Shiga toxin-producing Escherichia coli isolated from hunted wild boar (Sus scrofa) in Switzerland.

INTRODUCTION: Shiga toxin-producing Escherichia (E.) coli (STEC) are zoonotic foodborne pathogens of significant public health importance. While ruminants are considered the main reservoir, wild animals are increasingly acknowledged as carriers and potential reservoirs of STEC. The aim of this study was to determine the occurrence of STEC in a total of 59 faecal samples of hunted wild boars (Sus scrofa) from two different regions in Switzerland (canton Thurgau in northern Switzerland and canton Ticino in southern Switzerland), and to characterise the isolates using a whole genome sequencing approach. After an enrichment step, Shiga-toxin encoding genes (stx) were detected by real-time PCR in 41 % (95 % confidence interval (95 %CI) 0,29 - 0,53) of the samples, and STEC were subsequently recovered from 22 % (95 %CI 0,13 - 0,34) of the same samples. Seven different serotypes and six different sequence types (STs) were found, with O146:H28 ST738 (n = 4) and O100:H20 ST2514 (n = 4) predominating. Subtyping of stx identified isolates with stx1c/stx2b (n = 1), stx2a (n = 1), stx2b (n = 6), and stx2e (n = 6). No isolate contained the eae gene, but all harboured additional virulence genes, most commonly astA (n = 10), hlyE (n = 9), and hra (n = 9). STEC O11:H5, O21:H21, and O146:H28 harboured virulence factors associated with extra-intestinal pathogenic E. coli (ExPEC), and STEC O100:H20 and O155:H26 possessed sta1 and/or stb and were STEC/enterotoxigenic E. coli (ETEC) hybrid pathotypes. Our results show that wild boars are carriers of STEC which may be distributed in the environment, possibly leading to the contamination of agricultural crops and water sources. The serogroups included STEC O146 which belongs to the most common non-O157 serogroups associated with human illness in Europe, with implications for public health. Since Stx2e-producing STEC have frequently been reported in swine and pork, STEC O100:H20 harbouring stx2e in faeces of wild boars may be relevant to free-range systems of pig farming because of the potential risk of transmission events at the wildlife-livestock interface.

INTRODUCTION: Les Escherichia (E.) coli producteurs de shiga-toxine (STEC) sont des agents pathogènes zoonotiques d'origine alimentaire qui revêtent une grande importance pour la santé publique. Alors que les ruminants sont considérés comme le principal réservoir, les animaux sauvages sont de plus en plus souvent reconnus comme porteurs et réservoirs potentiels de STEC. L'objectif de cette étude était de déterminer la présence de STEC dans un total de 59 échantillons fécaux de sangliers (Sus scrofa) chassés provenant de deux régions différentes de Suisse (canton de Thurgovie dans le nord de la Suisse et canton du Tessin dans le sud de la Suisse) et de caractériser les isolats en utilisant une approche de séquençage du génome entier. Après une étape d'enrichissement, les gènes codant pour la Shiga-toxine (stx) ont été détectés par PCR en temps réel dans 41% (intervalle de confiance à 95% (95%CI) 0,29 - 0,53) des échantillons, et les STEC ont ensuite été récupérés dans 22% (95%CI 0,13 - 0,34) des mêmes échantillons. Sept sérotypes différents et six types de séquence (ST) différents ont été trouvés, avec une prédominance de O146:H28 ST738 (n = 4) et O100:H20 ST2514 (n = 4). Le sous-typage des stx a permis d'identifier des isolats avec stx1c/stx2b (n = 1), stx2a (n = 1), stx2b (n = 6) et stx2e (n = 6). Aucun isolat ne contenait le gène eae, mais tous hébergeaient d'autres gènes de virulence, le plus souvent astA (n = 10), hlyE (n = 9) et hra (n = 9). Les STEC O11:H5, O21:H21 et O146:H28 présentaient des facteurs de virulence associés à des E. coli pathogènes extra-intestinaux (ExPEC), et les STEC O100:H20 et O155:H26 possédaient sta1 et/ou stb et étaient des pathotypes hybrides STEC/E. coli entérotoxinogène (ETEC).

The variable source of the plasma sheet during a geomagnetic storm.

Both solar wind and ionospheric sources contribute to the magnetotail plasma sheet, but how their contribution changes during a geomagnetic storm is an open question. The source is critical because the plasma sheet properties control the enhancement and decay rate of the ring current, the main cause of the geomagnetic field perturbations that define a geomagnetic storm. Here we use the solar wind composition to track the source and show that the plasma sheet source changes from predominantly solar wind to predominantly ionospheric as a storm develops. Additionally, we find that the ionospheric plasma during the storm main phase is initially dominated by singly ionized hydrogen (H+), likely from the polar wind, a low energy outflow from the polar cap, and then transitions to the accelerated outflow from the dayside and nightside auroral regions, identified by singly ionized oxygen (O+). These results reveal how the access to the magnetotail of the different sources can change quickly, impacting the storm development.

Fiber reinforced hydrated networks recapitulate the poroelastic mechanics of articular cartilage.

The role of poroelasticity on the functional performance of articular cartilage has been established in the scientific literature since the 1960s. Despite the extensive knowledge on this topic there remain few attempts to design for poroelasticity and to our knowledge no demonstration of an engineered poroelastic material that approaches the physiological performance. In this paper, we report on the development of an engineered material that begins to approach physiological poroelasticity. We quantify poroelasticity using the fluid load fraction, apply mixture theory to model the material system, and determine cytocompatibility using primary human mesenchymal stem cells. The design approach is based on a fiber reinforced hydrated network and uses routine fabrication methods (electrohydrodynamic deposition) and materials (poly[ɛ-caprolactone] and gelatin) to develop the engineered poroelastic material. This composite material achieved a mean peak fluid load fraction of 68%, displayed consistency with mixture theory, and demonstrated cytocompatibility. This work creates a foundation for designing poroelastic cartilage implants and developing scaffold systems to study chondrocyte mechanobiology and tissue engineering. STATEMENT OF SIGNIFICANCE: Poroelasticity drives the functional mechanics of articular cartilage (load bearing and lubrication). In this work we develop the design rationale and approach to produce a poroelastic material, known as a fiber reinforced hydrated network (FiHy™), that begins to approach the native performance of articular cartilage. This is the first engineered material system capable of exceeding isotropic linear poroelastic theory. The framework developed here enables fundamental studies of poroelasticity and the development of translational materials for cartilage repair.

Comparative evaluation of Luminex based assays for detection of SARS-CoV-2 antibodies in a transplantation laboratory.

BACKGROUND: Detection of SARS-CoV-2 antibodies is essential in establishing the parameters of an individual's immune response to COVID-19, from both natural infection and vaccination. Despite this, there is currently limited clinical guidance or recommendations for serological methods for their measurement. Here, we evaluate and compare four Luminex-based assays for the multiplex detection of IgG SARS-CoV-2 antibodies. METHODS: The four assays tested were Magnetic Luminex Assay, MULTICOV-AB Assay, Luminex xMAP SARS-CoV-2 Multi-Antigen IgG Assay and LABScreen COVID Plus Assay. Each assay's ability to detect antibodies to SARS-CoV-2 Spike (S), Nucleocapsid (N) and Spike-Receptor Binding Domain (RBD) was evaluated using 50 test samples (25 positive, 25 negative), previously tested by a widely used ELISA technique. RESULTS: The MULTICOV-AB Assay had the highest clinical performance detecting antibodies to S trimer and RBD in 100% (n = 25) of known positive samples. Both the Magnetic Luminex Assay and LABScreen COVID Plus Assay showed significant diagnostic accuracy with sensitivities of 90% and 88% respectively. The Luminex xMAP SARS-CoV-2 Multi-Antigen IgG Assay demonstrated limited detection of antibodies to the S antigen resulting in a sensitivity of 68%. CONCLUSION: Luminex-based assays provide a suitable serological method for multiplex detection of SARS-CoV-2 specific antibodies, with each assay able to detect antibodies to a minimum of 3 different SARS-CoV-2 antigens. Assay comparison identified there is moderate performance variability between manufacturers and further inter-assay variation of antibodies detected to different SARS-CoV-2 antigens.

Entrenamiento procedimental básico (EPROBA) en suturas para estudiantes de medicina durante pandemia por SARS-CoV-2 (COVID-19) / Suturing basic procedural skills training for medical students during COVID-19 pandemic

BACKGROUND: The adoption of sanitary measures due to the SARS-CoV-2 pandemic hampered teaching and learning methods in medicine. AIM: To communicate the results of a wound suture training workshop, based on the Basic Procedural Skills Training methodology and adapted to the pandemic context. MATERIAL AND METHODS: One hundred fourteen students were randomized in small groups due to sanitary measures and trained with a modification of the Basic Procedural Skills Training methodology. An informed consent was obtained from every student. The suturing skills were evaluated before and after the intervention with "The Objective Structured Assessment Of Technical Skills" (OSATS) instrument. The perception of the workshop and the implementation of the COVID-19 prevention measures were also evaluated. RESULTS: The students showed a statistically significant improvement after the intervention. In the OSATS verification list, the average score increased from 4.5 to 8.6 (p < 0.01). In the OSATS global scale, the average score increased from 13.0 to 25.3 (p < 0.01). The perception of the workshop and the prevention measures were well evaluated. CONCLUSIONS: Despite all the limitations of the pandemic context, we achieved a significant improvement after the intervention and a very good perception by the students.

Intrinsic cell rheology drives junction maturation.

A fundamental property of higher eukaryotes that underpins their evolutionary success is stable cell-cell cohesion. Yet, how intrinsic cell rheology and stiffness contributes to junction stabilization and maturation is poorly understood. We demonstrate that localized modulation of cell rheology governs the transition of a slack, undulated cell-cell contact (weak adhesion) to a mature, straight junction (optimal adhesion). Cell pairs confined on different geometries have heterogeneous elasticity maps and control their own intrinsic rheology co-ordinately. More compliant cell pairs grown on circles have slack contacts, while stiffer triangular cell pairs favour straight junctions with flanking contractile thin bundles. Counter-intuitively, straighter cell-cell contacts have reduced receptor density and less dynamic junctional actin, suggesting an unusual adaptive mechano-response to stabilize cell-cell adhesion. Our modelling informs that slack junctions arise from failure of circular cell pairs to increase their own intrinsic stiffness and resist the pressures from the neighbouring cell. The inability to form a straight junction can be reversed by increasing mechanical stress artificially on stiffer substrates. Our data inform on the minimal intrinsic rheology to generate a mature junction and provide a springboard towards understanding elements governing tissue-level mechanics.

Polymer formulated self-amplifying RNA vaccine is partially protective against influenza virus infection in ferrets.

COVID-19 has demonstrated the power of RNA vaccines as part of a pandemic response toolkit. Another virus with pandemic potential is influenza. Further development of RNA vaccines in advance of a future influenza pandemic will save time and lives. As RNA vaccines require formulation to enter cells and induce antigen expression, the aim of this study was to investigate the impact of a recently developed bioreducible cationic polymer, pABOL for the delivery of a self-amplifying RNA (saRNA) vaccine for seasonal influenza virus in mice and ferrets. Mice and ferrets were immunized with pABOL formulated saRNA vaccines expressing either haemagglutinin (HA) from H1N1 or H3N2 influenza virus in a prime boost regime. Antibody responses, both binding and functional were measured in serum after immunization. Animals were then challenged with a matched influenza virus either directly by intranasal inoculation or in a contact transmission model. While highly immunogenic in mice, pABOL-formulated saRNA led to variable responses in ferrets. Animals that responded to the vaccine with higher levels of influenza virus-specific neutralizing antibodies were more protected against influenza virus infection. pABOL-formulated saRNA is immunogenic in ferrets, but further optimization of RNA vaccine formulation and constructs is required to increase the quality and quantity of the antibody response to the vaccine.

Morbidities among older workers and work exit: the HEAF cohort.

BACKGROUND: Governments need people to work to older ages, but the prevalence of chronic disease and comorbidity increases with age and impacts work ability. AIMS: To investigate the effects of objective health diagnoses on exit from paid work amongst older workers. METHODS: Health and Employment After Fifty (HEAF) is a population cohort of adults aged 50-64 years recruited from English GP practices which contribute to the Clinical Practice Research Datalink (CPRD). Participants have completed questionnaires about health and work at baseline and annually for 2 years: their responses were linked with their objective health diagnoses from the CPRD and data analysed using Cox regression. RESULTS: Of 4888 HEAF participants ever in paid work, 580 (25%) men and 642 (25%) women exited employment, 277 of them mainly or partly for a health reason (health-related job loss (HRJL)). Amongst HEAF participants who remained in work (n = 3666) or who exited work but not for health reasons (n = 945), there was a similar prevalence of background health conditions. In men and women, HRJL was associated with inflammatory arthritis, sleep disorders, common mental health conditions and musculoskeletal pain. There were however gender differences: widespread pain and lower limb osteoarthritis were associated with HRJL in women but hypertension and cardiovascular disease in men. CONCLUSIONS: Improved diagnosis and management of common conditions might be expected to increase working lives. Workplace well-being interventions targeting obesity and increasing mobility might contribute to extended working lives. Employers of predominantly female, as compared with male workforces may need different strategies to retain older workers.

Quantifying the reduction of respiratory motion by mechanical ventilation with MRI for radiotherapy.

BACKGROUND: Due to respiratory motion, accurate radiotherapy delivery to thoracic and abdominal tumors is challenging. We aimed to quantify the ability of mechanical ventilation to reduce respiratory motion, by measuring diaphragm motion magnitudes in the same volunteers during free breathing (FB), mechanically regularized breathing (RB) at 22 breaths per minute (brpm), variation in mean diaphragm position across multiple deep inspiration breath-holds (DIBH) and diaphragm drift during single prolonged breath-holds (PBH) in two MRI sessions. METHODS: In two sessions, MRIs were acquired from fifteen healthy volunteers who were trained to be mechanically ventilated non-invasively We measured diaphragm motion amplitudes during FB and RB, the inter-quartile range (IQR) of the variation in average diaphragm position from one measurement over five consecutive DIBHs, and diaphragm cranial drift velocities during single PBHs from inhalation (PIBH) and exhalation (PEBH) breath-holds. RESULTS: RB significantly reduced the respiratory motion amplitude by 39%, from median (range) 20.9 (10.6-41.9) mm during FB to 12.8 (6.2-23.8) mm. The median IQR for variation in average diaphragm position over multiple DIBHs was 4.2 (1.0-23.6) mm. During single PIBHs with a median duration of 7.1 (2.0-11.1) minutes, the median diaphragm cranial drift velocity was 3.0 (0.4-6.5) mm/minute. For PEBH, the median duration was 5.8 (1.8-10.2) minutes with 4.4 (1.8-15.1) mm/minute diaphragm drift velocity. CONCLUSIONS: Regularized breathing at a frequency of 22 brpm resulted in significantly smaller diaphragm motion amplitudes compared to free breathing. This would enable smaller treatment volumes in radiotherapy. Furthermore, prolonged breath-holding from inhalation and exhalation with median durations of six to seven minutes are feasible. TRIAL REGISTRATION: Medical Ethics Committee protocol NL.64693.018.18.

Fitness of Isidorella newcombi Following Multi-generational Cu Exposures: Mortality, Cellular Biomarkers and Life History Responses.

The effects of multigenerational Cu exposure on the freshwater gastropod Isidorella newcombi were investigated. Snails were exposed to a range of treatment-specific Cu concentrations in the parental to F2 generations, and a common Cu concentration in the F3 generation. In the parental to F2 generations, some general responses to 3 days Cu exposures included reduced survival and feeding in snails exposed to higher Cu concentrations. This suggested that the snails exposed to the high Cu concentration were experiencing Cu-induced stress that may apply selection pressure. In the F3 generation, when all treatments were exposed to a common Cu concentration, increased survival was correlated with the pre-exposure Cu concentration history. Snails that had been pre-exposed to Cu also displayed reduced stress at a sub-lethal level, indicated by lower lysosomal destabilisation (LD). Mortality and LD responses in the F3 generation were not related to Cu tissue concentrations, indicating increased tolerance and reduced stress were not related to changes in Cu bioaccumulation. Total antioxidant capacity increased in the higher Cu concentration pre-exposure treatments which could be associated with lower Cu-induced stress, however, this is not supported by the oxidative damage marker lipid peroxidation, which also increased. While Cu tissue concentrations and oxidative stress markers were assessed to determine underlying reasons for increased tolerance in snails from a population with a multi-generational exposure history to Cu, the results were not conclusive. Despite this, it was demonstrated through increased survival and reduced LD that Cu tolerance can develop over a short evolutionary time scale.

An ancient, Antarctic-specific species complex: large divergences between multiple Antarctic lineages of the tardigrade genus Mesobiotus.

Antarctica has been isolated and progressively glaciated for over 30 million years, with only approximately 0.3 % of its area currently ice-free and capable of supporting terrestrial ecosystems. As a result, invertebrate populations have become isolated and fragmented, in some cases leading to speciation. Terrestrial invertebrate species currently found in Antarctica often show multi-million year, and even Gondwanan, heritage, with little evidence of recent colonisation. Mesobiotus is a globally distributed tardigrade genus. It has commonly been divided into two "groups", referred to as harmsworthi and furciger, with both groups currently considered cosmopolitan, with global reports including from both the Arctic and the Antarctic. However, some authors considered that Meb. furciger, as originally described, may represent an Antarctic-specific lineage. Using collections of tardigrades from across the Antarctic continent and publicly available sequences obtained from online databases, we use mitochondrial and nuclear ribosomal sequence data to clarify the relationships of Antarctic Mesobiotus species. Our analyses show that all Antarctic members belong to a single lineage, evolving separately from non-Antarctic representatives. Within this Antarctic lineage there are further deep divisions among geographic regions of the continent, consistent with the presence of a species complex. Based on our data confirming the deep divisions between this Antarctic lineage, which includes representatives of both groups, we recommend that the use of furciger and harmsworthi group terminology is now abandoned, as it leads to systematic and biogeographical confusion.

Duloxetine in OsteoArthritis (DOA) study: effects of duloxetine on pain and function in end-stage hip and knee OA - a pragmatic enriched randomized controlled trial.

BACKGROUND: Some osteoarthritis (OA) patients experience inadequate pain relief from analgesics like acetaminophen and nonsteroidal anti-inflammatory drugs. This could be the result of experienced non-nociceptive centralized pain. Placebo-controlled randomized trials (RCT) have proven the effectiveness of duloxetine for OA and several chronic pain conditions where central sensitization (CS) is one of the key underlying pain mechanisms. OBJECTIVES: Assess the efficacy of an 8-week duloxetine treatment compared to usual care in end-stage knee and hip OA patients with a level of centralized pain. DESIGN: Pragmatic, enriched, open-label RCT. METHODS: Patients were randomized to duloxetine or to care-as-usual. Primary outcome was pain in the index joint, measured with the pain domain of the Knee injury and Osteoarthritis Outcome Score (KOOS) or the Hip disability and Osteoarthritis Outcome Score (HOOS). The intention-to-treat principle was used, with mixed-model repeated measures to analyze the effect. RESULTS: One hundred eleven patients were randomized. Nearly 44% felt much to very much better after duloxetine usage compared to 0% in the care-as-usual group (p < 0.001). The duloxetine group scored 11.3 points (95%CI: 5.8, 16.8) better on the pain domain of the KOOS/HOOS (p < 0.001). Knee patients improved significantly more than hip patients (18.7 [95%CI: 11.3, 26.1] versus 6.0 [95%CI: - 2.6, 14.5] points better). CONCLUSIONS: Adding duloxetine treatment seems to be beneficial for end-stage knee OA patients with neuropathic-like symptoms (at risk of CS). End stage Hip OA patients seem to be nonresponsive to duloxetine. TRIAL REGISTRATION: Dutch Trial Registry with number NTR 4744 (15/08/2014) and in the EudraCT database with number 2013-004313-41 .

[Suturing basic procedural skills training for medical students during COVID-19 pandemic]. / Entrenamiento procedimental básico (EPROBA) en suturas para estudiantes de medicina durante pandemia por SARS-CoV-2 (COVID-19).

BACKGROUND: The adoption of sanitary measures due to the SARS-CoV-2 pandemic hampered teaching and learning methods in medicine. AIM: To communicate the results of a wound suture training workshop, based on the Basic Procedural Skills Training methodology and adapted to the pandemic context. MATERIAL AND METHODS: One hundred fourteen students were randomized in small groups due to sanitary measures and trained with a modification of the Basic Procedural Skills Training methodology. An informed consent was obtained from every student. The suturing skills were evaluated before and after the intervention with "The Objective Structured Assessment Of Technical Skills" (OSATS) instrument. The perception of the workshop and the implementation of the COVID-19 prevention measures were also evaluated. RESULTS: The students showed a statistically significant improvement after the intervention. In the OSATS verification list, the average score increased from 4.5 to 8.6 (p < 0.01). In the OSATS global scale, the average score increased from 13.0 to 25.3 (p < 0.01). The perception of the workshop and the prevention measures were well evaluated. CONCLUSIONS: Despite all the limitations of the pandemic context, we achieved a significant improvement after the intervention and a very good perception by the students.

Physical work exposure matrix for use in the UK Biobank.

BACKGROUND: UK Biobank (UKB) is a large prospective cohort capturing numerous health outcomes, but limited occupational information (job title, self-reported manual work and occupational walking/standing). AIMS: To create and evaluate validity of a linkage between UKB and a job exposure matrix for physical work exposures based on the US Occupational Information Network (O*NET) database. METHODS: Job titles and UK Standard Occupational Classification (SOC) codes were collected during UKB baseline assessment visits. Using existing crosswalks, UK SOC codes were mapped to US SOC codes allowing linkage to O*NET variables capturing numerous dimensions of physical work. Job titles with the highest O*NET scores were assessed to evaluate face validity. Spearman's correlation coefficients were calculated to compare O*NET scores to self-reported UKB measures. RESULTS: Among 324 114 participants reporting job titles, 323 936 were linked to O*NET. Expected relationships between scores and self-reported measures were observed. For static strength (0-7 scale), the median O*NET score was 1.0 (e.g. audiologists), with a highest score of 4.88 for stone masons and a positive correlation with self-reported heavy manual work (Spearman's coefficient = 0.50). For time spent standing (1-5 scale), the median O*NET score was 2.72 with a highest score of 5 for cooks and a positive correlation with self-reported occupational walking/standing (Spearman's coefficient = 0.56). CONCLUSIONS: While most jobs were not physically demanding, a wide range of physical work values were assigned to a diverse set of jobs. This novel linkage of a job exposure matrix to UKB provides a potentially valuable tool for understanding relationships between occupational exposures and disease.

Temperature Tides Across the Mid-Latitude Summer Turbopause Measured by a Sodium Lidar and MIGHTI/ICON.

Local full diurnal coverage of temperature variations across the turbopause (~90-115 km altitude) is achieved by combining the nocturnal observations of a Sodium (Na) Doppler lidar on the Utah State University (USU) campus (41.7°N, 248.2°E) and NASA Michelson interferometer for global high-resolution thermospheric imaging (MIGHTI)/Ionospheric connection explorer (ICON) daytime observations made in the same vicinity. In this study, utilizing this hybrid data set during summer 2020 between June 12th and July 15th, we retrieve the temperature signatures of diurnal and semidiurnal tides in this region. The tidal amplitudes of both components have similar vertical variation with increasing altitude: less than 5 K below ~98 km but increase considerably above, up to 19 K near 104 km. Both experience significant dissipation near turbopause altitudes, down to ~12 K up to 113 km for the diurnal tide and ~13 K for the semidiurnal tide near 110 km. In addition, while the semidiurnal tidal behavior is consistent with the theoretical predictions, the diurnal amplitude is considerably larger than what is expected in the turbopause region. The tidal phase profile shows a dominance of tidal components with a long vertical wavelength (longer than 40 km) for the semidiurnal tide. On the other hand, the diurnal tide demonstrates close to an evanescent wave behavior in the turbopause region, which is absent in the model results and Thermosphere ionosphere mesosphere energetics and dynamics (TIMED)/Sounding of the atmosphere using broadband radiometry (SABER) observations.

Shift work amongst older UK workers and job exit.

BACKGROUND: Night/shift work may be increasing but there are few data about the prevalence amongst older workers. With governments encouraging people to work to older ages, it is important to know how feasible night/shift work is for them and whether there are any adverse health consequences. AIMS: Amongst current older workers (aged 50-64 years), to explore the prevalence of night/shift working and evaluate its health impacts and sustainability over 4 years of follow-up. METHODS: Data from the Health and Employment After Fifty cohort were used to describe the demographic, job and health characteristics of men and women undertaking night/shift work. Longitudinal data were used to examine the number and nature of exits annually thereafter. RESULTS: Amongst the 5409 working at baseline, 32% reported night/shift work in sectors which differed by sex. Night/shift workers were more likely to be: current smokers; doing physically demanding work; struggling to cope at work; dissatisfied with their hours; depressed; sleeping poorly; rating their health poorly. Women whose job involves night work were more likely to exit the workforce over 4 years. CONCLUSIONS: Almost one in three contemporary UK older workers report night/shift work. We found some evidence of adverse impacts on health, sleep and well-being and higher rates of job exit amongst women. More research is needed but night/shift work may be challenging to sustain for older workers and could have health consequences.

An Allogeneic Multiple Myeloma GM-CSF-Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission.

PURPOSE: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). PATIENTS AND METHODS: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. RESULTS: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27-DNAM1-CD8+ T cells and antigen-presenting cells was associated with disease progression. CONCLUSIONS: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.

Secondary flow in bifurcations - Important effects of curvature, bifurcation angle and stents.

Coronary bifurcations have complex flow patterns including secondary flow zones and helical flow, which directly affect pathophysiological mechanisms such as the development of atherosclerosis. The objective of this study was to generate insights into the effects of curvature, bifurcation angle and the presence of stents on flow patterns and resulting haemodynamics in coronary left main bifurcations. The blood flow and associated metrics were modelled in both idealised and patient-specific bifurcations with varying curvature and bifurcation angles with and without stents, resulting in a total of 128 geometries considered. The results showed that larger curvature of bifurcating vessels has a significant influence on secondary flow, especially with distance to the bifurcation region, causing a skew, spin and asymmetry of Dean vortices, an increase in helical flow intensity with symmetry loss, and a decrease in adversely low time-average wall shear stress (TAWSS). Generally, asymmetric flow patterns coincided with adversely low TAWSS regions. In identical stented geometries, the presence of the stents induced local recirculation immediately adjacent to the stent struts, thus generating adversely low TAWSS in these areas, with some effect on the overall secondary flow. Overall, the effect of stents outweighed the effect of curvature and BA. This new knowledge contributes to a better understanding of the joint effects of curvature, bifurcation angle, and stents on flow patterns and haemodynamics in coronary bifurcations.

Rol de conocimientos previos en los resultados de un programa de entrenamiento en sutura de heridas para estudiantes de medicina mediante metodología EPROBA / Role of previous knowledge in the results of a training program in wound suturing for medical students using EPROBA methodology

Resumen Objetivo: Comparar la adquisición de habilidades quirúrgicas básicas en estudiantes de medicina según el tipo de instrucción teórico-práctica recibida previo a un taller estandarizado de sutura de heridas. Materiales y Método: Estudio cuasiexperimental antes-después para estudiantes de cuarto año durante el 2018. Se realizó taller de sutura de heridas aplicado en modelo biológico (pata de cerdo), previo consentimiento informado y aprobación Comité Ético Científico. Mediante instrumento "The Objective Structured Assessment Of Technical Skills" (OSATS) se evaluó técnica de sutura antes y después del entrenamiento. Se dividió a los participantes según conocimientos previos al taller: Grupo A: recibió instrucción teórico-práctica en pacientes in vivo. Grupo B: recibió instrucción teórico-práctica en modelos de simulación. Grupo C: sin conocimientos previos en suturas. Se evaluó percepción de estudiantes mediante encuesta validada. Se comparó puntaje OSATS antes-después del taller y encuesta de percepción según grupo, utilizando SPSS24® y ANOVA. Se consideró significativo p < 0,05. Resultados: Se evaluaron 124 estudiantes. Grupo A: 17 (13,7%); Grupo B: 38 (30,7%); Grupo C: 69 (55,6%) respectivamente. Existió diferencia en puntaje OSATS de ingreso al taller Grupo A: 19,4 ± 4,9; Grupo B: 13,7 ± 6,3; Grupo C: 11,1 ± 4,5 (p < 0,05). Puntaje OSATS finalizada la intervención Grupo A: 28,8 ± 1,5; Grupo B: 28,0 ± 1,9; Grupo C: 27,9 ± 2,2 (p = 0,48), sin diferencia significativa. La intervención fue bien percibida, sin diferencias significativas entre grupos. Discusión: El resultado de evaluación OSATS finalizado el taller es independiente de experiencias, instrucción teórico-práctica o conocimientos previos a la intervención. Conclusión: Los programas de entrenamiento con evaluación estandarizada pueden equiparar los resultados entre estudiantes con diferentes conocimientos previos.

Aim: To compare the learning of basic surgical skills among medical students according to the type of theoretical and practical instruction they had prior to a standardized wound suturing workshop. Materials and Method: Quasi-experimental before and after study intended to fourth year students for the 2018. The wound suturing workshop was carried out with help of a biological model (pork leg), prior to an informed consent and the approval of the Ethics Committee. The suturing skills were evaluated by the tool "The Objective Structured Assessment Of Technical Skills" (OSATS) before and after the training. All of the participating students were sorted in groups by their previous surgical knowledge: Group A: received theoretical and practical instruction in patients. Group B: received theoretical and practical instruction in simulation models. Group C: without previous suturing knowledge. The students perception was evaluated by a validated survey. The OSATS score before and after the workshop and the perception survey were compared between the groups, using SPSS24® and ANOVA. p < 0,05 was considered significant. Results: 124 students were evaluated. Group A: 17 (13.7%); Group B: 38 (30.7%); Group C: 69 (55.6%) accordingly. There was a OSATS score difference before the workshop Group A: 19.4 ± 4,9; Group B: 13.7 ± 6.3; Group C: 11.1 ± 4.5 (p < 0.05). OSATS score after the intervention Group A: 28.8 ± 1.5; Group B: 28.0 ± 1.9; Group C: 27.9 ± 2.2 (p = 0.48), without a significant difference. The intervention was well perceived, without significant differences among the groups. Discussion: The OSATS score post workshop is independent of experiences, theoretical and practical instruction or previous knowledge. Conclusion: Training programs with standardized evaluation can even out the results among students with different previous knowledge.