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BACKGROUND: Dual anti-human epidermal growth factor receptor 2 (HER2) blockade has improved the outcomes of patients with early and metastatic HER2-positive breast cancer. Here we present the final 10-year analysis of the ALTTO trial. PATIENTS AND METHODS: The ALTTO trial (NCT00490139) is a prospective randomized, phase III, open-label, multicenter study that investigated the role of adjuvant chemotherapy and trastuzumab alone, in combination or sequentially with lapatinib. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), time to distant recurrence and safety. RESULTS: Overall, 6281 patients with HER2-positive early breast cancer were included in the final efficacy analysis in three treatment groups: trastuzumab (T), lapatinib + trastuzumab (L + T) and trastuzumab followed by lapatinib (TâL). Baseline characteristics were well balanced between groups. At a median follow-up of 9.8 years, the addition of lapatinib to trastuzumab and chemotherapy did not significantly improve DFS nor OS. The 10-year DFS was 77% in T, 79% in L + T and 79% in TâL, and the 10-year OS was 87%, 89% and 89%, respectively. The incidence of any cardiac event was low and similar in the three treatment groups. CONCLUSIONS: With a longer follow-up, no significant improvement was observed in DFS in patients treated with dual anti-HER2 blockade with lapatinib + trastuzumab compared to trastuzumab alone. The 10-year survival rates for the combination group are consistent with other studies that have explored dual anti-HER2 therapy.
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Objectives: To evaluate the impact of homelessness on surgical outcomes following ankle fracture surgery. Design: Retrospective cohort study. Setting: Mariner claims database. Patients/Participants: Patients older than 18 years who underwent open reduction and internal fixation (ORIF) of ankle fractures between 2010 and 2021. A total of 345,759 patients were included in the study. Intervention: Study patients were divided into two cohorts (homeless and nonhomeless) based on whether their patient record contained International Classification of Disease (ICD)-9 or ICD-10 codes for homelessness/inadequate housing. Main Outcome Measures: One-year rates of reoperation for amputation, irrigation and debridement, repeat ORIF, repair of nonunion/malunion, and implant removal in isolation. Results: Homeless patients had significantly higher odds of undergoing amputation (adjusted odds ratio [aOR] 1.59, 95% confidence interval [CI] 1.08-2.27, P = 0.014), irrigation and debridement (aOR 1.22, 95% CI 1.08-1.37, P < 0.001), and repeat ORIF (aOR 1.16, 95% CI 1.00-1.35, P = 0.045). Implant removal was less common in homeless patients (aOR 0.65, 95% CI 0.59-0.72, P < 0.001). There was no significant difference between homeless and nonhomeless patients in the rate of nonunion/malunion repair (aOR 0.87, 95% CI 0.63-1.18, P = 0.41). Conclusions: Homelessness is a significant risk factor for worse surgical outcomes following ankle fracture surgery. The findings of this study warrant future research to identify gaps in surgical fracture care for patients with housing insecurity and underscore the importance of developing interventions to advance health equity for this vulnerable patient population. Level of Evidence: Prognostic Level III.
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This study was performed to aid the management of the fishery for Antarctic krill Euphausia superba. Krill are an important component of the Antarctic marine ecosystem, providing a key food source for many marine predators. Additionally, krill are the target of the largest commercial fishery in the Southern Ocean, for which annual catches have been increasing and concentrating in recent years. The krill fishery is managed by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), which has endorsed a new management framework that requires information about the spatial distribution and biomass of krill. Here, we use krill density estimates from acoustic surveys and a GAMM framework to model habitat properties associated with high krill biomass during summer and winter in the northern Antarctic Peninsula region, an area important to the commercial fishery. Our models show elevated krill density associated with the shelf break, increased sea surface temperature, moderate chlorophyll-a concentration and increased salinity. During winter, our models show associations with shallow waters (< 1500 m) with low sea-ice concentration, medium sea-level anomaly and medium current speed. Our models predict temporal averages of the distribution and density of krill, which can be used to aid CCAMLR's revised ecosystem approach to fisheries management. Our models have the potential to help in the spatial and temporal design of future acoustic surveys that would preclude the need for modelled extrapolations. We highlight that the ecosystem approach to fisheries management of krill critically depends upon such field observations at relevant spatial and temporal scales. Supplementary Information: The online version contains supplementary material available at 10.1007/s00300-022-03039-y.
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Antarctic krill play an important role in biogeochemical cycles and can potentially generate high-particulate organic carbon (POC) fluxes to the deep ocean. They also have an unusual trait of moulting continuously throughout their life-cycle. We determine the krill seasonal contribution to POC flux in terms of faecal pellets (FP), exuviae and carcasses from sediment trap samples collected in the Southern Ocean. We found that krill moulting generated an exuviae flux of similar order to that of FP, together accounting for 87% of an annual POC flux (22.8 g m-2 y-1). Using an inverse modelling approach, we determined the krill population size necessary to generate this flux peaked at 261 g m-2. This study shows the important role of krill exuviae as a vector for POC flux. Since krill moulting cycle depends on temperature, our results highlight the sensitivity of POC flux to rapid regional environmental change.
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Ciclo del Carbono , Carbono/metabolismo , Euphausiacea/fisiología , Muda/fisiología , Animales , Biomasa , Geografía , Sedimentos Geológicos/química , Océanos y Mares , Material Particulado/análisis , Dinámica Poblacional , Estaciones del AñoRESUMEN
BACKGROUND: Childhood asthma is a common condition. Currently there is no validated objective test which can be used to guide asthma treatment in children. This study tests the hypothesis that the addition of fractional exhaled nitric oxide (FENO) monitoring in addition to standard care reduces the number of exacerbations (or attacks) in children with asthma. METHODS: This is a multi-centre, randomised controlled study. Children will be included of age 6-16 years who have a diagnosis of asthma, currently use inhaled corticosteroids (ICSs) and have had an exacerbation in the previous 12 months. Exclusion criteria include being unable to provide FENO measurement at baseline assessment, having another chronic respiratory condition and being currently treated with maintenance oral steroids. Participants will be recruited in both primary and secondary care settings and will be randomised to either receive asthma treatment guided by FENO plus symptoms (FENO group) or asthma treatment guided by symptoms only (standard care group). Within the FENO group, different treatment decisions will be made dependent on changes in FENO. Participants will attend assessments 3, 6, 9 and 12 months post randomisation. The primary outcome is asthma exacerbation requiring prescription and/or use of an oral corticosteroid over 12 months as recorded by the participant/parent or in general practitioner records. Secondary outcomes include time to first attack, number of attacks, asthma control score and quality of life. Adherence to ICS treatment is objectively measured by an electronic logging device. Participants are invited to participate in a "phenotyping" assessment where skin prick reactivity and bronchodilator response are determined and a saliva sample is collected for DNA extraction. Qualitative interviews will be held with participants and research nurses. A health economic evaluation will take place. DISCUSSION: This study will evaluate whether FENO can provide an objective index to guide and stratify asthma treatment in children. TRIAL REGISTRATION: ISRCTN, ISRCTN67875351. Registered on 12 April 2017. Prospectively registered.
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Asma/diagnóstico , Pruebas Respiratorias , Óxido Nítrico/metabolismo , Administración por Inhalación , Adolescente , Corticoesteroides/administración & dosificación , Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Asma/metabolismo , Asma/fisiopatología , Biomarcadores/metabolismo , Niño , Progresión de la Enfermedad , Espiración , Femenino , Humanos , Masculino , Estudios Multicéntricos como Asunto , Valor Predictivo de las Pruebas , Ensayos Clínicos Controlados Aleatorios como Asunto , Reino UnidoRESUMEN
We simulate a densely jammed, athermal assembly of repulsive soft particles immersed in a solvent. Starting from an initial condition corresponding to a quench from a high temperature, we find nontrivial slow dynamics driven by a gradual release of stored elastic energy, with the root mean squared particle speed decaying as a power law in time with a fractional exponent. This decay is accompanied by the presence within the assembly of spatially localized and temporally intermittent "hot spots" of nonaffine deformation, connected by long-ranged swirls in the velocity field, reminiscent of the local plastic events and long-ranged elastic propagation that have been intensively studied in sheared amorphous materials. The pattern of hot spots progressively coarsens, with the hot-spot size and separation slowly growing over time, and the associated correlation length in particle speed increasing as a sublinear power law. Each individual spot, however, exists only transiently within an overall picture of strongly intermittent dynamics.
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Overweight and obesity may increase risk of disease progression in men with prostate cancer, but there have been few studies of weight loss interventions in this patient group. In this study overweight or obese men treated for prostate cancer were randomised to a self-help diet and activity intervention with telephone-based dietitian support or a wait-list mini-intervention group. The intervention group had an initial group meeting, a supporting letter from their urological consultant, three telephone dietitian consultations at 4-week intervals, a pedometer and access to web-based diet and physical activity resources. At 12 weeks, men in both groups were given digital scales for providing follow-up weight measurements, and the wait-list group received a mini-intervention of the supporting letter, a pedometer and access to the web-based resources. Sixty-two men were randomised; fifty-four completed baseline and 12-week measurements, and fifty-one and twenty-seven provided measurements at 6 and 12 months, respectively. In a repeated-measures model, mean difference in weight change between groups (wait-list mini-intervention minus intervention) at 12 weeks was -2·13 (95 % CI -3·44, -0·82) kg (P = 0·002). At 12 months the corresponding value was -2·43 (95 % CI -4·50, -0·37) kg (P = 0·022). Mean difference in global quality of life score change between groups at 12 weeks was 12·3 (95 % CI 4·93, 19·7) (P = 0·002); at 12 months there were no significant differences between groups. Results suggest the potential of self-help diet and physical activity intervention with trained support for modest but sustained weight loss in this patient group.
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Dieta , Ejercicio Físico , Neoplasias de la Próstata/fisiopatología , Autoeficacia , Pérdida de Peso , Índice de Masa Corporal , Humanos , Masculino , Persona de Mediana Edad , Obesidad/terapia , Proyectos Piloto , Calidad de VidaRESUMEN
The efficiency of deep-ocean CO2 sequestration is regulated by the relative balance between inorganic and organic carbon export respectively acting through the biological carbon pump (BCP) and the carbonate counter pump (CCP). The composition and abundance of calcifying species in the prevailing oceanic plankton community plays a major role in driving the CCP. Here we assess the role of these calcifying organisms in regulating the strength of the CCP in a Southern Ocean region (northern Scotia Sea) known to be a major hotspot for the drawdown of atmospheric CO2. We show that, when shelled pteropods dominate the calcifying community, the total annual reduction of CO2 transferred to the deep ocean doubles (17%) compared to when other plankton calcifiers dominate (3-9%). Furthermore, predation enhances their contribution through the removal of organic soft tissue. Pteropods are threatened in polar regions by ocean warming and acidification. We determine that their potential decline would have major implications to the comparative strengths of the BCP and CCP.
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Carbonatos/análisis , Especies en Peligro de Extinción , Océanos y Mares , Carbono/análisis , Compuestos Orgánicos/análisis , Material Particulado/análisis , Plancton/metabolismo , Estaciones del AñoRESUMEN
It has recently been argued that steady-state vorticity bands cannot arise in shear thickening suspensions because the normal stress imbalance across the interface between the bands will set up particle migrations. In this Letter, we develop a simple continuum model that couples shear thickening to particle migration. We show by linear stability analysis that homogeneous flow is unstable towards vorticity banding, as expected, in the regime of negative constitutive slope. In full nonlinear computations, we show, however, that the resulting vorticity bands are unsteady, with spatiotemporal patterns governed by stress-concentration coupling. We furthermore show that these dynamical bands also arise in direct particle simulations, in good agreement with the continuum model.
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OBJECTIVE: To establish the long term outcomes of risk stratified management of differentiated thyroid cancer (DTC). BACKGROUND: Guidelines for management of DTC lack a strong evidence base and expose patients to overtreatment. This prospective study of patients diagnosed with DTC between 1977 and 2012 describes the long term outcomes of a conservative risk stratified (AMES) management policy. METHODS: Outcomes were analysed around patient and tumour characteristics, primary intervention (surgery ± radioiodine (RAI)), in terms of mortality, recurrence and reintervention. RESULTS: Median follow-up in 348 patients was 14 years: mean age 48 (range 10-91) years, 257 (73.9%) female, 222 (68.3%) papillary cancer, tumour size 3.4 ± 2.0 cm (mean ± SD). 89 (25.6%) AMES high risk, 116 (33.3%) TNM stage III/IV and 16 (4.6%) had distant metastases. Primary surgery comprised lobectomy in 189 (54.3%): 11 (5.8%) patients had subsequent completion total thyroidectomy with cancer present in five. Primary nodal surgery was performed in 142 (40.8%) patients. 35 (13.5%) low and 43 (48.3%) high risk patients received RAI following initial surgery. Overall disease specific survival (DSS) was 92.1% at 10 years and 90.7% at 20 years. DSS at 20 years was 99.2% in low risk cases. AMES risk scoring predicted both survival and recurrence. Patients receiving RAI and AMES high risk were significantly associated with increased risk of death and recurrence. CONCLUSIONS: Routine total thyroidectomy and RAI are not justifiable for low risk DTC. Treatment should be tailored to risk and AMES risk stratification remains a simple reliable clinical tool.
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Adenocarcinoma/terapia , Neoplasias de la Tiroides/terapia , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Niño , Femenino , Humanos , Radioisótopos de Yodo/administración & dosificación , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Medición de Riesgo , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/cirugía , Tiroidectomía , Adulto JovenRESUMEN
The current study examined the relationship between vitamin D status and muscle strength in young healthy adults: residents (>6 months) and newcomers (0-3 months), originally from sunny climate countries but currently living in the northeast of Scotland. Our longitudinal data found a positive, albeit small, relationship between vitamin D status and knee extensor isometric strength. INTRODUCTION: Vitamin D has been suggested to play a role in muscle health and function, but studies so far have been primarily in older populations for falls prevention and subsequent risk of fractures. METHODS: Vitamin D status was assessed in a healthy young adults from sunny climate countries (n = 71, aged 19-42 years) with 56% seen within 3 months of arriving in Aberdeen [newcomers; median (range) time living in the UK = 2 months (9-105 days)] and the remainder resident for >6 months [residents; 23 months (6-121 months)]. Participants attended visits every 3 months for 15 months. At each visit, fasted blood samples were collected for analysis of serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type I collagen (P1NP). Maximal voluntary contractions (MVC) were performed for grip strength (both arms) and for maximal isometric strength of the knee extensors (right knee). RESULTS: There were small seasonal variations in 25(OH)D concentrations within the newcomers and residents, but no seasonal variation in bone turnover markers. There was a positive, albeit small, association between 25(OH)D and knee extensor maximal isometric strength. Mixed modelling predicted that for each 1 nmol/L increase in 25(OH)D, peak torque would increase by 1 Nm (p = 0.04). CONCLUSIONS: This study suggests that vitamin D may be important for muscle health in young adults migrating from sunnier climates to high latitudes, yet the potential effect is small.
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Clima , Emigrantes e Inmigrantes , Fuerza Muscular/fisiología , Vitamina D/análogos & derivados , Adulto , Recolección de Muestras de Sangre/métodos , Femenino , Fuerza de la Mano/fisiología , Humanos , Articulación de la Rodilla/fisiología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Escocia , Estaciones del Año , Pigmentación de la Piel/fisiología , Luz Solar , Vitamina D/sangre , Adulto JovenRESUMEN
Antarctic krill (Euphausia superba) play a central role in the food web of the Southern Ocean, forming a link between primary production and large predators. Krill produce large, faecal pellets (FP) which can form a large component of mesopelagic particulate organic carbon (POC) fluxes. However, the patchy distribution of krill swarms, highly variable pellet composition, and variable sinking and attenuation rates means that these episodic, but potentially large, carbon fluxes are difficult to sample or model. We measured particle flux and type using Marine Snow Catchers (MSC) in the marginal ice zone near the South Orkneys, Antarctica. Krill FP were the dominant component of the POC flux in the upper 200 m (typically 60-85%). FP sinking velocities measured onboard were highly variable (15-507 m d-1) but overall high, with mean equivalent velocities of 172, 267, and 161 m d-1 at our three stations. The high numbers of krill FP sinking through the mesopelagic suggest that krill FP can be transferred efficiently and/or that rates of krill FP production are high. We compared our direct MSC-derived estimates of krill FP POC flux (33-154 mg C m-2 d-1) and attenuation to estimates of krill FP production based on previous measurements of krill density and literature FP egestion rates, and estimated net krill FP attenuation rates in the upper mesopelagic. Calculated attenuation rates are sensitive to krill densities in the overlying water column but suggest that krill FP could be transferred efficiently through the upper mesopelagic, and, in agreement with our MSC attenuation estimates, could make large contributions to bathypelagic POC fluxes. Our study contrasts with some others which suggest rapid FP attenuation, highlighting the need for further work to constrain attenuation rates and assess how important the contribution of Antarctic krill FP could be to the Southern Ocean biological carbon pump.
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OBJECTIVE: To compare psychosocial outcomes (follow-up related worries and satisfaction with follow-up related information and support) over 30 months of two alternative management policies for women with low-grade abnormal cervical cytology. METHODS: Women aged 20-59 years with low-grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. RESULTS: On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI -3.6 to -1.3) lower for follow-up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow-up related satisfaction with information and support (-2.4; -3.3 to -1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th- and 18th-month time points. These differences remained when the analysis was stratified by post-school education. CONCLUSIONS: Women with low-grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.
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Ansiedad/psicología , Colposcopía/psicología , Citodiagnóstico/psicología , Displasia del Cuello del Útero/psicología , Neoplasias del Cuello Uterino/psicología , Adulto , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Morbilidad , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/patología , Adulto Joven , Displasia del Cuello del Útero/patologíaRESUMEN
PURPOSE: Missing data are a major problem in the analysis of data from randomised trials affecting power and potentially producing biased treatment effects. Specifically focussing on quality of life outcomes, we aimed to report the amount of missing data, whether imputation was used and what methods and was the missing mechanism discussed from four leading medical journals and compare the picture to our previous review nearly a decade ago. METHODS: A random selection (50 %) of all RCTS published during 2013-2014 in BMJ, JAMA, Lancet and NEJM was obtained. RCTs reported in research letters, cluster RCTs, non-randomised designs, review articles and meta-analysis were excluded. RESULTS: We included 87 RCTs in the review of which 35 % the amount of missing primary QoL data was unclear, 31 (36 %) used imputation. Only 23 % discussed the missing data mechanism. Nearly half used complete case analysis. Reporting was more unclear for secondary QoL outcomes. Compared to the previous review, multiple imputation was used more prominently but mainly in sensitivity analysis. CONCLUSIONS: Inadequate reporting and handling of missing QoL data in RCTs are still an issue. There is a large gap between statistical methods research relating to missing data and the use of the methods in applications. A sensitivity analysis should be undertaken to explore the sensitivity of the main results to different missing data assumptions. Medical journals can help to improve the situation by requiring higher standards of reporting and analytical methods to deal with missing data, and by issuing guidance to authors on expected standard.
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Recolección de Datos/métodos , Calidad de Vida/psicología , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The best data on prognosis comes from population-based incident cohorts but few such cohorts exist for Parkinson's disease and atypical parkinsonism. METHODS: The PINE study is a prospective follow-up study of an incident cohort of people with degenerative or vascular parkinsonism and age-sex matched controls. Participants have annual follow-up from diagnosis until death with review of primary/secondary care records and linkage to the UK death register. Data are collected on survival, disability (dependency on others for activities of daily living) and institutionalization. Research criteria are used to guide the clinical diagnosis, which is updated annually. We compared all-cause mortality, disability and institutionalization in patients (subdivided by diagnosis) and controls, adjusted for important confounders. RESULTS: 323 incident parkinsonian patients (199 Parkinson's disease, 124 atypical parkinsonism, mean age at diagnosis 75yrs) and 262 controls (mean age 75yrs) had 1349 and 1334 person-years follow-up respectively (maximum follow-up 10 years). All outcomes were worse in parkinsonian patients than controls, especially in atypical parkinsonism (adjusted mortality hazards ratios Parkinson's disease 2.49, 95%CI 1.72-3.58, atypical parkinsonism, 6.85, 95%CI 4.78-9.81). Median survival times for Parkinson's disease and atypical parkinsonism were 7.8 and 2.7 years respectively but were very age-dependent. At three years the rates of death or dependency were controls 21%, Parkinson's disease 46%, atypical parkinsonism 96% whilst overall institutionalization rates were 5%, 15% and 55% respectively. CONCLUSION: The prognosis of Parkinson's disease and atypical parkinsonism in this unselected incident cohort was significantly worse than previously reported. This has important implications for patient management.
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Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/epidemiología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neuroimagen , Trastornos Parkinsonianos/mortalidad , PronósticoRESUMEN
OBJECTIVES: Late HIV diagnosis is associated with increased morbidity and mortality, increased risk of transmission, impaired response to antiretroviral therapy and increased health care costs. The aim of this study was to determine the factors associated with late HIV diagnosis in Grampian, North-East Scotland. STUDY DESIGN: A population based retrospective database analysis. METHODS: All newly diagnosed HIV positive individuals in Grampian, North-East Scotland between 2009 and 2014 were included in the study. Participants were classified as having a late diagnosis if the CD4 cell count at presentation was less than 350 cells/mm3. Socio-economic and demographic factors were investigated in relation to outcome (late diagnosis) using Chi-squared and Mann-Whitney tests. RESULTS: CD4 cell count results were available for 111 (89.5%) of the 124 newly diagnosed individuals during the study period. The prevalence of late diagnosis was 53.2% (n = 59). Those infected via heterosexual mode of transmission had a 2.83 times higher odds of late diagnosis (OR 2.83 [95% CI: 1.10-7.32]) than men who have sex with men (MSM) and those with no previous HIV testing had a 5.46 increased odds of late diagnosis (OR 5.46 [95% CI: 1.89-15.81]) compared to those who had previously been tested. Missed opportunities for HIV diagnosis were identified in 16.3% (n = 15) of participants. CONCLUSION: Heterosexual individuals and those with no previous HIV testing were more likely to be diagnosed late. Targeted initiatives to increase perception of HIV risk and uptake of testing in these risk groups are recommended.
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Diagnóstico Tardío/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Adolescente , Adulto , Recuento de Linfocito CD4/estadística & datos numéricos , Femenino , Heterosexualidad/estadística & datos numéricos , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Escocia , Adulto JovenRESUMEN
We consider a continuum model of active viscoelastic matter, whereby an active nematic liquid crystal is coupled to a minimal model of polymer dynamics with a viscoelastic relaxation time τ(C). To explore the resulting interplay between active and polymeric dynamics, we first generalize a linear stability analysis (from earlier studies without polymer) to derive criteria for the onset of spontaneous heterogeneous flows (strain rate) and/or deformations (strain). We find two modes of instability. The first is a viscous mode, associated with strain rate perturbations. It dominates for relatively small values of τ(C) and is a simple generalization of the instability known previously without polymer. The second is an elastomeric mode, associated with strain perturbations, which dominates at large τ(C) and persists even as τ(C)â∞. We explore the dynamical states to which these instabilities lead by means of direct numerical simulations. These reveal oscillatory shear-banded states in one dimension and activity-driven turbulence in two dimensions even in the elastomeric limit τ(C)â∞. Adding polymer can also have calming effects, increasing the net throughput of spontaneous flow along a channel in a type of drag reduction. The effect of including strong antagonistic coupling between the nematic and polymer is examined numerically, revealing a rich array of spontaneously flowing states.
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BACKGROUND: A key skill for a practising clinician is being able to do research, understand the statistical analyses and interpret results in the medical literature. Basic statistics has become essential within medical education, but when, what and in which format is uncertain. METHODS: To inform curriculum design/development we undertook a quantitative survey of fifth year medical students and followed them up with a series of focus groups to obtain their opinions as to what statistics teaching they want, when and how. RESULTS: A total of 145 students undertook the survey and five focus groups were held with between 3 and 9 participants each. Previous statistical training varied and students recognised their knowledge was inadequate and keen to see additional training implemented. Students were aware of the importance of statistics to their future careers, but apprehensive about learning. Face-to-face teaching supported by online resources was popular. Focus groups indicated the need for statistical training early in their degree and highlighted their lack of confidence and inconsistencies in support. CONCLUSION: The study found that the students see the importance of statistics training in the medical curriculum but that timing and mode of delivery are key. The findings have informed the design of a new course to be implemented in the third undergraduate year. Teaching will be based around published studies aiming to equip students with the basics required with additional resources available through a virtual learning environment.
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Curriculum , Educación de Pregrado en Medicina/normas , Investigación/educación , Estadística como Asunto/educación , Estudiantes de Medicina , Actitud del Personal de Salud , Docentes Médicos , Grupos Focales , Humanos , Escocia , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios , EnseñanzaRESUMEN
A paradigm for internally driven matter is the active nematic liquid crystal, whereby the equations of a conventional nematic are supplemented by a minimal active stress that violates time-reversal symmetry. In practice, active fluids may have not only liquid-crystalline but also viscoelastic polymer degrees of freedom. Here we explore the resulting interplay by coupling an active nematic to a minimal model of polymer rheology. We find that adding a polymer can greatly increase the complexity of spontaneous flow, but can also have calming effects, thereby increasing the net throughput of spontaneous flow along a pipe (a "drag-reduction" effect). Remarkably, active turbulence can also arise after switching on activity in a sufficiently soft elastomeric solid.