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Background Hospital-acquired influenza virus infection (HAII) can cause severe morbidity and mortality. Identifying potential transmission routes can inform prevention strategies. Methods We identified all hospitalized patients testing positive for influenza A virus at a large, tertiary care hospital during the 2017–2018 and 2019–2020 influenza seasons. Hospital admission dates, locations of inpatient service, and clinical influenza testing information were retrieved from the electronic medical record. Time-location groups of epidemiologically linked influenza patients were defined and contained ≥1 presumed HAII case (first positive ≥48 hours after admission). Genetic relatedness within time-location groups was assessed by whole genome sequencing. Results During the 2017–2018 season, 230 patients tested positive for influenza A(H3N2) or unsubtyped influenza A including 26 HAIIs. There were 159 influenza A(H1N1)pdm09 or unsubtyped influenza A–positive patients identified during the 2019–2020 season including 33 HAIIs. Consensus sequences were obtained for 177 (77%) and 57 (36%) of influenza A cases in 2017–2018 and 2019–2020, respectively. Among all influenza A cases, there were 10 time-location groups identified in 2017–2018 and 13 in 2019–2020; 19 of 23 groups included ≤4 patients. In 2017–2018, 6 of 10 groups had ≥2 patients with sequence data, including ≥1 HAII case. Two of 13 groups met this criteria in 2019–2020. Two time-location groups from 2017–2018 each contained 3 genetically linked cases. Conclusions Our results suggest that HAIIs arise from outbreak transmission from nosocomial sources as well as single infections from unique community introductions. [ABSTRACT FROM AUTHOR]

1988, the World Health Assembly committed to eradicate poliomyelitis, a viral disease that can cause permanent paralysis. Today, only type 1 of the three wild poliovirus types remains circulating in limited geographic areas following widespread use of different poliovirus vaccines. While we are close to zero new cases of wild polio, it is a fragile situation, and there are many remaining and new hurdles to overcome. Here, experts discuss how to address them. [ABSTRACT FROM AUTHOR]

When first approved, many hoped that the SARS-CoV-2 vaccine would provide long-term protection after a primary series. Waning of immunity and continued appearance of new variants has made booster inoculations necessary. The process is becoming increasingly similar to that used for annual updating of the influenza vaccine. The similarity has become even more apparent with selection of BA.4/BA.5 as the Omicron strain of the updated bivalent (Original + Omicron) Covid-19 vaccines. It is hoped that, if Covid-19 develops winter seasonality, SARS-CoV-2 vaccines will require only annual review to determine if updates are necessary. Recommendations on whom should receive the booster would be based on conditions at that time. [ABSTRACT FROM AUTHOR]

Context.--Next-generation sequencing is a powerful clinical tool for cancer management but can produce incidental/secondary findings that require special consideration. Objective.--To discuss clinical and laboratory issues related to incidental or secondary germline findings in the clinical setting of tumor testing and inform future guidelines in this area. Design.--A College of American Pathologists workgroup including representation from the American Society of Clinical Oncology, the Association for Molecular Pathology, and the American College of Medical Genetics and Genomics created a review of items that should be considered when developing guidelines for incidental or secondary findings when performing clinical tumor testing. Results.--Testing recommendations should be cognizant of the differences among anticipated incidental, unanticipated incidental, and secondary findings, and whether normal tissue is also tested. In addition to defining which variants will be reported, robust recommendations must also take into account test design and validation, reimbursement, cost, infrastructure, impact on reflex testing, and maintenance of proficiency. Care providers need to consider the potential of a test to uncover incidental or secondary findings, the recommendation of upfront counseling, the need for consent, the timing of testing and counseling, and that the exact significance of a finding may not be clear. Conclusions.--As clinical oncology testing panels have become a mainstay of clinical cancer care, guidelines addressing the unique aspects of incidental and secondary findings in oncology testing are needed. This paper highlights clinical and laboratory considerations with regard to incidental/secondary findings and is a clarion call to create recommendations. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies targeting the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 spike protein are important outpatient treatment options in coronavirus disease 2019 to mitigate progression of disease and prevent hospitalization. The impact of different RBD mutations on the efficacy of the available monoclonal antibodies and processes for incorporating this impact into treatment algorithms are ill defined. Herein, we synthesize the data surrounding the impact of key RBD mutations on the efficacy of US Food and Drug Administration Emergency Use Authorized monoclonal antibodies and describe our approach at Michigan Medicine at monitoring mutation frequency in circulating virus and developing an algorithm that incorporates these data into outpatient treatment pathways. [ABSTRACT FROM AUTHOR]

B cells undergoing physiologically programmed or aberrant genomic alterations provide an opportune system to study the causes and consequences of genome mutagenesis. Activated B cells in germinal centers express activation-induced cytidine deaminase (AID) to accomplish physiological somatic hypermutation (SHM) of their antibody-encoding genes. In attempting to diversify their immunoglobulin (Ig) heavy- and light-chain genes, several B-cell clones successfully optimize their antigen-binding affinities. However, SHM can sometimes occur at non-Ig loci, causing genetic alternations that lay the foundation for lymphomagenesis, particularly diffuse large B-cell lymphoma. Thus, SHM acts as a double-edged sword, bestowing superb humoral immunity at the potential risk of initiating disease. We refer to off-target, non-Ig AID mutations — that are often but not always associated with disease — as aberrant SHM (aSHM). A key challenge in understanding SHM and aSHM is determining how AID targets and mutates specific DNA sequences in the Ig loci to generate antibody diversity and non-Ig genes to initiate lymphomagenesis. Herein, we discuss some current advances regarding the regulation of AID's DNA mutagenesis activity in B cells. • In B cells, AID is responsible for the physiological hypermutation of the immunoglobulin locus. • AID is also responsible for the aberrant hypermutation of off-target loci. • Aberrant hypermutation by AID in noncoding regions is seen in lymphomagenesis and lymphoma transformation. • Recent work on DNA flexibility, enhancers, and chromatin architecture begins to uncover how AID is normally and aberrantly targeted. [ABSTRACT FROM AUTHOR]

Hospital-associated respiratory virus infections (HARVI) are an underappreciated source of morbidity and mortality. We examined HARVI incidence and clinical respiratory virus testing practices in a cohort of hospitalized patients with acute respiratory illness. HARVI were identified in patients of all ages, both during and outside of the influenza season. [ABSTRACT FROM AUTHOR]

Highlights • Case evidence suggests PD may lead to interest, creativity, change in produced art. • Occurs in both established artists and those without prior desire toward art making. • We review case evidence and relate to current knowledge on PD symptoms/neurobiology. • Propose hypothesis of selective damage + agonist overstimulation of mesolimbic areas. • Also relate to context, personality, genetic differences offering window into artistic brain. Abstract Parkinson's disease (PD) is a devastating diagnosis with, however, potential for an extremely intriguing aesthetic component. Despite motor and cognitive deficits, an emerging collection of studies report a burst of visual artistic output and alterations in produced art in a subgroup of patients. This provides a unique window into the neurophysiological bases for why and how we might create and enjoy visual art, as well as into general brain function and the nature of PD or other neurodegenerative diseases. However, there has not been a comprehensive organization of literature on this topic. Nor has there been an attempt to connect case evidence and knowledge on PD with present understanding of visual art making in psychology and neuroaesthetics in order to propose hypotheses for documented artistic changes. Here, we collect the current research on this topic, tie this to PD symptoms and neurobiology, and provide new theories focusing on dopaminergic neuron damage, over-stimulation from dopamine agonist therapy, and context or genetic factors revealing the neurobiological basis of the visual artistic brain. [ABSTRACT FROM AUTHOR]

This Viewpoint discusses emerging genetic variants of SARS-CoV-2, including new "UK" and "mink" variants and the significance of the new variants to coronavirus transmissibility, spread, virulence, and efforts to vaccinate the population against COVID-19. [ABSTRACT FROM AUTHOR]

Many viruses evolve rapidly. This is due, in part, to their high mutation rates. Mutation rate estimates for over 25 viruses are currently available. Here, we review the population genetics of virus mutation rates. We specifically cover the topics of mutation rate estimation, the forces that drive the evolution of mutation rates, and how the optimal mutation rate can be context-dependent. [ABSTRACT FROM AUTHOR]

Objective: To compare healthcare utilization and outcomes using the Carpenter-Coustan (CC) criteria vs. the National Diabetes Data Group (NDDG) criteria for gestational diabetes mellitus (GDM). Methods: This is a retrospective cohort study. Prior to 8/21/2013, patients were classified as "GDM by CC" if they met criteria. After 8/21/2013, patients were classified as "GDM by NDDG" if they met criteria and "Meeting CC non-GDM" if they met CC, but failed to reach NDDG criteria. "Non-GDM" women did not meet any criteria for GDM. Records were reviewed after delivery. Results: There was a 41% reduction in GDM diagnosed using NDDG compared to CC (P=0.01). There was no significant difference in triage visits, ultrasounds for growth or hospital admissions. Women classified as "Meeting CC non-GDM" were more likely to have preeclampsia than "GDM by CC" women [OR 11.11 (2.7, 50.0), P=0.0006]. Newborns of mothers "Meeting CC non-GDM" were more likely to be admitted to neonatal intensive care units than "GDM by CC" [OR 6.25 (1.7, 33.3), P=0.006], "GDM by NDDG" [OR 5.56 (1.3, 33.3), P=0.018] and "Non-GDM" newborns [OR 6.47 (2.6, 14.8), P=0.0003]. Conclusion: Using the NDDG criteria may increase healthcare costs because while it decreases the number of patients being diagnosed with GDM, it may also increase maternal and neonatal complications without changing maternal healthcare utilization. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of adding the once-weekly DPP-4 inhibitor omarigliptin or the sulfonylurea glimepiride to the treatment regimen of patients with type 2 diabetes (T2DM) and inadequate glycemic control on metformin monotherapy.Methods: Patients with T2DM and HbA1c ≥6.5% to ≤9.0% while on a stable dose of metformin (≥1500 mg/day) were randomized to omarigliptin 25 mg once-weekly (n = 376) or glimepiride up to 6 mg once daily (n = 375) for 54 weeks. The primary hypothesis was that omarigliptin is non-inferior to glimepiride in reducing HbA1c at week 54.Results: The mean baseline HbA1c was 7.5% in the omarigliptin group and 7.4% in the glimepiride group. After 54 weeks, the least squares (LS) mean change from baseline in HbA1c was -0.30% in the omarigliptin group and -0.48% in the glimepiride group, with a between-group difference (95% CI) of 0.18% (0.06, 0.30), which met the pre-specified criterion for declaring non-inferiority. The incidence of symptomatic hypoglycemia was 5.3% in the omarigliptin group and 26.7% in the glimepiride group. With the exception of hypoglycemia, the incidences of adverse events and discontinuations were similar between treatment groups. Relative to baseline, omarigliptin was associated with a mean weight loss (-0.4 kg) and glimepiride a mean weight gain (+1.5 kg).Conclusions: After 54 weeks, as add-on therapy to metformin, once-weekly omarigliptin was generally well tolerated and non-inferior to glimepiride in improving glycemic control, with a lower incidence of hypoglycemia and with weight loss vs weight gain. [ABSTRACT FROM AUTHOR]

The author talks about a study focusing on the role evolution of influenza A(H7N9) virus. Topics discussed include the role of genetic and antigenic mutations in virus evolution; the role of poultry in spreading the virus in China; and the mass immunization of poultry in China. Also mentioned are the virus mutations near surface hemagglutinin (HA).

Objective: Our hypothesis was that newborns of obese mothers would be more likely to be classified as small for gestational age (SGA) by their customized growth curves than by the standard growth curves when compared to newborns of normal-weight mothers.Methods: This is a retrospective cohort of primiparous patients delivering between 1 July 2008 and 30 June 2012. Normal-weight was defined as BMI ≤25 kg/m(2) and obese as BMI ≥ 30 kg/m(2). Infant birth-weight was characterized as SGA or non-SGA from the Lubchenco curve, the Fenton Preterm Growth Chart, and the customized growth curve.Results: Infants were more likely to be classified as SGA on the customized curve compared with Lubchenco curve. Odds ratio was 2.8 (CI: 1.7-4.4; p = 0.001) for obese women and was 2.9 (CI: 1.7-5.1; p < 0.001) for normal-weight women. Infants were also more likely to be classified as SGA based on the customized curve compared with the Fenton Preterm Growth Curve. The odds ratio was 2.3 (CI: 1.4-3.8; p = 0.001) for obese women and was 1.5 (CI: 1.01-2.33; p = 0.04) for normal-weight women.Conclusions: Population-based curves may mask SGA in obese women. Our study demonstrates that customized growth curves identify more SGA than population-based growth curves in obese and normal-weight women. [ABSTRACT FROM AUTHOR]

We assess the impact of social and monetary contextual information on liking ratings of art. A group of art-naive university students (N = 187) was asked to rate a set of 90 paintings for liking, using a 7-point Likert-type scale. Before painting presentation, participants were primed either with information that a certain social group (fellow students, art museum curators/art experts, or low-education/income youth) had rated the painting positively or negatively (social prime, Study 1) or with a fictitious sales price of the artwork (monetary prime, Study 2). These conditions were compared against a control condition in which paintings were viewed without priming information. Results showed a significant effect of both priming types. Paintings with high monetary primes or with high ratings by peers and art experts led to higher participant liking ratings. In contrast, paintings with a low rating by the low-education/income social group led to higher liking ratings by participants. Social priming was also modulated by interest in art and by the level of identification with the social groups. These results provide empirical support for the social "distinction" behavior theory, according to which individuals use their evaluation and engagement with art in order to show allegiance to, or distance themselves from, desirable/undesirable social others, and mark an important area for future research into the analysis of consumer decisions or art preference. [ABSTRACT FROM AUTHOR]

With next-generation sequencing technologies, it is now feasible to efficiently sequence patient-derived virus populations at a depth of coverage sufficient to detect rare variants. However, each sequencing platform has characteristic error profiles, and sample collection, target amplification, and library preparation are additional processes whereby errors are introduced and propagated. Many studies account for these errors by using ad hoc quality thresholds and/or previously published statistical algorithms. Despite common usage, the majority of these approaches have not been validated under conditions that characterize many studies of intrahost diversity. Here, we use defined populations of influenza virus to mimic the diversity and titer typically found in patient-derived samples. We identified single-nucleotide variants using two commonly employed variant callers, Deep- SNV and LoFreq. We found that the accuracy of these variant callers was lower than expected and exquisitely sensitive to the input titer. Small reductions in specificity had a significant impact on the number of minority variants identified and subsequent measures of diversity. We were able to increase the specificity of DeepSNV to>99.95% by applying an empirically validated set of quality thresholds. When applied to a set of influenza virus samples from a household-based cohort study, these changes resulted in a 10-fold reduction in measurements of viral diversity. We have made our sequence data and analysis code available so that others may improve on our work and use our data set to benchmark their own bioinformatics pipelines. Our work demonstrates that inadequate quality control and validation can lead to significant overestimation of intrahost diversity. [ABSTRACT FROM AUTHOR]

While engagement seems to have promising prospects for predicting organizational behavior in domestic organizations, few scholars have included this in cross-cultural management research. We use survey results from 640 self-initiated expatriate academics in Greater China to study the relation between work engagement and intercultural adjustment. We focus on expatriates in Greater China because in terms of economy, this is a fast-growing area and because, with regard to language and culture, this region deviates substantially from the Western countries that most expatriates there come from. This is not least in relation to age perceptions. Contrary to the dominating theoretical position, we found that the different dimensions of work engagement, namely, vigor, dedication, and absorption, have different effects on intercultural adjustment. Moreover, we found that the effect of job dedication on reducing time to proficiency was stronger for older expatriates. [ABSTRACT FROM AUTHOR]

Lethal mutagenesis is a broad-spectrum antiviral strategy that exploits the high mutation rate and low mutational tolerance of many RNA viruses. This approach uses mutagenic drugs to increase viral mutation rates and burden viral populations with mutations that reduce the number of infectious progeny. We investigated the effectiveness of lethal mutagenesis as a strategy against influenza virus using three nucleoside analogs, ribavirin, 5-azacytidine, and 5-fluorouracil. All three drugs were active against a panel of seasonal H3N2 and laboratory-adapted H1N1 strains. We found that each drug increased the frequency of mutations in influenza virus populations and decreased the virus' specific infectivity, indicating a mutagenic mode of action. We were able to drive viral populations to extinction by passaging influenza virus in the presence of each drug, indicating that complete lethal mutagenesis of influenza virus populations can be achieved when a sufficient mutational burden is applied. Population- wide resistance to these mutagenic agents did not arise after serial passage of influenza virus populations in sublethal concentrations of drug. Sequencing of these drug-passaged viral populations revealed genome-wide accumulation of mutations at low frequency. The replicative capacity of drug-passaged populations was reduced at higher multiplicities of infection, suggesting the presence of defective interfering particles and a possible barrier to the evolution of resistance. Together, our data suggest that lethal mutagenesis may be a particularly effective therapeutic approach with a high genetic barrier to resistance for influenza virus. [ABSTRACT FROM AUTHOR]

Two open-label, parallel-group studies evaluated the influence of renal and hepatic insufficiency on the pharmacokinetics of a single-dose anacetrapib 100mg. Eligible participants included adult men and women with moderate hepatic impairment (assessed by Child-Pugh criteria) or severe renal impairment (CrCl<30 mL/min/1.73m²). In both studies, patientswerematched (race, age, sex, BMI) with healthy control subjects. Twenty-four subjects were randomized in each study (12 with eithermoderate hepatic or severe renal impairment and 12 matched healthy controls). In the hepatic insufficiency study, the geometric mean ratio(GMR; mean value for the group with moderate hepatic insufficiency/mean value for the healthy controls) and 90% CIs for the area under the concentration-time curve from time zero to infinity (AUC0-∞) and the maximum concentration of drug in plasma (Cmax) were 1.16 (0.84, 1.60) and 1.02 (0.71, 1.49), respectively. In the renal insufficiency study, the GMRs (mean value for the group with severe renal insufficiency/mean value for the healthy controls) and 90% CIs for AUC0-∞ and Cmax were 1.14 (0.80, 1.63) and 1.31 (0.93, 1.83), respectively. Anacetrapibwas generally well tolerated and there was no clinically meaningful effect of moderate hepatic or severe renal insufficiency on the pharmacokinetics of anacetrapib. [ABSTRACT FROM AUTHOR]

Anacetrapib is a cholesteryl ester transfer protein inhibitor in Phase III development. This double-blind, double-dummy, randomized, placebo- and active-comparator-controlled, 4-period, balanced crossover study evaluated the effects of anacetrapib (100 mg and 800 mg) on QTcF interval in healthy subjects. QTcF measurements were made up to 24 h following administration of single doses of anacetrapib 100 or 800 mg, moxifloxacin 400 mg, or placebo in the fed state. The primary hypothesis was supported if the 90% CI for the least squares (LS) mean differences between anacetrapib 800 mg and placebo in QTcF interval change from baseline were entirely <10 msec at every post-dose time point (1, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 h). The upper bounds of the 90% CIs for LS mean differences from placebo in changes from baseline in QTcF intervals for anacetrapib 100 and 800 mg were <5 msec at every time point. In conclusion, single doses of anacetrapib 100 and 800 mg do not prolong the QTcF interval to a clinically meaningful degree relative to placebo and are generally well tolerated in healthy subjects. [ABSTRACT FROM AUTHOR]

Despite the apparent increasing internationalization of the academic world, research on expatriate academics has remained negligible compared to the literature on business expatriates, which has increased rapidly in recent years. This is regrettable, since it is not obvious to what extent research findings regarding business expatriates also are applicable to expatriate academics. To examine cognitive and affective reasons to expatriate and work adjustment, a questionnaire was directed electronically towards expatriate academics from 60 countries employed in 35 universities in 5 northern European countries. Results indicated that one of the affective reasons to expatriate, refugee reasons (life change/escape), has a clear negative influence on both job adjustment and time to proficiency. However, none of the other studied reasons for expatriate academics to go abroad had any association with their subsequent adjustment to work. Hence, explorer reasons (adventure/travel), architect reasons (careers) or mercenary reasons (financial incentives) do not seem to have any effect on how well expatriate academics adjust to their work abroad. Implications of these findings are discussed in detail. [ABSTRACT FROM AUTHOR]

Aims: The objective of this study was to examine the impact of one trial (the HYP1TAT trial) on management of gestational hypertension. Study design: This is a retrospective cohort study of 5077 patients delivered at our institution from 7/1/2008 to 6/15/2011. "Pre-HYPITAT" was defined as 7/1/2008-9/30/2009 and "Post-HYPITAT" as 10/1/2009-6/15/2011. The primary outcome is the rate of delivery intervention for gestational hypertension. Secondary maternal and neonatal outcomes were analyzed in patients with gestational hypertension only. Statistical analyses included the χ²-test. Fisher's exact test, and the two-sample t-test. Results: The rate of delivery intervention Pre-HYPITAT was 1.9%, compared to4% Post-HYPITAT (P<0.001). There was no significant change in secondary outcomes. Conclusion: There was a statistically significant increase in delivery intervention for gestational hypertension at our institution after the publication of the HYPITAT trial. There was no significant change in immediate maternal or neonatal outcomes for patients with gestational hypertension. [ABSTRACT FROM AUTHOR]

RNA viruses face dynamic environments and are masters at adaptation. During their short 'lifespans', they must surmount multiple physical, anatomical and immunological challenges. Central to their adaptative capacity is the enormous genetic diversity that characterizes RNA virus populations. Although genetic diversity increases the rate of adaptive evolution, low replication fidelity can present a risk because excess mutations can lead to population extinction. In this Review, we discuss the strategies used by RNA viruses to deal with the increased mutational load and consider how this mutational robustness might influence viral evolution and pathogenesis. [ABSTRACT FROM AUTHOR]

Joint work among academic staff is important for solving the ever-increasing number of complex tasks that are becoming part of everyday activities in higher education. At the same time, diversification and internationalisation may challenge collaboration processes and communication demands. Speaking a shared language consistently could be a way of overcoming problems. Hence, this study focuses on the effect of shared language among academic staff on the relation between academic staff involvement in work processes and openness to diversity. This study draws on data from 489 Danish academic staff members in science departments of three universities. Results show positive associations between academic staff involvement and all openness-to-diversity variables (openness to informational, linguistic, value and visible diversity). Shared language had a positive effect on openness to surface level types of diversity (linguistic and visible) but no effect on openness to deep-level types of diversity (informational and value). [ABSTRACT FROM AUTHOR]

Many human immunodeficiency virus (HIV) infected individuals suffer from persistent immune activation. Chronic inflammation and immune dysregulation have been associated with an increased risk of age-related diseases even among patients on highly active antiretroviral therapy. The factors leading to immune activation are complex, but have been hypothesized to include persistent viral replication with cellular death as well as microbial translocation across the gastrointestinal tract. Both processes may trigger innate immune responses since many native molecules released from dying cells are similar in structure to pathogen associated molecular patterns. These damage associated molecular patterns include mitochondrial DNA and formylated peptides. We hypothesized that circulating mitochondrial nucleic acid could serve as a biomarker for HIV-associated cell death and drive innate immune activation in infected individuals. We developed a quantitative polymerase chain reaction assay for plasma mitochondrial DNA and validated it on normal blood donors. We then measured mitochondrial DNA levels in acute and chronic HIV infection. While the assay proved to be accurate with a robust dynamic range, we did not find a significant association between HIV disease status and circulating mitochondrial DNA. We did, however, observe a negative correlation between age and plasma mitochondrial DNA levels in individuals with well-controlled HIV. [ABSTRACT FROM AUTHOR]

G-protein coupled receptor (GPCR) GPR109a is a moleculartarget for nicotinic acid and is expressed in adipocytes, spleen,and immune cells. Nicotinic acid has long been used for the treatmentof dyslipidemia due to its capacity to positively affect serum lipidsto a greater extent than other currently marketed drugs. We reporta series of tricyclic pyrazole carboxylic acids that are potent andselective agonists of GPR109a. Compound R,R-19a(MK-1903) was advanced through preclinicalstudies, was well tolerated, and presented no apparent safety concerns.Compound R,R-19awasadvanced into a phase 1 clinical trial and produced a robust decreasein plasma free fatty acids. On the basis of these results, R,R-19awas evaluated in aphase 2 study in humans. Because R,R-19aproduced only a weak effect on serum lipids ascompared with niacin, we conclude that the beneficial effects of niacinare most likely the result of an undefined GPR109a independent pathway. [ABSTRACT FROM AUTHOR]

Background: A good social climate is a precondition for developing a well functioning staff in university departments. However, as universities are becoming increasingly diverse in their staff composition, new problems for the social climate may develop. Organisations where members are open to diversity are known to be better integrated and to perform better. While the relation between a positive social climate and group functioning is well documented, we know much less about antecedents for such a climate. Purpose: The aim of this study is to examine the effect of internal learning and knowledge sharing engagement (sharing informal knowledge of a personal nature and the staff's application of each other's knowledge to task relevant problems) on diversity climate (openness to linguistic, visual, value and informational diversity) among university teachers. Sample: The study used questionnaire responses from 489 teachers in multicultural Danish university departments. Design and methods: To study antecedents for a good diversity climate, statistical analysis including hierarchical multiple regressions was applied. Conclusions: Results showed that group members' engagement in: (1) sharing informal knowledge of a personal nature; and (2) their application of each other's knowledge to task relevant problems had strong positive associations with openness to linguistic, visible, value and informational diversity. We conclude that interaction and knowledge sharing among teachers in multicultural departments is likely to have a favourable effect on the social working climate. [ABSTRACT FROM AUTHOR]

Purpose – The literature on business expatriates has been increasing rapidly, but research on expatriate academics has remained scant, despite the apparent increasing globalisation of the academic world. Therefore, more research is needed on the latter group of expatriates. This paper aims to fill some of the gaps. Design/methodology/approach – A questionnaire was directed electronically towards expatriate academics occupying regular positions in science faculty departments in universities in northern Europe. Findings – Results showed that job clarity was the dominating job factor with strong relationships with all of the five investigated work outcome variables, work adjustment, work performance, work effectiveness, job satisfaction, and time to proficiency. Job conflict and job freedom had an association with some of the work outcome variables but not with all of them. Neither workload nor job novelty had a relationship with any of the work outcome variables of the expatriate academics. Originality/value – The paper shows that the findings are only partly consistent with previous research results concerning business expatriates, suggesting that the work situation for expatriate academics could have both similarities and discrepancies as compared to that of business expatriates. [ABSTRACT FROM AUTHOR]

There is growing evidence that the use and management of language have important implications in international organizations. However, still only few empirical studies have been conducted in this theoretical field. Especially there has been a lack of quantitative insights into how language affects group processes and group performance in multicultural organizations. This paper outlines the results from a questionnaire directed electronically towards members of academic multicultural departments in Denmark. Results showed that consistency in English management communication was the dominating factor with strong relationships with all of the three investigated group cohesiveness variables: group involvement, group conflict and group trust. Communication frequency and English personal communication had an association with some of the group cohesiveness variables but not with all of them. The number of languages spoken did not have a relationship with any of the group cohesiveness variables. Since there are no similar large-scale studies on international language management, the findings may be of considerable theoretical and practical importance. Implications of these findings are discussed in detail. [ABSTRACT FROM PUBLISHER]

Abstract: While most studies on diverse organizations have been directed at business organizations, the academic sector has also become increasingly international and heterogeneous. Few large-scale studies have investigated multicultural academic departments and none of those have dealt with diversity and group processes. Therefore, a survey was directed towards academics in 16 science departments in three large universities in Denmark. Results based on the response from 489 academics showed that cultural diversity, as a deep level heterogeneity, was positively related to performance and satisfaction, whereas gender diversity, as a surface level heterogeneity, was negatively associated with satisfaction. Implications of these findings are discussed in detail. [Copyright &y& Elsevier]

A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy. [ABSTRACT FROM AUTHOR]

The design of vaccines against viral disease has evolved considerably over the past 50 years. Live attenuated viruses (LAVs)—those created by passaging a virus in cultured cells—have proven to be an effective means for preventing many viral diseases, including smallpox, polio, measles, mumps and yellow fever. Even so, empirical attenuation is unreliable in some cases and LAVs pose several safety issues. Although inactivated viruses and subunit vaccines alleviate many of these concerns, they have in general been less efficacious than their LAV counterparts. Advances in molecular virology—creating deleterious gene mutations, altering replication fidelity, deoptimizing codons and exerting control by microRNAs or zinc finger nucleases—are providing new ways of controlling viral replication and virulence and renewing interest in LAV vaccines. Whereas these rationally attenuated viruses may lead to a new generation of safer, more widely applicable LAV vaccines, each approach requires further testing before progression to human testing. [ABSTRACT FROM AUTHOR]

An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. Here, we create a physiologic in vitro model to study the effects of this mutation by using somatic cell gene targeting using the nontumorigenic human breast epithelial cell line, MCF10A. Surprisingly, knock in of E17K into the AKT1 gene had minimal phenotypic consequences and importantly, did not recapitulate the biochemical and growth characteristics seen with somatic cell knock in of PIK3CA hotspot mutations. These results suggest that mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve oncogenic PI3K pathway activation in cancers that contain the AKT1 E17K mutation. [ABSTRACT FROM AUTHOR]

The author discusses his project as a virologist to understand minimally virulent clone evolved to cause tumors in some cats and an AIDS-like immunodeficiency in others. He discusses how his mentor Julie Overbaugh discussed lymphoma-derived feline leukemia virus (FeLV) that had picked up a piece of a cellular gene and made a mutant version of the corresponding protein.

Laropiprant, an antagonist of the PGD2 receptor, DP1, is effective in reducing the flushing symptoms associated with extended-release (ER) niacin and thereby improves the tolerability of niacin therapy for dyslipidemia. Because PGD2 has been reported to inhibit platelet aggregation in vitro, it has been speculated that antagonism of DP1 may enhance platelet reactivity. Three clinical studies evaluated the potential effect of laropiprant, with or without coadministration of ER niacin, on in vivo platelet function in healthy subjects and hypercholesterolemic or diabetic subjects by measuring urinary levels of 11-dehydrothromboxane B2 (11-dTxB2), a marker of in vivo platelet activation. Following 7 days of multiple-dose administration, coadministration of laropiprant with ER niacin did not increase urinary 11-dTxB2 levels compared to ER niacin alone in healthy, hypercholesterolemic, or diabetic subjects. In hypercholesterolemic and diabetic subjects, laropiprant did not increase urinary 11-dTxB2 levels compared to placebo. These results demonstrate that laropiprant does not enhance in vivo platelet reactivity, either alone or in combination with niacin. [ABSTRACT FROM AUTHOR]

Laropiprant, an antagonist of the PGD2 receptor, DP1, is effective in reducing the flushing symptoms associated with extended-release (ER) niacin and thereby improves the tolerability of niacin therapy for dyslipidemia. Because PGD2 has been reported to inhibit platelet aggregation in vitro, it has been speculated that antagonism of DP1 may enhance platelet reactivity. Three clinical studies evaluated the potential effect of laropiprant, with or without coadministration of ER niacin, on in vivo platelet function in healthy subjects and hypercholesterolemic or diabetic subjects by measuring urinary levels of 11-dehydrothromboxane B2 (11-dTxB2), a marker of in vivo platelet activation. Following 7 days of multiple-dose administration, coadministration of laropiprant with ER niacin did not increase urinary 11-dTxB2 levels compared to ER niacin alone in healthy, hypercholesterolemic, or diabetic subjects. In hypercholesterolemic and diabetic subjects, laropiprant did not increase urinary 11-dTxB2 levels compared to placebo. These results demonstrate that laropiprant does not enhance in vivo platelet reactivity, either alone or in combination with niacin. [ABSTRACT FROM AUTHOR]

ABSTRACTObjective:The objective of this study was to compare pharmacokinetic parameters of niacin extended-release tablets (NER uncoated)and niacin extended-release caplet formation (NER coated)†. Niaspan is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA†Niaspan CF is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USAResearch design and methods: Twenty-five healthy male and female subjects were enrolled in a four-period, open-label, randomized, crossover study. Both NER uncoated and NER coated were given as 1 × 1000 mg or 2 × 500 mg tablets. Similarity of NER coated 1 × 1000 mg and NER uncoated 2 × 500 mg was declared if 90 confidence intervals for the geometric mean ratio (GMR) for nicotinuric acid (NUA) Cmaxfell within the pre-specified bounds of [0.7, 1.43].Results:The GMRs for NUA Cmaxdemonstrated similarity in the pharmacokinetics of NER uncoated 2 × 500 mg, NER coated 1 × 1000 mg, and NER coated 2 × 500 mg. Although less stringent comparability bounds were prespecified for the primary pharmacokinetic endpoint (i.e., Cmaxof plasma NUA), inspection of the primary comparison of interest indicated that a hypothesis with more stringent bioequivalence bounds of [0.8, 1.25] would have been satisfied. The NUA Cmaxfor NER uncoated 1 × 1000 mg was approximately 40 higher than that seen for the other three treatments. In contrast, total urinary excretion of niacin and its metabolites, an approximate measure of bioavailability, was similar for all four treatments.Conclusion:The pharmacokinetic profile of the original NER uncoated formulation dosed as 2 × 500 mg was similar to the new film-coated formulation, NER coated, dosed as 1 × 1000 mg. [ABSTRACT FROM AUTHOR]

In a globalized business environment, interaction across linguistic boundaries is becoming a normal part of everyday life. In these encounters language differences may affect the formation of social identities among organization members. While studies based on Social Identity Theory perceive the link between identity and language to be linear, this article takes a different approach. By drawing on anthropological theories on ethnic identity it is argued that the relation between language and social identity is negotiated in interaction. In the empirical analysis the article focuses on the encounter between expatriates and local employees of a Danish subsidiary in England. The findings show that identity making may be actualized by competition for resources and recognition. This can be done by investing certain objects such as the symbolic application of language with certain identifications. It is finally argued that the processes by which identifications develop can cause both polarization and accommodation in the relation between groups and individuals. [ABSTRACT FROM AUTHOR]

AAA+ adenosine triphosphatases (ATPases) are molecular machines that perform a wide variety of cellular functions. For instance, they can act in vesicle transport, organelle assembly, membrane dynamics and protein unfolding. In most cases, the ATPase domains of these proteins assemble into active ring-shaped hexamers. As AAA+ proteins have a common structure, a central issue is determining how they use conserved mechanistic principles to accomplish specific biological actions. Here, we review the features and motifs that partially define AAA+ domains, describe the cellular activities mediated by selected AAA+ proteins and discuss the recent work, suggesting that various AAA+ machines with very different activities employ a common core mechanism. The importance of this mechanism to human health is demonstrated by the number of genetic diseases caused by mutant AAA+ proteins. [ABSTRACT FROM AUTHOR]

This article presents the case of a 64-year-old man with a history of coronary artery disease and peripheral vascular disease who was admitted to the hospital with a several-month history of fevers, chills and fatigue. The case is presented in stages with the comments from an expert clinician. The patient's symptoms began after he had a stent put in his left anterior descending coronary artery ten months before admission. Treatment at this time is discussed with the history that the patient had to have the stent removed and a new one inserted. Following several tests it was found that the patient had a periprosthetic enteric fistula between the terminal duodenum and the promixal right limb of the aortobifemoral bypass graft.

Although expression of the RAG1 and RAG2 genes is essential for lymphocyte development, the mechanisms responsible for the lymphoid- and developmental stage-specific regulation of these genes are poorly understood. We have identified a novel, evolutionarily conserved transcriptional enhancer in the RAG locus, called Erag, which was essential for the expression of a chromosomal reporter gene driven by either RAG promoter. Targeted deletion of Erag in the mouse germline results in a partial block in B cell development associated with deficient V(D)J recombination, whereas T cell development appears unaffected. We found that E2A transcription factors bind to Erag in vivo and can transactivate Erag-dependent reporter constructs in cotransfected cell lines. These findings lead us to conclude that RAG transcription is regulated by distinct elements in developing B and T cells and that Erag is required for optimal levels of RAG expression in early B cell precursors but not in T cells. [Copyright &y& Elsevier]

Aims of the study. The aim of this study was to better understand the ways in which conditions of work, including staffing, affect how nurses in long-term care (LTC) facilities do their jobs and the quality of care they provide. Background. The research reported here was performed in the context of public policy debates about the relationship between staffing levels and quality in LTC. Methods. In 1995 and 1996, interviews and participant observation were used to examine how 18 licensed nurses employed in two LTC facilities in the midwestern United States experience their day-to-day work. Results. Time was an extremely salient work condition for the nurses interviewed. Under conditions of too little time and many interruptions, nurses compensated by developing strategies to keep up or catch up. These strategies included minimizing the time spent doing required tasks, creating new time and redefining work responsibilities. Although these strategies allowed nurses to complete the tasks for which they were accountable, there were adverse consequences for nurses and residents. Nurses realized that time demands often made it impossible to provide care of high quality. They expressed their ideas about quality care as the notion of 'should do' work. In effect, time pressures forced them to forego the 'should do' work to complete the 'must do' work. Conclusion. Increased staffing could improve the quality of care in LTC facilities. [ABSTRACT FROM AUTHOR]

Focuses on the management of time and work on the nursing long-term care facilities. Observation of the professional practice activities; Determination of the organizational patterns on the fieldwork; Indication of quality care on the patients.

This JAMA Patient Page explains what virus variants are and describes several recent variants of the SARS-CoV-2 virus and the public health concerns relating to these variants. [ABSTRACT FROM AUTHOR]

Background: JNJ-78306358 is a bispecific antibody that redirects T cells to kill human leukocyte antigen-G (HLA-G)-expressing tumor cells. This dose escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of JNJ-78306358 in patients with advanced solid tumors. Methods: Adult patients with metastatic/unresectable solid tumors with high prevalence of HLA-G expression were enrolled. Dose escalation was initiated with once-weekly subcutaneous administration with step-up dosing to mitigate cytokine release syndrome (CRS). Results: Overall, 39 heavily pretreated patients (colorectal cancer: n = 23, ovarian cancer: n = 10, and renal cell carcinoma: n = 6) were dosed in 7 cohorts. Most patients (94.9%) experienced ≥ 1 treatment-emergent adverse events (TEAEs); 87.2% had ≥ 1 related TEAEs. About half of the patients (48.7%) experienced CRS, which were grade 1/2. Nine patients (23.1%) received tocilizumab for CRS. No grade 3 CRS was observed. Dose-limiting toxicities (DLTs) of increased transaminases, pneumonitis and recurrent CRS requiring a dose reduction were reported in 4 patients, coinciding with CRS. No treatment-related deaths reported. No objective responses were noted, but 2 patients had stable disease > 40 weeks. JNJ-78306358 stimulated peripheral T cell activation and cytokine release. Anti-drug antibodies were observed in 45% of evaluable patients with impact on exposure. Approximately half of archival tumor samples (48%) had expression of HLA-G by immunohistochemistry. Conclusion: JNJ-78306358 showed pharmacodynamic effects with induction of cytokines and T cell activation. JNJ-78306358 was associated with CRS-related toxicities including increased transaminases and pneumonitis which limited its dose escalation to potentially efficacious levels. Trial registration number ClinicalTrials.gov (No. NCT04991740). [ABSTRACT FROM AUTHOR]

Objective The primary objective was to determine if vaginal progesterone following cerclage for cervical length <10 mm or cervical dilation in patients without a history of spontaneous preterm birth (sPTB) decreased the risk of preterm birth at <34 weeks' gestation compared with cerclage alone. Secondary objectives were to determine if vaginal progesterone following cerclage (1) decreased the risk of preterm birth at <24, <28, and <37 weeks' gestation and (2) increased the latency period from cerclage placement to delivery compared with treatment with cerclage alone. Study Design Multicenter retrospective cohort study from 2015 to 2020 of singleton pregnancies, without prior sPTB, who had cerclage placement <24 weeks' gestation for cervical length <10 mm or cervical dilation. Exposure defined as cerclage plus vaginal progesterone postoperatively (dual therapy) and unexposed as cerclage alone (monotherapy), based on surgeon preference. Results We included 122 patients, 78 (64%) treated with dual therapy and 44 (36%) treated with monotherapy. In the crude analysis, dual therapy was associated with a lower risk of delivery at <28 weeks' gestation (13%) compared with monotherapy (34%; crude risk ratio: 0.38 [95% confidence interval (CI): 0.19–0.75]). When adjusted for preoperative vaginal progesterone, results were attenuated (adjusted risk ratio: 0.45 [95% CI: 0.20–1.01]). In both the crude and adjusted analyses, the risk of sPTB was not statistically different at <24, <34 or <37 weeks' gestation. Dual therapy was associated with a greater pregnancy latency from cerclage to delivery (16.3 vs. 14.4 weeks; p = 0.04), and greater gestational age at delivery (37.3 vs. 35.8 weeks' gestation; p = 0.02) compared with monotherapy. Conclusion While not statistically significant, the risk of sPTB was lower at all gestational ages studied in patients treated with dual therapy compared with monotherapy. Dual therapy was associated with longer pregnancy latency and greater gestational age at delivery compared with monotherapy. Key Points Dual therapy did not decrease preterm birth risk compared with monotherapy. Dual therapy prolonged pregnancy compared with monotherapy. Dual therapy can be considered but further studies are needed. [ABSTRACT FROM AUTHOR]

The human leukocyte antigen (HLA) system plays a pivotal role in the immune response to viral infections, mediating the presentation of viral peptides to T cells and influencing both the strength and specificity of the host immune response. Variations in HLA genotypes across individuals lead to differences in susceptibility to viral infection and severity of illness. This study uses observations from the early phase of the COVID-19 pandemic to explore how specific HLA class I molecules affect clinical responses to SARS-CoV-2 infection. By analyzing paired high-resolution HLA types and viral genomic sequences from 60 patients, we assess the relationship between predicted HLA class I peptide binding repertoires and infection severity as measured by the sequential organ failure assessment score. This approach leverages functional convergence across HLA-C alleles to identify relationships that may otherwise be inaccessible due to allelic diversity and limitations in sample size. Surprisingly, our findings show that severely symptomatic infection in this cohort is associated with disproportionately abundant binding of SARS-CoV-2 structural and non-structural protein epitopes by patient HLA-C molecules. In addition, the extent of overlap between a given patient's predicted HLA-C and HLA-A peptide binding repertoires correlates with worse prognoses in this cohort. The findings highlight immunologic mechanisms linking HLA-C molecules with the human response to viral pathogens that warrant further investigation. [ABSTRACT FROM AUTHOR]

The article explores the theoretical and experimental concepts in the evolution of virus. Topics discussed include the strengths and weaknesses of virulence theory, definition of virulence, rate of viral transmission, mortality due to infection, recovery rate from infection, susceptible host density, modeling of virulence evolution, and intrinsic limits on pathogen replication and transmission.