinary referrals, retention (non-promotion), and dropping out. Computer literature searches and the major journals of the various school disciplines were used to identify empirically based articles with sound methodology. Information on each of the 4 issues is presented as general characteristics, characteristics of psychopathology, prevention and treatment, and implications for consultation. Findings are largely general, with little specific information on level of intelligence, learning disorders, psychopathology, or family stressors. Students under each topic have varied presentations. However, many pupils with absenteeism, disciplinary referrals, or retention appear to be characterized by chronic and serious academic and/or behavior problems, all of which can predate dropping out. Considerable research is still needed on all 4 school issues, especially psychopathology. Nevertheless, consultants can reasonably first help schools to identify students at risk for the 4 outcomes, followed by appropriate screening/evaluation to indicate more clearly their true intervention needs. The ongoing process can further educate school staff about psychiatric disorders in their most problematic students.


[Giant cavernous hemangioma of the orbit (case report)].
The following case demonstrates a successful en bloc removal of a massive cavernous hemangioma of the orbit via vertical transpalpebral approach with postoperative improvement of optic nerve condition and optimal cosmetic result.


Attributes and perspectives of public providers related to provision of medical abortion at public health facilities in Vietnam: a cross-sectional study in three provinces.
The purpose of this study was to investigate attributes of public service providers associated with the provision of medical abortion in Vietnam. We conducted a cross-sectional study via interviewer-administered questionnaire among abortion providers from public health facilities in Hanoi, Khanh Hoa, and Ho Chi Minh City in Vietnam between August 2011 and January 2012. We recruited abortion providers at all levels of Vietnam's public health service delivery system. Participants were questioned about their medical abortion provision practices and perspectives regarding abortion methods. A total of 905 providers from 62 health facilities were included, comprising 525 (58.0%) from Hanoi, 122 (13.5%) from Khanh Hoa, and 258 (28.5%) from Ho Chi Minh City. The majority of providers were female (96.7%), aged ≥25 years (94%), married (84.4%), and had at least one child (89%); 68.9% of providers offered only manual vacuum aspiration and 31.1% performed both medical abortion and manual vacuum aspiration. Those performing both methods included physicians (74.5%), midwives (21.7%), and nurses (3.9%). Unadjusted analyses showed that female providers (odds ratio 0.1; 95% confidence interval 0.01-0.30) and providers in rural settings (odds ratio 0.3; 95% confidence interval 0.08-0.79) were less likely to provide medical abortion than their counterparts. Obstetricians and gynecologists were more likely to provide medical abortion than providers with nursing/midwifery training (odds ratio 22.2; 95% confidence interval 3.81-129.41). The most frequently cited advantages of medical abortion for providers were that no surgical skills are required (61.7%) and client satisfaction is better (61.0%). Provision of medical abortion in Vietnam is lower than provision of manual vacuum aspiration. While the majority of abortion providers are female midwives in Vietnam, medical abortion provision is concentrated in urban settings among physicians. Individuals providing medical abortion found that the method yields high client satisfaction.


Change in Pain Status and Subsequent Opioid and Marijuana Use Among Long-Term Adult Survivors of Childhood Cancer.
We evaluated pain status change and associations with subsequent opioid/marijuana use among 1208 adult survivors of childhood cancer. Pain status and opioid/marijuana were self-reported at baseline and follow-up evaluation (mean interval = 4.2 years). Over time, 18.7% of survivors endorsed persistent/increasing significant pain; 4.8% and 9.0% reported having used opioids and marijuana at follow-up. Persistent/increased (vs none/decreased) pain, persistent/increased (vs none/decreased) anxiety, and lack of health insurance increased odds of subsequent opioid use by 7.69-fold (95% confidence interval [CI] = 3.71 to 15.95), 2.55-fold (95% CI = 1.04 to 6.24), and 2.50-fold (95% CI = 1.07 to 5.82), respectively. Persistent/increased (vs none/decreased) depression increased odds of subsequent marijuana use by 2.64-fold (95% CI = 1.10 to 6.33).


Measurement accuracy of prototype non-contrast, compressed sensing-based, respiratory motion-resolved whole heart cardiovascular magnetic resonance angiography for the assessment of thoracic aortic dilatation: comparison with computed tomography angiography.
Patients with thoracic aortic dilatation who undergo annual computed tomography angiography (CTA) are subject to repeated radiation and contrast exposure. The purpose of this study was to evaluate the feasibility of a non-contrast, respiratory motion-resolved whole-heart cardiovascular magnetic resonance angiography (CMRA) technique against reference standard CTA, for the quantitative assessment of cardiovascular anatomy and monitoring of disease progression in patients with thoracic aortic dilatation. METHODS: Twenty-four patients (68.6 ± 9.8 years) with thoracic aortic dilatation prospectively underwent clinical CTA and research 1.5T CMRA between July 2017 and November 2018. Scans were repeated in 15 patients 1 year later. A prototype free-breathing 3D radial balanced steady-state free-precession whole-heart CMRA sequence was used in combination with compressed sensing-based reconstruction. Area, circumference, and diameter measurements were obtained at seven aortic levels by two experienced and two inexperienced readers. In addition, area and diameter measurements of the cardiac chambers, pulmonary arteries and pulmonary veins were also obtained. Agreement between the two modalities was assessed with intraclass correlation coefficient (ICC) analysis, Bland-Altman plots and scatter plots. Area, circumference and diameter measurements on a per-level analysis showed good or excellent agreement between CTA and CMRA (ICCs > 0.84). Means of differences on Bland-Altman plots were: area 0.0 cm2 [- 1.7; 1.6]; circumference 1.0 mm [- 10.0; 12.0], and diameter 0.6 mm [- 2.6; 3.6]. Area and diameter measurements of the left cardiac chambers showed good agreement (ICCs > 0.80), while moderate to good agreement was observed for the right chambers (all ICCs > 0.56). Similar good to excellent inter-modality agreement was shown for the pulmonary arteries and veins (ICC range 0.79-0.93), with the exception of the left lower pulmonary vein (ICC < 0.51). Inter-reader assessment demonstrated mostly good or excellent agreement for both CTA and CMRA measurements on a per-level analysis (ICCs > 0.64). Difference in maximum aortic diameter measurements at baseline vs follow up showed excellent agreement between CMRA and CTA (ICC = 0.91). The radial whole-heart CMRA technique combined with respiratory motion-resolved reconstruction provides comparable anatomical measurements of the thoracic aorta and cardiac structures as the reference standard CTA. It could potentially be used to diagnose and monitor patients with thoracic aortic dilatation without exposing them to radiation or contrast media.


Hepatocyte nuclear factor 1B deletion, but not intragenic mutation, might be more susceptible to hypomagnesemia.
HNF1B syndrome is caused by defects in the hepatocyte nuclear factor 1B (HNF1B) gene, which leads to maturity-onset diabetes of the young type 5 and congenital organ malformations. This study aimed to identify a gene defect in a patient presenting with diabetes and severe diarrhea, while also analyzing the prevalence of hypomagnesemia and its correlation with the HNF1B genotype. Whole exome sequencing was used to identify responsible point mutations and small indels in the proband and their family members. Multiplex ligation-dependent probe amplification was carried out to identify HNF1B deletions. Furthermore, an analysis of published data on 539 cumulative HNF1B cases, from 29 literature sources, was carried out to determine the correlation between the HNF1B genotype and the phenotype of serum magnesium status. Using multiplex ligation-dependent probe amplification, we identified a de novo heterozygous HNF1B deletion in the patient, who showed dorsal pancreas agenesis and multiple kidney cysts, as detected by magnetic resonance imaging. Magnesium supplementation effectively alleviated the symptoms of diarrhea. Hypomagnesemia was highly prevalent in 192 out of 354 (54.2%) patients with HNF1B syndrome. Compared with patients with intragenic mutations, those with HNF1B deletions were more likely to suffer from hypomagnesemia, with an odds ratio of 3.1 (95% confidence interval 1.8-5.4). Hypomagnesemia is highly prevalent in individuals with HNF1B syndrome, and those with HNF1B deletion are more susceptible to developing hypomagnesemia compared with those with intragenic mutations. The genotype-phenotype associations in HNF1B syndrome have significant implications for endocrinologists in terms of genotype detection, treatment decisions and prognosis assessment.


The distribution of relaxin receptors in the anterior segment of primary open-angle glaucoma patients.
Relaxin is a polypeptide hormone produced by the corpus luteum and the decidua in females and by the prostate in males. It has vasodilatory and antifibrotic effects. In the past, it has been reported that injection of relaxin hormone has caused a reduction in the intraocular pressure although its mechanism has not yet been fully understood and the expression of relaxin receptors has not yet been evident in the human eye. Therefore, the purpose of this current study was to examine the presence of relaxin receptors in the human eye anterior segment. This is an interventional non-randomized study. Patients with primary open-angle glaucoma who underwent trabeculectomy were recruited. During the surgery, a punch biopsy (including the cornea, sclera, trabecular meshwork, and Schlemm's canal) was taken and stained with hematoxylin-eosin, and immunohistochemistry staining for relaxin/insulin-like family peptide receptor 1 (RXFP1). A positive staining was noted for RXFP1 in the inner uveal, corneoscleral, and cribriform meshwork and Schlemm's canal's endothelium. Negative staining for RXFP1 was noted in the cornea and sclera. RXFP1 is present in the anterior segment drainage system of the human eye. Therefore, this receptor may have an active role in regulating the outflow facility and in the reduction of intraocular pressure.


Insulin resistance (HOMA-IR) and body fat (%) are associated to low intake of fruit and vegetables in Swedish, young adults: the cross-sectional lifestyle, biomarkers and atherosclerosis study.
In the cross-sectional Lifestyle, Biomarkers, and Atherosclerosis study (LBA study) we have previously reported a high prevalence (15%) of homeostasis model assessment of insulin resistance (HOMA-IR) in Swedish, young adults. The aim of the present study was to report the dietary habits of subjects 18.0-25.9 years, and to associate dietary habits to body composition measures; body mass index (BMI), body fat (%), waist circumference and to HOMA-IR, a risk marker for diabetes. The subjects (577 women and 257 men) filled in a validated computerized food frequency questionnaire. The questionnaire was based on recommendations from the Swedish national food administration. To associate the dietary habits to BMI, body fat (%), waist circumference and to HOMA-IR the subjects were divided in two groups. Subjects "eating as recommended" and subjects "eating less/more than recommended". Recommended intake of fish and seafood (P < 0.05), fruit and vegetables (P < 0.001), and sweets (P < 0.05) were associated to lower HOMA-IR values compared to subjects not eating as recommended. When split by sex no difference in HOMA-IR was detected with recommended intake of fish and seafood, but women eating fish and seafood as recommended had less body fat (%) (P < 0.05) compared to women not eating fish and seafood as recommended. Recommended intake of fruit and vegetables was associated to lower HOMA-IR in women (P < 0.01), and in women and men to less body fat (%) (P < 0.05) compared to subjects not eating the recommended 500 g of fruit and vegetables per day. Both women and men with higher consumption of sweets than recommended had higher HOMA-IR (P < 0.05), but no difference in the body composition measures BMI, body fat (%) or waist circumference compared to subjects eating sweets as recommended. The results highlight the importance of reducing a high intake of sweets and to increase the intake of fish, fruit and vegetables, in young adults, to reduce the risk of future diabetes.


Induction of hepatic metallothionein by feeding zinc to rats of depleted zinc status.
Induction of hepatic metallothionein was investigated in zinc-depleted rats after a single feeding (via stomach tube) of a complete diet with or without supplemental zinc. Subsequent to a maximum elevation in serum zinc (3.25 micrograms/ml) at 3 h, the rate of metallothionein synthesis increased 4.5-fold by 10 h after feeding. Changes in the rate of metallothionein synthesis coincided with similar changes in the level of translatable mRNA coding for metallothionein. Accumulation in liver of Zn2+ as metallothionein rose to a maximum by 12 h after diet administration and thereafter remained constant. Radioactive zinc (65Zn) included in the diet rapidly associated with newly formed metallothionein. Unlike Zn2+, 65Zn exhibited marked fluctuations within the 24-h period following feeding, indicating that zinc associated with metallothionein may be capable of exchange and/or dissociation. Changes in total liver 65Zn were accompanied by concomitant changes in metallothionein-bound 65Zn. This study has related (temporally) the metabolism of dietary zinc to the induction, apparently via transcription of mRNA, of hepatic metallothionein.


Higher titer hepatitis B core antibody predicts a higher risk of liver metastases and worse survival in patients with colorectal cancer.
There have been controversial voices on if hepatitis B virus infection decreases the risk of colorectal liver metastases or not. This study aims to the find the association between HBV infection and postoperative survival of colorectal cancer and the risk of liver metastases in colorectal cancer patients. Patients who underwent curative surgical resection for colorectal cancer between January 2011 and December 2012 were included. Patients were grouped according to anti-HBc. Differences in overall survival, time to progress, and hepatic metastasis-free survival between groups and significant predictors were analyzed. Three hundred twenty-seven colorectal cancer patients were comprised of 202 anti-HBc negative cases and 125 anti-HBc positive cases, and anti-HBc positive cases were further divided into high-titer anti-HBc group (39) and low-titer anti-HBc group (86). The high-titer anti-HBc group had significantly worse overall survival (5-Yr, 65.45% vs. 80.06%; P < .001), time to progress (5-Yr, 44.26% vs. 84.73%; P < .001), and hepatic metastasis-free survival (5-Yr, 82.44% vs. 94.58%; P = .029) than the low-titer group. Multivariate model showed anti-HBc ≥ 8.8 S/CO was correlated with poor overall survival (HR, 3.510; 95% CI, 1.718-7.17; P < .001), time to progress (HR, 5.747; 95% CI, 2.789-11.842; P < .001), and hepatic metastasis-free survival (HR, 3.754; 95% CI, 1.054-13.369; P = .041) in the anti-HBc positive cases. Higher titer anti-HBc predicts a potential higher risk of liver metastases and a worse survival in anti-HBc positive colorectal cancer patients.


The relationship between working memory, processing speed, verbal comprehension and FAS performance following traumatic brain injury.
To investigate the relationship of working memory, processing speed and verbal comprehension with FAS performance in individuals who had sustained a traumatic brain injury (TBI). Sixty-three patients with a TBI were grouped according to the presence of impaired verbal fluency performance and then compared on a number of cognitive and demographic variables. Following a TBI, working memory and processing speed had the greatest influence on verbal fluency performance. For those individuals who have not sustained a TBI, education, verbal intelligence, working memory and speed of information processing were related to FAS performance. The findings of the study indicate that FAS performance was related to verbal intelligence, working memory ability, attention and speed of information processing. The results further suggest that different variables are related to FAS performance following a TBI as compared with control group performances.


Data-Dependent Conditional Priors for Unsupervised Learning of Multimodal Data.
One of the major shortcomings of variational autoencoders is the inability to produce generations from the individual modalities of data originating from mixture distributions. This is primarily due to the use of a simple isotropic Gaussian as the prior for the latent code in the ancestral sampling procedure for data generations. In this paper, we propose a novel formulation of variational autoencoders, conditional prior VAE (CP-VAE), with a two-level generative process for the observed data where continuous z and a discrete c variables are introduced in addition to the observed variables x. By learning data-dependent conditional priors, the new variational objective naturally encourages a better match between the posterior and prior conditionals, and the learning of the latent categories encoding the major source of variation of the original data in an unsupervised manner. Through sampling continuous latent code from the data-dependent conditional priors, we are able to generate new samples from the individual mixture components corresponding, to the multimodal structure over the original data. Moreover, we unify and analyse our objective under different independence assumptions for the joint distribution of the continuous and discrete latent variables. We provide an empirical evaluation on one synthetic dataset and three image datasets, FashionMNIST, MNIST, and Omniglot, illustrating the generative performance of our new model comparing to multiple baselines.


A calix[4]arene-modified (Pc)Eu(Pc)Eu[T(C4A)PP]-based sensor for highly sensitive and specific host-guest electrochemical recognition.
A calix[4]arene (C4A)-functionalized (phthalocyaninato)(porphyrinato) europium(iii) triple-decker compound (Pc)Eu(Pc)Eu[T(C4A)PP] (1) is firstly designed, synthesized and prepared into well-organized films using a simple solution-processing quasi-Langmuir-Shäfer (QLS) method. The QLS film of 1 on an ITO (film 1/ITO) electrode, serving as a host-guest electrochemical recognition layer, is able to establish specific responses/interactions toward organic molecules with biological and drug interest including dopamine (DA), uric acid (UA), tyrosine (Tyr), tryptophan (Trp) and Acetaminophen (APAP), depending mainly on the matching degree of molecular dimensions between the analytes and the C4A cavity in addition to their chemical nature. More significantly, the film 1/ITO electrode shows a wide linear range of electrochemical detection (from 0.1 to 100 μM) to DA and APAP, with a high sensitivity of 53.0 and 94.3 μA mM-1 and a very low detection limit of 25 and 11 nM for DA and APAP, respectively, representing the best result among the nonenzymatic organic semiconductor-based biosensors. In particular, the film 1/ITO electrode exhibits excellent stability, reproducibility, high selectivity, and anti-interference nature for the detection of both DA and APAP, indicating the great potential of calix[n]arene macrocycle-modified tetrapyrrole rare earth sandwich compounds in the field of ultrasensitive and specific nonenzymatic sensors.


Acid leaching of LiCoO2 enhanced by reducing agent. Model formulation and validation.
In this work, a model has been formulated to describe the complex process of LiCoO2 leaching through the participation of competing reactions in acid media including the effect of H2O2 as reducing agent. The model presented here describes the extraction of Li and Co in the presence and absence of H2O2, and it takes into account the different phenomena affecting the controlling mechanisms. In this context, the model predicts the swift from kinetic control to diffusion control. The model has been implemented and solved to simulate the leaching process. To validate the model and to estimate the model parameters, a set of 12 (in triplicate) extraction experiments were carried out varying the concentration of hydrochloric acid (within the range of 0.5-2.5 M) and hydrogen peroxide (range 0-0.6%v/v). The simulation results match fairly well with the experimental data for a wide range of conditions. Furthermore, the model can be used to predict results with different solid-liquid ratios as well as different acid and oxygen peroxide concentrations. This model could be used to design or optimize a LiCoO2 extraction process facilitating the corresponding economical balance of the treatment.


Predictors of survival in coexistent hypersensitivity pneumonitis with autoimmune features.
Hypersensitivity pneumonitis (HP), an immune-mediated inflammatory interstitial lung disease (ILD), can result from exposure to several well-recognized antigens. Despite antigen avoidance, progressive pulmonary fibrosis and death can occur, suggesting that additional factors may contribute to disease activity. We hypothesized that the presence of autoimmunity might impact clinical course in patients with HP. In this study, we examined an HP cohort to identify those with HP and autoimmune features (HPAF), and determine its prevalence and outcomes. The University of Chicago ILD registry was screened to identify patients with HP. Patients were characterized as HPAF if they had an autoimmune disease or features of autoimmunity, defined as the presence of specific connective tissue disease (CTD) symptoms and serologies. Demographics, clinical characteristics, and outcomes were compared between groups. Survival analysis was performed using Cox regression to identify predictors of transplant-free survival in this cohort. One hundred twenty patients with chronic, fibrotic HP were identified. Of these, 18/120 (15%) were characterized as HPAF. Compared to those without evidence of autoimmunity, patients with HPAF had a higher proportion of females (54% vs. 83%, respectively; p = 0.02) but were otherwise similar with regard to clinical characteristics. The presence of autoimmunity was an independent predictor of increased mortality (HR 4.45; 95% CI 1.43-13.88; p = 0.01) after multivariable adjustment. Fifteen percent of patients with chronic, fibrotic HP displayed evidence of a concurrent defined autoimmune disease or autoimmune features suggestive of CTD. The presence of autoimmunity in patients with chronic, fibrotic HP may portend a poorer prognosis. Future studies are needed to validate these findings and determine the impact of immunosuppressive treatment.


Unobtrusive Refractive Power Monitoring: Using EOG to Detect Blurred Vision.
The rise in population and aging has led to a significant increase in the number of individuals affected by common causes of vision loss. Early diagnosis and treatment are crucial to avoid the consequences of visual impairment. However, in early stages, many visual problems are making it difficult to detect. Visual adaptation can compensate for several visual deficits with adaptive eye movements. These adaptive eye movements may serve as indicators of vision loss. In this work, we investigate the association between eye movement and blurred vision. By using Electrooculography (EOG) to record eye movements, we propose a new tracking model to identify the deterioration of refractive power. We verify the technical feasibility of this method by designing a blurred vision simulation experiment. Six sets of prescription lenses and a pair of flat lenses were used to create different levels of blurring effects. We analyzed binocular movements through EOG signals and performed a seven-class classification using the ResNet18 architecture. The results revealed an average classification accuracy of 94.7% in the subject-dependent model. However, the subject-independent model presented poor performance, with the highest accuracy reaching only 34.5%. Therefore, the potential of an EOG-based visual quality monitoring system is proven. Furthermore, our experimental design provides a novel approach to assessing blurred vision.


Adjuvanticity and protective immunity elicited by Leishmania donovani antigens encapsulated in positively charged liposomes.
In the search for a leishmaniasis vaccine, extensive studies of cutaneous leishmaniasis have been carried out. Investigations in this regard with the visceral form are limited. As an initial step in the identification of the protective molecules, leishmanial antigens extracted from the membranes of Leishmania donovani promastigotes, alone or in association with liposomes, were evaluated for their immunogenicity and ability to elicit a protective immune response against challenge infection. Intraperitoneal immunization of hamsters and BALB/c mice with the leishmanial antigens conferred protection against infection with the virulent promastigotes. Encapsulation in positively charged liposomes significantly enhanced the protective efficacy of these antigens. The splenic parasite burden of hamsters was reduced by 97% after 6 months of infection. BALB/c mice exhibited 87 and 81.3% protection in the liver and spleen, respectively, after 4 months of infection. These protected animals elicited profound delayed-type hypersensitivity and increased levels of Leishmania-specific immunoglobulin G (IgG) antibodies. Protection in mice also coincided with elevated levels of IgM and IgA antibodies, which decreased with disease progression in the control-infected animals. Although both IgG1 and IgG2a antibodies were present in the sera of infected mice, IgG1 appeared to be the predominant isotype, suggesting a preferential induction of the Th2 type of immune response over that of Th1. Effective stimulation of all the IgG isotypes, particularly IgG2a, after immunization with liposome encapsulated antigens seems to be responsible for the significant levels of resistance against the disease. Taken together, these data indicate a potential for the liposomal antigens as a vaccine which could trigger both humoral and cell-mediated immune responses.


Adaptation of cardiac morphology and function to endurance and strength training. A comparative study using MR imaging and echocardiography in males and females.
Left ventricular (LV) dimensions and function and maximal oxygen uptake (VO(2)max) were measured in endurance-trained (10 male, m, 10 female, f), strength-trained athletes (8 m, 10 f) and untrained subjects (9 m, 10 f). LV dimensions were measured using magnetic resonance imaging (MRI) and echocardiography and the results were equal irrespective of method. Endurance-trained m and f had significantly higher LV volumes and mass than both strength-trained and controls. No VO(2)max or dimensional differences were seen between strength-trained and untrained subjects. In endurance-trained males, LV volumes and mass/kg bw were higher than in endurance-trained females. There was no significant gender difference for strength-trained or untrained subjects regarding body weight-related heart dimensions. It is concluded that LV dimensions and volumes are strongly dependent on oxygen transport capacity in normal subjects practising different modes of training, and that the gender differences, if LV dimensions are related to aerobic work capacity, are smaller than previously reported.


The potential role of photoelectron microscopy in the analysis of biological surfaces.
The photoelectric effect provides the basis for an imaging technique useful for the study of biological surfaces. The photoelectron microscope (PEM) employs a UV lamp to photoeject electrons from the specimen surface. The electrons are then accelerated and imaged using electron optics. Photoelectron micrographs often resemble scanning electron micrographs, but the origin of contrast is different and these two techniques are complementary. Scanning Electron Microscopy (SEM) is unsurpassed in applications where specimens have pronounced relief or where elemental analysis is required. The advantages of PEM are a new origin of contrast, high sensitivity to fine topographical detail, short depth of information, and low specimen conductivity requirements. Photoelectron images of model systems, cell surfaces and cytoskeletal elements have been obtained.


Screening ECGs for young competitive athletes: it is complicated.
The role of the ECG in preparticipation sports screening for adolescent athletes is a major area of controversy today. Sudden cardiac death, especially in a young seemingly healthy individual, is a tragic and highly publicized event, which is often surrounded by cries from the public and medical community to 'do something.' This emotional need to address these catastrophic events has led to over 4000 articles addressing the optimal way to screen the young athlete, as well as conflicting recommendations from the American Heart Association and the European Society of Cardiology, specifically in regards to inclusion of a screening ECG. This article will review the advances in the field over the last year, including the new guidelines on screening of the young athlete from the American Heart Association. This last year has seen several important additions to the controversy surrounding the use of the 12-lead ECG in the screening of the young athlete. Although improved ECG criteria have decreased the prevalence of false positives, the actual utility of this practice has not been tested in real clinical practice outside of a formal investigation.


Soil properties constrain predicted poleward migration of plants under climate change.
Many plant species are predicted to migrate poleward in response to climate change. Species distribution models (SDMs) have been widely used to quantify future suitable habitats, but they often neglect soil properties, despite the importance of soil for plant fitness. As soil properties often change along latitudinal gradients, higher-latitude soils might be more or less suitable than average conditions within the current ranges of species, thereby accelerating or slowing potential poleward migration. In this study, we built three SDMs - one with only climate predictors, one with only soil predictors, and one with both - for each of 1870 plant species in Eastern North America, in order to investigate the relative importance of soil properties in determining plant distributions and poleward shifts under climate change. While climate variables were the most important predictors, soil properties also had a substantial influence on continental-scale plant distributions. Under future climate scenarios, models including soil predicted much smaller northward shifts in distributions than climate-only models (c. 40% reduction). Our findings strongly suggest that high-latitude soils are likely to impede ongoing plant migration, and they highlight the necessity of incorporating soil properties into models and predictions for plant distributions and migration under environmental change.


What determines prey selection in owls? Roles of prey traits, prey class, environmental variables, and taxonomic specialization.
Ecological theory suggests that prey size should increase with predator size, but this trend may be masked by other factors affecting prey selection, such as environmental constraints or specific prey preferences of predator species. Owls are an ideal case study for exploring how predator body size affects prey selection in the presence of other factors due to the ease of analyzing their diets from owl pellets and their widespread distributions, allowing interspecific comparisons between variable habitats. Here, we analyze various dimensions of prey resource selection among owls, including prey size, taxonomy (i.e., whether or not particular taxa are favored regardless of their size), and prey traits (movement type, social structure, activity pattern, and diet). We collected pellets of five sympatric owl species (Athene noctua, Tyto alba, Asio otus, Strix aluco, and Bubo bubo) from 78 sites across the Mediterranean Levant. Prey intake was compared between sites, with various environmental variables and owl species as predictors of abundance. Despite significant environmental impacts on prey intake, some key patterns emerge among owl species studied. Owls select prey by predator body size: Larger owls tend to feed on wider ranges of prey sizes, leading to higher means. In addition, guild members show both specialization and generalism in terms of prey taxa, sometimes in contrast with the expectations of the predator-prey body size hypothesis. Our results suggest that while predator body size is an important factor in prey selection, taxon specialization by predator species also has considerable impact.


Could immediate second-look endoscopy reduce post-endoscopic submucosal dissection bleeding?
Gastric endoscopic submucosal dissection (ESD) is a curative treatment for gastric neoplasm. A scheduled second-look endoscopy could be performed to prevent delayed post-ESD bleeding. However, no studies on the efficacy of second-look endoscopy for the prevention of early delayed post-ESD bleeding have been conducted. So, the aim of this study was to be the first to investigate the efficacy of immediate second-look endoscopy for the prevention of post-ESD bleeding. The 266 gastric ESD cases were included. Immediate second-look endoscopy was defined as repeated upper endoscopy soon after complete hemostasis of the ESD site and specimen fixation. Early and late delayed bleeding were classified as before or after 24 h after the ESD, respectively. The 262 ESD cases were enrolled and divided into three groups: the immediate second-look (n = 79), scheduled second-look (n = 86), and no second-look (n = 97). Post-ESD bleeding occurred in 19 cases (7.3%). Of these, 13 (68.4%) were early delayed post-ESD bleeding. The immediate second-look endoscopy had a lower incidence of early delayed post-ESD bleeding compared to the groups without immediate second-look endoscopy, (3.8% vs. 0.8%, p = 0.009). In a multivariate analysis, immediate second-look endoscopy significantly reduced early delayed post-ESD bleeding (OR 0.39, p = 0.022). The resected specimen area ≥ 1,000 mm2 was an independent risk factor for early delayed post-ESD bleeding (OR 8.98, p = 0.010). However, the frequency of delayed post-ESD bleeding did not differ between the three groups. Immediate second-look endoscopy after gastric ESD may prevent early delayed post-ESD bleeding under certain circumstances.


GABA(A) receptor epsilon and theta subunits display unusual structural variation between species and are enriched in the rat locus ceruleus.
Previously, GABA(A) receptor epsilon and theta subunits have been identified only in human. Here, we describe properties of the epsilon and theta subunit genes from mouse and rat that reveal an unusually high level of divergence from their human homologs. In addition to a low level of amino acid sequence conservation ( approximately 70%), the rodent epsilon subunit cDNAs encode a unique Pro/Glx motif of approximately 400 residues within the N-terminal extracellular domain of the subunits. Transcripts of the rat epsilon subunit were detected in brain and heart, whereas the mouse theta subunit mRNA was detectable in brain, lung, and spleen by Northern blot analysis. In situ hybridization revealed a particularly strong signal for both subunit mRNAs in rat locus ceruleus in which expression was detectable from the first postnatal day. Lower levels of coexpression were also detected in other brainstem nuclei and in the hypothalamus. However, the expression pattern of theta subunit mRNA was more widespread than that of epsilon subunit, being found also in the cerebral cortex of rat pups. In contrast to primate brain, neither subunit was expressed in the hippocampus or substantia nigra. The results indicate that GABA(A) receptor epsilon and theta subunits are evolving at a much faster rate than other known GABA(A) receptor subunits and that their expression patterns and functional properties may differ significantly between species.


Three-dimensional electroactive ZnO nanomesh directly derived from hierarchically self-assembled block copolymer thin films.
Three-dimensional (3D) nanoarchitectures can offer enhanced material properties, such as large surface areas that amplify the structures' interaction with environments making them useful for various sensing applications. Self-assembled block copolymers (BCPs) can readily generate various 3D nanomorphologies, but their conversion to useful inorganic materials remains one of the critical challenges against the practical application of self-assembled BCPs. This work reports the vapor-phase infiltration synthesis of optoelectrically active, 3D ZnO nanomesh architectures by combining hierarchical successive stacking of self-assembled, lamellar-phase polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) BCP thin films and a modified block-selective vapor-phase material infiltration protocol. The 3D ZnO nanomesh exhibits optoelectrical functionality, featuring stack-layer-number-dependent electrical conductance resembling the percolative transport originating from the intrinsic morphological network connectivity of the lamellar BCP pattern with symmetric block ratio. The results not only illustrate the first demonstration of electrical functionality based on the ZnO nanoarchitecture directly generated by the infiltration synthesis in self-assembled BCP thin films but also present a new, large-area scalable, metal oxide thin film nanoarchitecture fabrication method utilizing industry-compatible polymer solution coating and atomic layer deposition. Given the large surface area, three-dimensional porosity, and readily scalable fabrication procedures, the generated ZnO nanomesh promises potential applications as an efficient active medium in chemical and optical sensors.


Cohort profile: demographic and clinical characteristics of the MILESTONE longitudinal cohort of young people approaching the upper age limit of their child mental health care service in Europe.
The presence of distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) impacts continuity of mental health treatment for young people. However, we do not know the extent of discontinuity of care in Europe nor the effects of discontinuity on the mental health of young people. Current research is limited, as the majority of existing studies are retrospective, based on small samples or used non-standardised information from medical records. The MILESTONE prospective cohort study aims to examine associations between service use, mental health and other outcomes over 24 months, using information from self, parent and clinician reports. Seven hundred sixty-three young people from 39 CAMHS in 8 European countries, their parents and CAMHS clinicians who completed interviews and online questionnaires and were followed up for 2 years after reaching the upper age limit of the CAMHS they receive treatment at. This cohort profile describes the baseline characteristics of the MILESTONE cohort. The mental health of young people reaching the upper age limit of their CAMHS varied greatly in type and severity: 32.8% of young people reported clinical levels of self-reported problems and 18.6% were rated to be 'markedly ill', 'severely ill' or 'among the most extremely ill' by their clinician. Fifty-seven per cent of young people reported psychotropic medication use in the previous half year. Analysis of longitudinal data from the MILESTONE cohort will be used to assess relationships between the demographic and clinical characteristics of young people reaching the upper age limit of their CAMHS and the type of care the young person uses over the next 2 years, such as whether the young person transitions to AMHS. At 2 years follow-up, the mental health outcomes of young people following different care pathways will be compared. NCT03013595.


Challenges facing the farm animal veterinary profession in England: A qualitative study of veterinarians' perceptions and responses.
The farm animal veterinary profession in the UK has faced a number of challenges in recent decades related to the withdrawal of government funding and a contraction of the agricultural sector. They have come under pressure to respond by developing skills and focusing on disease prevention advisory services. However, this puts veterinarians in competition with other providers of these services, and moves in this direction have only been partial. Failure to respond to these challenges puts the veterinary profession at risk of de-professionalisation-a loss of their monopoly over knowledge, an erosion of client beliefs in their service ethos and a loss of work autonomy. This paper explores how farm animal veterinarians in England perceive these challenges and are responding to them. Semi-structured qualitative interviews were carried out with 28 veterinarians from Royal College of Veterinary Surgeon farm accredited practices. Veterinarians were chosen from high, medium and low density cattle farming regions. Interviews were recorded, transcribed and themes identified through the constant comparison method. The majority of respondents recognised the challenges facing the veterinary profession. Most believed their role had changed, moving towards that of a disease prevention adviser who was part of the farm management team. In terms of maintaining and redefining their professional status, farm animal veterinarians do have a defined body of knowledge and the ability to develop trusting relationships with clients, which enhances their competitiveness. However, while they recognise the changes and challenges, moves towards a disease prevention advisory model have only been partial. There seem to be little effort towards using Farm accreditation status or other strategies to promote their services. They do not appear to be finding effective strategies for putting their knowledge on disease prevention into practice. Disease prevention appears to be delivered on farm on an ad hoc basis, they are not promoting their disease prevention services to farmers effectively or using their professional position to stave off competition. Farm animals veterinarians will need to realign their veterinary expertise to the demands of the market, work together rather than in competition, improve their skills in preventive medicine, consolidate information given by non-veterinary advisors, develop new business models appropriate to their services and develop entrepreneurial skills to demonstrate their market value if they are to avoid becoming marginalised.


An unnatural amino acid that induces beta-sheet folding and interaction in peptides.
This paper introduces a unique amino acid that can readily be incorporated into peptides to make them fold into beta-sheetlike structures that dimerize through beta-sheet interactions. This new amino acid, Orn(i-PrCO-Hao), consists of an ornithine residue with the beta-strand-mimicking amino acid Hao [J. Am. Chem. Soc. 2000, 122, 7654-7661] attached to its side chain. When Orn(i-PrCO-Hao) is incorporated into a peptide, or appended to its N-terminus, the Hao group hydrogen bonds to the three subsequent residues to form a beta-sheetlike structure. The amino acid Orn(i-PrCO-Hao) is readily used in peptide synthesis as its Fmoc derivative, Fmoc-Orn(i-PrCO-Hao)-OH (3). Fmoc-Orn(i-PrCO-Hao)-OH behaves like a regular amino acid in peptide synthesis and was uneventfully incorporated into the peptide o-anisoyl-Val-Orn(i-PrCO-Hao)-Phe-Ile-Leu-NHMe (4) through standard automated Fmoc solid-phase peptide synthesis, with DIC and HOAt as the coupling agent for Fmoc-Orn(i-PrCO-Hao)-OH and o-anisic acid and HATU as the coupling agent for all other couplings. A second synthetic strategy was developed to facilitate the preparation of peptides with N-terminal Orn(i-PrCO-Hao) residues, which avoids the need for the preparation of Fmoc-Orn(i-PrCO-Hao)-OH. In this strategy, Boc-Orn(Fmoc)-OH is used as the penultimate amino acid in the peptide synthesis, and i-PrCO-Hao-OH (2) is used as the final amino acid. N-Terminal Orn(i-PrCO-Hao) peptide H-Orn(i-PrCO-Hao)-Phe-Ile-Leu-NHMe.TFA (5) was prepared in a fashion similar to that for 4, using DIC and HOAt as the coupling agent for i-PrCO-Hao-OH and HATU as the coupling agent for all other couplings. 1H NMR transverse-ROESY, coupling constant, and chemical shift studies establish that peptide 4 forms a dimeric beta-sheetlike structure in CDCl3 solution. The 1H NMR studies also suggest that the ornithine unit adopts a well-defined turn conformation. Analogous 1H NMR studies of peptide 5 indicate that this TFA salt folds but does not dimerize in CD3OD solution. Collectively, these synthetic and spectroscopic studies establish that the amino acid Orn(i-PrCO-Hao) induces beta-sheet structure and interactions in peptides in suitable organic solvents. Unlike the Hao amino acid, which acts as a prosthetic to replace three residues of the peptide strand, the Orn(i-PrCO-Hao) amino acid acts as a splint that helps enforce a beta-sheetlike structure without replacing the residues and their side chains. This feature of Orn(i-PrCO-Hao) is important, because it allows the creation of beta-sheet structure with minimal perturbation of the peptide sequence.


Virology and immune mechanisms.
Epstein-Barr virus and hepatitis B virus are two agents which chronically infect man and have been associated with specific neoplasms. Such findings point the way to new methods of control and detection of human malignancies. Furthermore, immunosuppression is another major factor underlying the development of certain malignancies in human populations. It is clear that congenital immunodeficiency states as well as organ transplant recipients requiring iatrogenic immunosuppression and cancer patients requiring chemotherapy and/or x-irradiation are susceptible to particular malignancies at a higher rate than the normal population. Such findings also provide not only clues as to the mechanisms which control tumor development but argue for certain limitations to the extent of immunosuppressive therapy utilized for treatment of cancer.


Poretools: a toolkit for analyzing nanopore sequence data.
Nanopore sequencing may be the next disruptive technology in genomics, owing to its ability to detect single DNA molecules without prior amplification, lack of reliance on expensive optical components, and the ability to sequence long fragments. The MinION™ from Oxford Nanopore Technologies (ONT) is the first nanopore sequencer to be commercialized and is now available to early-access users. The MinION™ is a USB-connected, portable nanopore sequencer that permits real-time analysis of streaming event data. Currently, the research community lacks a standardized toolkit for the analysis of nanopore datasets. We introduce poretools, a flexible toolkit for exploring datasets generated by nanopore sequencing devices from MinION™ for the purposes of quality control and downstream analysis. Poretools operates directly on the native FAST5 (an application of the HDF5 standard) file format produced by ONT and provides a wealth of format conversion utilities and data exploration and visualization tools. Poretools is an open-source software and is written in Python as both a suite of command line utilities and a Python application programming interface. Source code is freely available in Github at https://www.github.com/arq5x/poretools.


Stop-flow in mediastinum and thorax for resistant lymphoma.
Management of patients with heavily pretreated malignant lymphoma failing frontline treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue, is problematic. A pilot study was conducted to evaluate isolated thoracic perfusion of drugs by means of stopflow technique. Six patients were enrolled in the study; diagnoses included 4 advanced Hodgkin's disease, 1 primary mediastinal B-cell lymphoma, and 1 anaplastic large cell lymphoma. Patients were aged 18-37 years; 4 presented with bulky mediastinum. They had never achieved a complete response since all had progressed from front-line treatment, and 3 had even failed salvage high-dose chemotherapy with autologous peripheral stem cell rescue. Cisplatin (100 mg/m2) and melphalan (35 mg/m2) were used. Carmustine (100 mg/m2) were added to these 2 drugs and cytarabine (2000 mg/m2) in patients not previously treated by carmustine, etoposide, cytarabine, and melphalan. Epidoxorubicin (70 mg/m2) was added in patients who previously received a suboptimal dosage of antracycline. Drugs were delivered monthly via aortic perfusion performed by means of Aigner's stop-flow technique. Overall 13 cycles of perfusional chemotherapy were administered with a median number of 2 cycles. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. After 1 month, 6 (100%) objective responses after isolated thoracic perfusion were recorded, 3 (50%) of which were complete. Tolerance to therapy was excellent. Hematological toxicity was mild and transfusional support was needed only in one course. At the last follow-up, 2 patients are alive (1 complete response and 1 very good partial response, maintained). This new therapeutical approach seems very active in recurrent/refractory malignant lymphoma and may play an important role in this setting.


Dampening of population cycles in voles affects small mammal community structure, decreases diversity, and increases prevalence of a zoonotic disease.
Long-term decline and depression of density in cyclic small rodents is a recent widespread phenomenon. These observed changes at the population level might have cascading effects at the ecosystem level. Here, we assessed relationships between changing boreal landscapes and biodiversity changes of small mammal communities. We also inferred potential effects of observed community changes for increased transmission risk of Puumala virus (PUUV) spread, causing the zoonotic disease nephropatica epidemica in humans. Analyses were based on long-term (1971-2013) monitoring data of shrews and voles representing 58 time series in northern Sweden. We calculated richness, diversity, and evenness at alpha, beta, and gamma level, partitioned beta diversity into turnover (species replacement) and nestedness (species addition/removal), used similarity percentages (SIMPER) analysis to assess community structure, and calculated the cumulated number of PUUV-infected bank voles and average PUUV prevalence (percentage of infected bank voles) per vole cycle. Alpha, beta, and gamma richness and diversity of voles, but not shrews, showed long-term trends that varied spatially. The observed patterns were associated with an increase in community contribution of bank vole (Myodes glareolus), a decrease of gray-sided vole (M. rufocanus) and field vole (Microtus agrestis) and a hump-shaped variation in contribution of common shrew (Sorex araneus). Long-term biodiversity changes were largely related to changes in forest landscape structure. Number of PUUV-infected bank voles in spring was negatively related to beta and gamma diversity, and positively related to turnover of shrews (replaced by voles) and to community contribution of bank voles. The latter was also positively related to average PUUV prevalence in spring. We showed that long-term changes in the boreal landscape contributed to explain the decrease in biodiversity and the change in structure of small mammal communities. In addition, our results suggest decrease in small mammal diversity to have knock-on effects on dynamics of infectious diseases among small mammals with potential implications for disease transmission to humans.


Ischemic stroke hospital admission associated with ambient temperature in Jinan, China.
This study estimated the effects of ambient temperature and relative humidity on hospital admissions for ischemic stroke during 1990-2009 in Jinan, China. To account for possible delayed effects and harvesting effect, we examined the impact of meteorological factors up to 30 days before each admission using a distributed lag non-linear model; we controlled for season, long-term trend, day of week and public holidays in the analysis. Stratified analyses were also done for summer and winter. A total of 1,908 ischemic stroke hospital admissions were observed between 1990 and 2009. We found a strong non-linear acute effect of daily temperatures on ischemic stroke hospital admission. With the mean temperature 15°C as the reference, the relative risk (RR) was 1.43 (95% confidence interval (CI): 1.10-1.85) for 0°C daily temperature on the same day, and 0.43 (95% CI: 0.31-0.59) for 30°C daily temperature on the same day, respectively. The effect of ambient temperature was similar in summer and winter. No significant association was observed between relative humidity and ischemic stroke hospitalization. Low temperature might be a risk factor for ischemic stroke, and high temperature might be protective factor of ischemic stroke occurrence in Jinan, China.


Near-infrared light to aid peripheral intravenous cannulation in children: a cluster randomised clinical trial of three devices.
Intravenous cannulation can be difficult in children. Recently, new devices using near-infrared light to make blood vessels visible have become available. We aimed to evaluate the effectiveness of three such devices in facilitating peripheral intravenous cannulation in children. In this cluster randomised clinical trial, daily operating rooms at a tertiary childrens' hospital were randomised to the use of the VeinViewer®, AccuVein® AV300, VascuLuminator Vision® or to a control group. We included 1913 children between birth and 18 years scheduled for elective surgery. Suitable veins for cannulation were more easily visible with the VeinViewer (307/322 (95.3%)) and AccuVein (239/254 (94.1%)) devices than with VascuLuminator (229/257 (89.1%)) (p = 0.03). However, success at the first attempt was not significantly different among groups, ranging from 73.1% to 75.3% (p = 0.93). We conclude that although vein visibility is enhanced, near-infrared devices do not improve cannulation.


Beneficial effect of two culture systems with small groups of embryos on the development and quality of in vitro-produced bovine embryos.
Currently, in vitro-produced embryos derived by ovum pick up (OPU) and in vitro fertilization (IVF) technologies represent approximately one-third of the embryos worldwide in cattle. Nevertheless, the culture of small groups of embryos from an individual egg donor is an issue that OPU-IVF laboratories have to face. In this work, we tested whether the development and quality of the preimplantation embryos in vitro cultured in low numbers (five embryos) could be improved by the addition of epidermal growth factor, insulin, transferrin and selenium (EGF-ITS) or by the WOW system. With this aim, immature oocytes recovered from slaughtered heifers were in vitro matured and in vitro fertilized. Presumptive zygotes were then randomly cultured in four culture conditions: one large group (LG) (50 embryos/500 μl medium) and three smaller groups [five embryos/50 μl medium without (control) or with EGF-ITS (EGF-ITS) and five embryos per microwell in the WOW system (WOW)]. Embryos cultured in LG showed a greater ability to develop to blastocyst stage than embryos cultured in smaller groups, while the blastocyst rate of WOW group was significantly higher than in control. The number of cells/blastocyst in LG was higher than control or WOW, whereas the apoptosis rate per blastocyst was lower. On the other hand, the addition of EGF-ITS significantly improved both parameters compared to the control and resulted in similar embryo quality to LG. In conclusion, the WOW system improved embryo development, while the addition of EGF-ITS improved the embryo quality when smaller groups of embryos were cultured.


Comparison of primer sets for the study of Planctomycetes communities in lentic freshwater ecosystems.
In search of a primer set that could be used to study Planctomycetes dynamics in lakes and especially via fingerprinting methods, e.g. denaturing gradient gel electrophoresis (DGGE), three existing specific primer sets, developed for marine and soil systems, have been tested on water samples from four freshwater ecosystems. The first primer set (PLA46F/PLA886R) allowed PCR amplification of Planctomycetes sequences in only one of the four ecosystems, whereas the second primer set (PLA40F/P518R) amplified Planctomycetes sequences in all the studied ecosystems but with a low specificity, since sequences belonging to Verrucomicrobiales and Chlamydiales clades were also amplified. Finally, the third primer set (PLA352F/PLA920R) allowed amplification of Planctomycetes sequences in the four ecosystems with a very high specificity. It amplified all known Planctomycetes genera and yielded the highest Operational Taxonomic Unit (OTU) richness and diversity estimates. In silico analyses supported these results. Further experiments comparing PLA352F/PLA920R to PLA46F/P1390R (a primer set generating a longer PCR fragment, also used to study Planctomycetes) yielded very similar results. Our findings suggest that the primer set PLA352F/PLA920R provides good estimates of Planctomycetes richness and diversity compared with other, and can thus be used to study Planctomycetes dynamics in lentic freshwater ecosystems.


Monitoring and responding to signals of suicidal ideation in pragmatic clinical trials: Lessons from the GRACE trial for Chronic Sickle Cell Disease Pain.
Sickle cell disease (SCD) is a hemoglobin disorder and the most common genetic disorder that affects 100,000 Americans and millions worldwide. Adults living with SCD have pain so severe that it often requires opioids to keep it in control. Depression is a major global public health concern associated with an increased risk in chronic medical disorders, including in adults living with sickle cell disease (SCD). A strong relationship exists between suicidal ideation, suicide attempts, and depression. Researchers enrolling adults living with SCD in pragmatic clinical trials are obligated to design their methods to deliberately monitor and respond to symptoms related to depression and suicidal ideation. This will offer increased protection for their participants and help clinical investigators meet their fiduciary duties. This article presents a review of this sociotechnical milieu that highlights, analyzes, and offers recommendations to address ethical considerations in the development of protocols, procedures, and monitoring activities related to suicidality in depressed patients in a pragmatic clinical trial.


Advanced Methods for Accessing Protein Shape-Shifting Present New Therapeutic Opportunities.
A protein is a dynamic shape-shifter whose function is determined by the set of structures it adopts. Unfortunately, atomically detailed structures are only available for a few conformations of any given protein, and these structures have limited explanatory and predictive power. Here, we provide a brief historical perspective on protein dynamics and introduce recent advances in computational and experimental methods that are providing unprecedented access to protein shape-shifting. Next, we focus on how these tools are revealing the mechanism of allosteric communication and features like cryptic pockets; both of which present new therapeutic opportunities. A major theme is the importance of considering the relative probabilities of different structures and the control one can exert over protein function by modulating this balance.


Obesity potentially protects against systemic bone loss in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors.
We aimed to investigate how systemic bone metabolism was affected after 1 year of treatment with tumour necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients. A total of 29 seropositive RA patients not treated for osteoporosis were enrolled and TNF inhibitors were administered for a year. Bone mineral density (BMD) at the lumbar spine, femur neck, and total hip was measured at baseline and 12 months after anti-TNF treatment. Blood samples were collected at baseline and 6 and 12 months after anti-TNF treatment and osteoclasts were cultured on bone slices. Weight was the strongest factor influencing systemic bone loss. Patients were categorised into two groups: obese (body mass index (BMI) ≥25 kg/m2) and non-obese (BMI <25 kg/m2). All patients showed decreased BMD at all sites. The obese group showed relatively little change in BMD, although the non-obese group showed significant decreases in BMD at all sites after 1 year of treatment with TNF inhibitors. Resorption pits created by osteoclasts decreased at 6 months and increased at 12 months in the non-obese group, while the obese group presented with steadily decreasing sizes of resorption pits at all-time points. Levels of receptor activator of nuclear factor kappa B ligand were significantly decreased at 12 months compared to baseline in the obese group, while they were increased in the non-obese group. One year of treatment with TNF inhibitors failed to halt systemic bone loss in RA patients, but obesity may have protective effects against bone loss.


Development of protease activation mutants of HVJ (Sendai virus) in persistently infected cell cultures.
HVJ wild-type virus, in which the F protein is activated by trypsin but not by elastase, was spontaneously converted to a mutant with an F protein characterized by being activated by elastase alone. This spontaneous mutation generally occurred during serial passages of cells persistently infected with HVJ, even though the cells were first established by infection with plaque-purified wild-type virus. Multiple-cycle replication, plaque formation, haemolysis and SDS-polyacrylamide gel electrophoretic (SDS-PAGE) analysis showed that all the elastase-activated mutants isolated from HVJ carrier cells no longer required trypsin for F protein activation. At early passages, these protease activation mutants did not show temperature-sensitive (ts) growth, while at a later stage the mutants, together with the ts mutation, appeared dominant. The frequency of such a protease activation mutation during passage in the HVJ carrier cells seemed to depend on the cell species, but was increased when compared to lytic infections.