The association between frailty and survival in patients with pleural disease: a retrospective cohort study.

BACKGROUND: There are currently no data on the relationship between frailty and mortality in pleural disease. Understanding the relationship between frailty and outcomes is increasingly important for clinicians to guide decisions regarding investigation and management. This study aims to explore the relationship between all-cause mortality and frailty status in patients with pleural disease. METHODS: In this retrospective analysis of a prospectively collected observational cohort study, outpatients presenting to the pleural service at a tertiary centre in Bristol, UK with a radiologically confirmed, undiagnosed pleural effusion underwent comprehensive assessment and were assigned a final diagnosis at 12 months. The modified frailty index (mFI) was calculated and participants classified as frail (mFI ≥ 0.4) or not frail (mFI ≤ 0.2). RESULTS: 676 participants were included from 3rd March 2008 to 29th December 2020. The median time to mortality was 490 days (IQR 161-1595). A positive association was found between 12-month mortality and frailty (aHR = 1.72, 95% CI 1.02-2.76, p = 0.025) and age ≥ 80 (aHR = 1.80, 95% CI 1.24-2.62, p = 0.002). Subgroup analyses found a stronger association between 12-month mortality and frailty in benign disease (aHR = 4.36, 95% CI 2.17-8.77, p < 0.0001) than in all pleural disease. Malignancy irrespective of frailty status was associated with an increase in all-cause mortality (aHR = 10.40, 95% CI 6.01-18.01, p < 0.0001). CONCLUSION: This is the first study evaluating the relationship between frailty and outcomes in pleural disease. Our data demonstrates a strong association between frailty and 12-month mortality in this cohort. A malignant diagnosis is an independent predictor of 12-month mortality, irrespective of frailty status. Frailty was also strongly associated with 12-month mortality in patients with a benign underlying cause for their pleural disease. This has clinical relevance for pleural physicians; evaluating patients' frailty status and its impact on mortality can guide clinicians in assessing suitability for invasive investigation and management. TRIAL REGISTRATION: This study is registered with the Health Research Authority (REC reference 08/H0102/11) and the NIHR Portfolio (Study ID 8960).

Downsized: gray whales using an alternative foraging ground have smaller morphology.

Describing individual morphology and growth is key for identifying ecological niches and monitoring the health and fitness of populations. Eastern North Pacific ((ENP), approximately 16 650 individuals) gray whales primarily feed in the Arctic/sub-Arctic regions, while a small subgroup called the Pacific Coast Feeding Group (PCFG, approximately 212 individuals) instead feeds between northern California, USA and British Columbia, Canada. Evidence suggests PCFG whales have lower body condition than ENP whales. Here we investigate morphological differences (length, skull, and fluke span) and compare length-at-age growth curves between ENP and PCFG whales. We use ENP gray whale length-at-age data comprised of strandings, whaling, and aerial photogrammetry (1926-1997) for comparison to data from PCFG whales collected through non-invasive techniques (2016-2022) to estimate age (photo identification) and length (drone-based photogrammetry). We use Bayesian methods to incorporate uncertainty associated with morphological measurements (manual and photogrammetric) and age estimates. We find that while PCFG and ENP whales have similar growth rates, PCFG whales reach smaller asymptotic lengths. Additionally, PCFG whales have relatively smaller skulls and flukes than ENP whales. These findings represent a striking example of morphological adaptation that may facilitate PCFG whales accessing a foraging niche distinct from the Arctic foraging grounds of the broader ENP population.

CsAr, CsXe, and RbXe B2Σ1/2+ Interatomic Potentials Determined from Absorption Spectra and Calculations of Franck-Condon Factors for Free-Free Optical Transitions of Atomic Collision Pairs.

Interatomic potentials for the B2Σ1/2+ states of CsAr, CsXe, and RbXe have been determined through comparisons of experimental B ← X absorption spectra for alkali vapor-rare gas mixtures with calculations of the Franck-Condon factors (FCFs) associated with free-free transitions of thermal atomic pairs. Simulations of optical transitions of alkali-rare gas atomic pairs between the thermal and vibrational continua of the X2Σ1/2+ and B2Σ1/2+ states of the molecule, responsible for the blue satellites of the Cs and Rb D2 resonance lines in a rare gas background, require the incorporation of ground-state J values above ∼400 into the FCF calculations and proper normalization of the free-particle wave functions. Absorption spectra computed on the basis of several X and B state interatomic potentials available in the literature were found to be sensitive to the height of the B2Σ1/2+ state barrier, as well as the X2Σ1/2+ state repulsive wall contour and the location of the van der Waals minimum. Other spectral simulations entailed iterative modifications to a selected B2Σ1/2+ interatomic potential, again coupled with comparison to experimental B ← X spectra. Comparisons of calculated spectra with experiment yield a CsXe B2Σ1/2+ potential, for example, exhibiting a barrier height of 76 cm-1 at 5.2 Å and yet is nearly flat at smaller values of internuclear separation (R). The latter contrasts with previous theoretical calculations of VB(R) in the vicinity of the barrier maximum. For the CsAr molecule, the B2Σ1/2+ barrier height was found to be 221 cm-1, which is within 3% of the value determined from pseudopotential calculations incorporating the spin-orbit effect. Reproducing Cs-rare gas experimental absorption spectra also requires the existence of a broad, shallow potential well lying beyond the B2Σ1/2+ barrier that, for CsAr, has a dissociation energy (De ∼ 24 cm-1) a factor of 3 larger than values predicted by theory. Similar results are obtained for the RbXe and CsXe complexes.

Comparison of the Aotearoa New Zealand Early Warning Score and National Early Warning Score to predict adverse inpatient events in a vital sign dataset.

Aotearoa New Zealand uses a single early warning score (EWS) across all public and private hospitals to detect adult inpatient physiological deterioration. This combines the aggregate weighted scoring of the UK National Early Warning Score with single parameter activation from Australian medical emergency team systems. We conducted a retrospective analysis of a large vital sign dataset to validate the predictive performance of the New Zealand EWS in discriminating between patients at risk of serious adverse events and compared this with the UK EWS. We also compared predictive performance for patients admitted under medical vs. surgical specialties. A total of 1,738,787 aggregate scores (13,910,296 individual vital signs) were obtained from 102,394 hospital admissions to six hospitals within the Canterbury District Health Board of New Zealand's South Island. Predictive performance of each scoring system was determined using area under the receiver operating characteristic curve. Analysis showed that the New Zealand EWS is equivalent to the UK EWS in predicting patients at risk of serious adverse events (cardiac arrest, death and/or unanticipated ICU admission). Area under the receiver operating characteristic curve for both EWSs for any adverse outcome was 0.874 (95%CI 0.871-0.878) and 0.874 (95%CI 0.870-0.877), respectively. Both EWSs showed superior predictive value for cardiac arrest and/or death in patients admitted under surgical rather than medical specialties. Our study is the first validation of the New Zealand EWS in predicting serious adverse events in a broad dataset and supports previous work showing the UK EWS has superior predictive performance in surgical rather than medical patients.

Informing the management of multiple stressors on estuarine ecosystems using an expert-based Bayesian Network model.

The approach of applying stressor load limits or thresholds to aid estuarine management is being explored in many global case studies. However, there is growing concern regarding the influence of multiple stressors and their cumulative effects on the functioning of estuarine ecosystems due to the considerable uncertainty around stressor interactions. Recognising that empirical data limitations hinder parameterisation of detailed models of estuarine ecosystem responses to multiple stressors (suspended sediment, sediment mud and metal content, and nitrogen inputs), an expert driven Bayesian network (BN) was developed and validated. Overall, trends in estuarine condition predicted by the BN model were well supported by field observations, including results that were markedly higher than random (71-84% concordance), providing confidence in the overall model dynamics. The general BN framework was then applied to a case study estuary to demonstrate the model's utility for informing management decisions. Results indicated that reductions in suspended sediment loading were likely to result in improvements in estuarine condition, which was further improved by reductions in sediment mud and metal content, with an increased likelihood of high abundance of ecological communities relative to baseline conditions. Notably, reductions in suspended sediment were also associated with an increased probability of high nuisance macroalgae and phytoplankton if nutrient loading was not also reduced (associated with increased water column light penetration). Our results highlight that if stressor limit setting is to be implemented, limits must incorporate ecosystem responses to cumulative stressors, consider the present and desired future condition of the estuary of interest, and account for the likelihood of unexpected ecological outcomes regardless of whether the experts (or empirical data) suggest a threshold has or has not been triggered.

Increased care at discharge from COVID-19: The association between pre-admission frailty and increased care needs after hospital discharge; a multicentre European observational cohort study.

BACKGROUND: The COVID-19 pandemic has placed significant pressure on health and social care. Survivors of COVID-19 may be left with substantial functional deficits requiring ongoing care. We aimed to determine whether pre-admission frailty was associated with increased care needs at discharge for patients admitted to hospital with COVID-19. METHODS: Patients were included if aged over 18 years old and admitted to hospital with COVID-19 between 27 February and 10 June 2020. The Clinical Frailty Scale (CFS) was used to assess pre-admission frailty status. Admission and discharge care levels were recorded. Data were analysed using a mixed-effects logistic regression adjusted for age, sex, smoking status, comorbidities, and admission CRP as a marker of severity of disease. RESULTS: Thirteen hospitals included patients: 1671 patients were screened, and 840 were excluded including, 521 patients who died before discharge (31.1%). Of the 831 patients who were discharged, the median age was 71 years (IQR, 58-81 years) and 369 (44.4%) were women. The median length of hospital stay was 12 days (IQR 6-24). Using the CFS, 438 (47.0%) were living with frailty (≥ CFS 5), and 193 (23.2%) required an increase in the level of care provided. Multivariable analysis showed that frailty was associated with an increase in care needs compared to patients without frailty (CFS 1-3). The adjusted odds ratios (aOR) were as follows: CFS 4, 1.99 (0.97-4.11); CFS 5, 3.77 (1.94-7.32); CFS 6, 4.04 (2.09-7.82); CFS 7, 2.16 (1.12-4.20); and CFS 8, 3.19 (1.06-9.56). CONCLUSIONS: Around a quarter of patients admitted with COVID-19 had increased care needs at discharge. Pre-admission frailty was strongly associated with the need for an increased level of care at discharge. Our results have implications for service planning and public health policy as well as a person's functional outcome, suggesting that frailty screening should be utilised for predictive modelling and early individualised discharge planning.

Association between preadmission frailty and care level at discharge in older adults undergoing emergency laparotomy.

BACKGROUND: Older adults undergoing emergency abdominal surgery have significantly poorer outcomes than younger adults. For those who survive, the level of care required on discharge from hospital is unknown and such information could guide decision-making. The ELF (Emergency Laparotomy and Frailty) study aimed to determine whether preoperative frailty in older adults was associated with increased dependence at the time of discharge. METHODS: The ELF study was a UK-wide multicentre prospective cohort study of older patients (65 years or more) undergoing emergency laparotomy during March and June 2017. The objective was to establish whether preoperative frailty was associated with increased care level at discharge compared with preoperative care level. The analysis used a multilevel logistic regression adjusted for preadmission frailty, patient age, sex and care level. RESULTS: A total of 934 patients were included from 49 hospitals. Mean(s.d.) age was 76·2(6·8) years, with 57·6 per cent women; 20·2 per cent were frail. Some 37·4 per cent of older adults had an increased care level at discharge. Increasing frailty was associated with increased discharge care level, with greater predictive power than age. The adjusted odds ratio for an increase in care level was 4·48 (95 per cent c.i. 2·03 to 9·91) for apparently vulnerable patients (Clinical Frailty Score (CFS) 4), 5·94 (2·54 to 13·90) for those mildly frail (CFS 5) and 7·88 (2·97 to 20·79) for those moderately or severely frail (CFS 6 or 7), compared with patients who were fit. CONCLUSION: Over 37 per cent of older adults undergoing emergency laparotomy required increased care at discharge. Frailty scoring was a significant predictor, and should be integrated into all acute surgical units to aid shared decision-making and discharge planning.

ANTECEDENTES: Los adultos mayores sometidos a cirugía abdominal de urgencia tienen resultados significativamente peores que los adultos jóvenes. Para aquellos pacientes que sobreviven, el nivel de atención que requieren tras el alta hospitalaria se desconoce y esta información podría servir de guía en la toma de decisiones. El estudio ELF (Emergency Laparotomy and Frailty) tenía como objetivo determinar si la fragilidad preoperatoria en adultos mayores se asociaba con un aumento de la dependencia en el momento del alta. MÉTODOS: El estudio ELF era un estudio multicéntrico extenso efectuado en el Reino Unido (n = 49) que incluyó una cohorte prospectiva de 934 pacientes mayores (> 65 años) sometidos a laparotomía de urgencia durante marzo-junio de 2017. El objetivo fue establecer si la fragilidad preoperatoria aumentaba el nivel de asistencia en el momento del alta en comparación con el nivel de asistencia preoperatorio. Para el análisis se utilizó una regresión logística multinivel ajustada a características previas al ingreso: fragilidad, edad del paciente, género, y nivel de asistencia. RESULTADOS: La edad media de los pacientes fue 76,2 años (DE = 6,83), con un 57% de mujeres, un 20,2% de pacientes frágiles y un 37,4% de adultos mayores que presentaron un aumento en el nivel de asistencia en el momento del alta. Un aumento de la fragilidad se asoció con un incremento en el nivel de asistencia en el momento del alta (y mayor poder predictivo que la edad). La razón de oportunidades (odds ratio, OR) ajustada por el aumento del nivel de asistencia fue 4,48 (i.c. del 95% 2,03-9,91) para pacientes aparentemente vulnerables (Clinical Frailty Scale, CFS 4); 5,94 (i.c. del 95% 2,54-13,90) para aquellos ligeramente frágiles (CFS 5); y 7,88 (i.c. del 95% 2,97-20,79) para aquellos con fragilidad moderada o grave (CFS 6 and 7) en comparación con pacientes en buenas condiciones. CONCLUSIÓN: Este es el primer estudio que documenta que más del 37% de adultos mayores sometidos a laparotomía de urgencia precisaron un aumento en el nivel de asistencia en el momento del alta. La evaluación de la fragilidad debería integrarse en todas las unidades quirúrgicas de agudos para ayudar a compartir la toma de decisiones y los planes de tratamiento.

Risk factors for incident delirium among urological patients: a systematic review and meta-analysis with GRADE summary of findings.

BACKGROUND: Post-operative delirium is an important, yet under-researched complication of surgery. Patients undergoing urological surgery may be at especially high risk of POD, as they are often older, and interventions can be associated with conditions that trigger delirium. The main aim of this systematic review was to evaluate the available evidence for risk factors in this patient group. METHODS: Five databases were searched (MEDLINE, Web of Science, EMBASE, CINAHL and PsychInfo) between January 1987 and June 2019. The Newcastle-Ottawa Scale was used to assess for risk of bias. Pooled odds ratio or mean difference (MD) for individual risk factors were estimated using the Mantel-Haenzel and inverse variance methods. RESULTS: Seven articles met the inclusion criteria, giving a total population of 1937. The incidence of POD ranged from 5 to 29%. Three studies were deemed low risk of bias and four at a high risk of bias. Nine risk factors were suitable for meta-analysis, with age (MD 4.314 95% CI 1.597, 7.032 p = 0.002) and the clock drawing test (MD - 2.443 95% CI - 3.029, - 1.857 p < 0.001) having a statistically significant association with POD in pooled analyses. CONCLUSION: Delirium is common in urological patients. This review has identified a lack of studies in this surgical population, with wide heterogeneity and high risk of bias. It also highlights a number of potential risk factors for post-operative delirium, of which some are modifiable. However, the strength of evidence is weak at present and so future research should focus on assessing comparable risk factors in this patient group in order to inform future clinical practice. Review registration The review protocol was prospectively registered with the PROSPERO database (reference CRD42017054613).

Frailty predicts mortality in all emergency surgical admissions regardless of age. An observational study.

BACKGROUND: frail patients in any age group are more likely to die than those that are not frail. We aimed to evaluate the impact of frailty on clinical mortality, readmission rate and length of stay for emergency surgical patients of all ages. METHODS: a multi-centre prospective cohort study was conducted on adult admissions to acute surgical units. Every patient presenting as a surgical emergency to secondary care, regardless of whether they ultimately underwent a surgical procedure was included. The study was carried out during 2015 and 2016.Frailty was defined using the 7-point Clinical Frailty Scale. The primary outcome was mortality at Day 90. Secondary outcomes included: mortality at Day 30, length of stay and readmission within a Day 30 period. RESULTS: the cohort included 2,279 patients (median age 54 years [IQR 36-72]; 56% female). Frailty was documented in patients of all ages: 1% in the under 40's to 45% of those aged 80+. We found that each incremental step of worsening frailty was associated with an 80% increase in mortality at Day 90 (OR 1.80, 95% CI: 1.61-2.01) supporting a linear dose-response relationship. In addition, the most frail patients were increasingly likely to stay in hospital longer, be readmitted within 30 days, and die within 30 days. CONCLUSIONS: worsening frailty at any age is associated with significantly poorer patient outcomes, including mortality in unselected acute surgical admissions. Assessment of frailty should be integrated into emergency surgical practice to allow prognostication and implementation of strategies to improve outcomes.

Spin Polarization of Rb and Cs np

We report the selective population of Rb or Cs np ^{2}P_{3/2} (n=5, 6; F=4, 5) hyperfine states by the photodissociation of a transient, alkali-rare gas diatomic molecule. Circularly polarized (σ^{-}), amplified spontaneous emission (ASE) on the D_{2} line of Rb or Cs (780.0 and 852.1 nm, respectively) is generated when Rb-Xe or Cs-Xe ground state collision pairs are photoexcited by a σ^{+}-polarized optical field having a wavelength within the D_{2} blue satellite continuum, associated with the B^{2}Σ_{1/2}^{+}←X^{2}Σ_{1/2}^{+} (free←free) transition of the diatomic molecule. The degree of spin polarization of Cs (6p ^{2}P_{3/2}), specifically, is found to be dependent on the interatomic distance (R) at which the excited complex is born, a result attributed to the structure of the B^{2}Σ_{1/2}^{+} state. For Cs-Xe atomic pairs, tuning the wavelength of the optical field from 843 to 848 nm varies the degree of circular polarization of the ASE from 63% to almost unity because of the perturbation, in the 5≤R≤6 Å interval, of the ^{2}Σ_{1/2}^{+} potential by a dσ molecular orbital associated with a higher ^{2}Λ electronic state. Monitoring only the Cs 6p ^{2}P_{3/2} spin polarization reveals a previously unobserved interaction of CsXe (B^{2}Σ_{1/2}^{+}) with the lowest vibrational levels of a ^{2}Λ state derived from Cs (5d)+Xe. By inserting a molecular intermediate into the alkali atom excitation mechanism, these experiments realize electronic spin polarization through populating no more than two np ^{2}P_{3/2} hyperfine states, and demonstrate a sensitive spectroscopic probe of R-dependent state-state interactions and their impact on interatomic potentials.

FTIR imaging detects diet and genotype-dependent chemical composition changes in wild type and mutant C. elegans strains.

This study focuses on the use of Fourier Transform Infrared (FTIR) microspectroscopy to determine chemical changes induced in the nematode Caenorhabditis elegans by supplementation of C. elegans maintenance media (CeMM) by Eicosapentaenoic acid (EPA). Wild-type C. elegans (N2) and mutant strains (tub-1 and fat-3) were grown in CeMM alone, and CeMM supplemented with EPA at 25 or 100 µM. Feeding was performed for 72 h. FTIR imaging was performed in transmission mode on individual worms. The FTIR imaging analysis of wild-type animals revealed the presence of vibrations assigned to unsaturated fatty acids, specifically bands at 3008 cm-1 ([double bond, length as m-dash]C-H, olefinic stretch) and 1744 cm-1 (C[double bond, length as m-dash]O, unsaturated fatty acids). It confirmed previously reported synthesis of unsaturated fatty acids in wild-type C. elegans. For the FTIR spectra of mutant strains, these vibrations were absent or present only as very small shoulder, which indicates that tub-1 and fat-3 synthesize essentially saturated fatty acids as indicated by the presence of -CH2 and C[double bond, length as m-dash]O vibrations. These results are in agreement with previous studies which reported that these mutants have altered lipid compositions. Principal component analysis showed differences in chemical composition between wild-type and mutant strains as well as between mutant strains cultured in normal CeMM and those cultured in CeMM supplemented with EPA. This study demonstrated the usefulness of FTIR microspectroscopy to investigate fat metabolism in C. elegans.

Systematic review and meta-analysis of risk factors for postoperative delirium among older patients undergoing gastrointestinal surgery.

BACKGROUND: Postoperative delirium (POD) is common after surgery. As age is a known risk factor, the increased ageing of the population undergoing surgery emphasizes the importance of the subject. Knowledge of other potential risk factors in older patients with surgical gastrointestinal diseases is lacking. The aim here was to collate and synthesize the published literature on risk factors for delirium in this group. METHODS: Five databases were searched (MEDLINE, Web of Science, Embase, CINAHL(®) and PSYCinfo(®) ) between January 1987 and November 2014. The Newcastle-Ottawa Scale was used to rate study quality. Pooled odds ratios or mean differences for individual risk factors were estimated using the Mantel-Haenszel and inverse-variance methods. RESULTS: Eleven studies met the inclusion criteria; they provided a total of 1427 patients (318 with delirium and 1109 without), and predominantly included patients undergoing elective colorectal surgery. The incidence of POD ranged from 8·2 to 54·4 per cent. A total of 95 risk factors were investigated, illustrating wide heterogeneity in study design. Seven statistically significant risk factors were identified in pooled analysis: old age, American Society of Anesthesiologists (ASA) physical status grade at least III, body mass index, lower serum level of albumin, intraoperative hypotension, perioperative blood transfusion and history of alcohol excess. Patients with POD had a significantly increased duration of hospital stay and a higher mortality rate compared with those without delirium. CONCLUSION: Delirium is common in older patients undergoing gastrointestinal surgery. Several risk factors were consistently associated with POD.

HbA1c measurement and relationship to incident stroke.

AIMS: To determine the proportion of people with diabetes who have HbA1c measured, what proportion achieve an HbA1c level of < 58 mmol/mol (7.5%), the frequency of testing and if there was any change in HbA1c level in the year before and the year after an incident stroke. METHODS: This study used the Secure Anonymised Information Linkage (SAIL) databank, which stores hospital data for the whole of Wales and ~ 65% of Welsh general practice records, to identify cases of stroke in patients with diabetes between 2000 and 2010. These were matched against patients with diabetes but without stroke disease. We assessed the frequency of HbA1c testing and change in HbA1c in the first year after stroke. Estimation was made of the proportion of patients achieving an HbA1c measurement ≤ 58 mmol/mol (7.5%). RESULTS: There were 1741 patients with diabetes and stroke. Of these, 1173 (67.4%) had their HbA1c checked before their stroke and 1137 (65.3%) after their stroke. In the control group of 16 838 patients with diabetes but no stroke, 8413 (49.9%) and 9288 (55.1%) had their HbA1c checked before and after the case-matched stroke date, respectively. In patients with diabetes and stroke, HbA1c fell from 61-56 mmol/mol (7.7-7.3%) after their stroke (P < 0.001). Before the study, 55.0% of patients with stroke had an HbA1c ≥ 58 mmol/mol compared with 65.2% of control patients, these figures were 62.5% and 65.3% after the stroke. CONCLUSIONS: The frequency of diabetes testing was higher in patients who had experienced a stroke before and after their incident stroke compared with control patients but did not increase after their stroke. Glucose control improved significantly in the year after a stroke.

Emergence of a novel GII.17 norovirus ­ End of the GII.4 era?

In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.

Stability and change of genetic and environmental effects on the common liability to alcohol, tobacco, and cannabis DSM-IV dependence symptoms.

This study investigated the stability of genetic and environmental effects on the common liability to alcohol, tobacco, and cannabis dependence across adolescence and young adulthood. DSM-IV symptom counts from 2,361 adolescents were obtained using a structured diagnostic interview. Several sex-limited longitudinal common pathway models were used to examine gender differences in the magnitude of additive genetic (A), shared environment, and non-shared environmental effects over time. Model fitting indicated limited gender differences. Among older adolescents (i.e., age > 14), the heritability of the latent trait was estimated at 0.43 (0.05, 0.94) during the first wave and 0.63 (0.21, 0.83) during the second wave of assessment. A common genetic factor could account for genetic influences at both assessments, as well as the majority of the stability of SAV over time [rA = 1.00 (0.55, 1.00)]. These results suggest that early genetic factors continue to play a key role at later developmental stages.

Multiple outbreaks of a novel norovirus GII.4 linked to an infected post-symptomatic food handler.

Multiple norovirus outbreaks following catered events in Auckland, New Zealand, in September 2010 were linked to the same catering company and investigated. Retrospective cohort studies were undertaken with attendees of two events: 38 (24·1%) of 158 surveyed attendees developed norovirus-compatible illness. Attendees were at increased risk of illness if they had consumed food that had received manual preparation following cooking or that had been prepared within 45 h following end of symptoms in a food handler with prior gastroenteritis. All food handlers were tested for norovirus. A recombinant norovirus GII.e/GII.4 was detected in specimens from event attendees and the convalescent food handler. All catering company staff were tested; no asymptomatic norovirus carriers were detected. This investigation improved the characterization of norovirus risk from post-symptomatic food handlers by narrowing the potential source of transmission to one individual. Food handlers with gastroenteritis should be excluded from the workplace for 45 h following resolution of symptoms.

Indications for worldwide increased norovirus activity associated with emergence of a new variant of genotype II.4, late 2012.

Globally, surveillance systems showed an increasein norovirus activity in late 2012. Molecular datashared through the NoroNet network suggest thatthis increase is related to the emergence of a newnorovirus genotype II.4 variant, termed Sydney 2012.Healthcare institutions are advised to be prepared fora severe norovirus season.

Blood conservation strategies reduce the need for transfusions in ascending and aortic arch surgery.

INTRODUCTION: Ascending and aortic arch surgery is associated with higher levels of blood loss and subsequent need for allogeneic blood transfusions. We hypothesized that aggressive, comprehensive blood conservation strategies may limit the need for transfusions and, subsequently, improve postoperative outcomes. METHODS: Over a five-year period, 189 patients underwent proximal aortic surgery at our institution. Fifty-one patients underwent surgery using a comprehensive blood conservation strategy (BCS), including preoperative hemoglobin optimization, antifibrinolytic therapy, intraoperative acute normovolemic hemodilution, cell salvage and meticulous surgical technique. The remaining 138 patients underwent surgery using conventional techniques (CONV). RESULTS: Patients in the BCS group required fewer transfusions during their hospital stay compared to the conventional group (56.9% vs. 72.5%, p=0.041). When examining elective cases, this trend widens, with 40.0% of BCS patients requiring any transfusions compared to 72.9% patients in the conventional group (p=0.001). Red cell (47.1% vs. 62.3%, p=0.06), plasma (43.1% vs. 61.6%, p=0.02) and platelets (27.5% vs. 47.8%, p=0.01) were also less frequently required in the BCS group than the conventional group, respectively. When a transfusion was required, patients in the BCS group received significantly fewer units of red blood cells (2.8 ± 7.0 units) than the conventional group (5.81 ± 9.5 units; p=0.039). Mortality was similar in both groups (BCS 7.8%, conventional 10.9%, p=0.54); however, there was significantly less morbidity in the BCS group, using a composite of any of 10 major postoperative complications (23.5% vs. 39.1%; p=0.046). Median intensive care unit (ICU) and hospital lengths of stay were 2 and 7 days in the BCS group and 2 and 8 days in the CONV group (p=0.15), respectively. CONCLUSIONS: The aggressive use of a comprehensive blood conservation strategy in ascending and aortic arch surgery can significantly reduce the need for blood transfusions and is associated with less postoperative morbidity. Further evaluation with a randomized, controlled trial is warranted.

Mutant glycosyltransferase and altered glycosylation of alpha-dystroglycan in the myodystrophy mouse.

Spontaneous and engineered mouse mutants have facilitated our understanding of the pathogenesis of muscular dystrophy and they provide models for the development of therapeutic approaches. The mouse myodystrophy (myd) mutation produces an autosomal recessive, neuromuscular phenotype. Homozygotes have an abnormal gait, show abnormal posturing when suspended by the tail and are smaller than littermate controls. Serum creatine kinase is elevated and muscle histology is typical of a progressive myopathy with focal areas of acute necrosis and clusters of regenerating fibers. Additional aspects of the phenotype include sensorineural deafness, reduced lifespan and decreased reproductive fitness. The myd mutation maps to mouse chromosome 8 at approximately 33 centimorgans (cM) (refs. 2, 4-7). Here we show that the gene mutated in myd encodes a glycosyltransferase, Large. The human homolog of this gene (LARGE) maps to chromosome 22q. In myd, an intragenic deletion of exons 4-7 causes a frameshift in the resultant mRNA and a premature termination codon before the first of the two catalytic domains. On immunoblots, a monoclonal antibody to alpha-dystroglycan (a component of the dystrophin-associated glycoprotein complex) shows reduced binding in myd, which we attribute to altered glycosylation of this protein. We speculate that abnormal post-translational modification of alpha-dystroglycan may contribute to the myd phenotype.