Long-term mortality after internal fixation of calcaneal fractures: a retrospective study.

The aim of this study was to describe the mortality risk after calcaneal fractures which required internal fixation and evaluate predictors of survival. During the observed 11-year period (1995-2006), 178 consecutive patients underwent operative fixation for displaced intra-articular calcaneal fractures. Patient demographics, mechanism of injury, and social deprivation (Carstairs index) were recorded. Mortality was obtained from patient notes. Causes of mortality were obtained from the national database. Standardised mortality ratios (SMRs) were calculated. Ten patients were lost to follow-up. Of the remaining 168 patients, the mean age was 41 (range 14-77) years. Females [n = 33, 46.3 standard deviation (SD) 17.1 years] were significantly (difference 6.5 years, 95% CI 1.1-11.9, p = 0.02) older than male patients (n = 135, 39.8 SD 13.4 years). During the study period, 28 patients died. The overall unadjusted survival rate was 92.8% (95% CI 87.0-98.7) at 10 years and 81.9% (95% CI 76.2-87.6) at 15 years. The SMR at 10 years was 5.2 (95% CI 2.8-13.3) for males and 1.4 (95% CI - 4.9 to 7.8) for females. Cox regression analysis demonstrated male gender to be a significant predictor of mortality (hazard ratio 2.77, 95% 3.83-9.65, p = 0.01) adjusted for age and social deprivation. Male patients requiring internal fixation of intra-articular calcaneal fractures have a significantly increased mortality risk compared to an age- and gender-matched population. Further study is warranted to fully identify the reasons behind this, which may enable their survival to be improved.Level of evidence Retrospective Cohort study, Level 4.

The cerebral angiome: High resolution MicroCT imaging of the whole brain cerebrovasculature in female and male mice.

The cerebrovascular system provides crucial functions that maintain metabolic and homeostatic states of the brain. Despite its integral role of supporting cerebral viability, the topological organization of these networks remains largely uncharacterized. This void in our knowledge surmises entirely from current technological limitations that prevent the capturing of data through the entire depth of the brain. We report high-resolution reconstruction and analysis of the complete vascular network of the entire brain at the capillary level in adult female and male mice using a vascular corrosion cast procedure. Vascular network analysis of the whole brain revealed sex-related differences of vessel hierarchy. In addition, region-specific network analysis demonstrated different patterns of angioarchitecture between brain subregions and sex. Furthermore, our group is the first to provide a three-dimensional analysis of the angioarchitecture and network organization in a single reconstructed tomographic data set that encompasses all hierarchy of vessels in the brain of the adult mouse.

Patients with laboratory evidence of West Nile virus disease without reported fever.

In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013.

Incremental health care services and expenditures associated with depression among individuals with cutaneous lupus erythematosus (CLE).

Objectives The objective of this paper is to describe the annual direct medical expenditures for cutaneous lupus erythematosus (CLE) patients, and to estimate the incremental health care expenditures and utilization associated with depression among adults with CLE, while controlling for covariates. Methods Using the 2014 Medical Expenditure Panel Survey (MEPS), we compared CLE patients with and without depression to determine differences in: (a) health care utilization-inpatient, outpatient, office-based and emergency room (ER) visits, and prescriptions filled; and (b) expenditures-total costs, inpatient, outpatient, office-based, ER, and prescription medication costs, and other costs using demography-adjusted and comorbidity-adjusted multivariate models (age, gender, race/ethnicity, marital status, education, perception of health status, poverty category, smoking status, and Charlson Comorbidity Index). Results The total direct medical expenditure associated with CLE is estimated at approximately $29.7 billion in 2014 US dollars. After adjusting for covariates, adults with CLE and depression had more hospital discharges (utilization ratio (UR) = 1.13, 95% confidence interval (CI) (1.00-1.28)), ER visits (UR = 1.17, 95% CI (1.09-1.37)), and prescribed medicines (UR = 2.15, 95% CI (1.51-3.05)) than those without depression. Adults with CLE and depression had significantly higher average annual total expenditure that those without depression ($19,854 vs. $9735). Conclusions High health care expenditures are significant for patients with CLE, especially among those with depression. Prescription drugs, inpatient visits, and ER visits contributed most to the total expenditures in CLE patients with depression. Early diagnosis and treatment of depression in CLE patients may reduce total health care expenditures and utilization in this population.

High mortality in younger patients with major osteoporotic fractures.

Data were gathered with regard to mortality after fractures in 1006 younger patients. Results revealed that major osteoporotic fractures of the hip and humerus and drinking alcohol to excess were related to an increased risk of mortality. INTRODUCTION: Major osteoporotic fractures are known to be associated with increased mortality in older individuals. It is less clear whether this also applies to younger patients. METHODS: Date were gathered regarding patient demographics, fracture pattern, mechanism of injury, as well as smoking and alcohol intake at the time of injury in consecutive patients aged between 40 and 55 who presented to a UK trauma centre over a 12-month period. Mortality data was taken from the electronic patient records and was cross referenced with data from the General Registrar Office of Scotland. Cox regression analysis was used to identify independent predictors of mortality after adjusting for confounding factors. RESULTS: The study cohort consisted of 1006 patients, of which 53% were male. The commonest mechanism of injury was a fall. We obtained complete data regarding mortality for all patients at a median of 5.4 years (inter-quartile range 5.1 to 5.6). During this period, 46 patients were identified as being deceased. The overall standardised mortality ratio for the cohort was substantially increased relative to the age and sex matched general population with a ratio of 3.89 (95% confidence intervals (CI) 1.59 to 6.19). Alcohol excess and fractures involving the humerus and the neck of femur were independent predictors of mortality. CONCLUSIONS: Young individuals with hip and humerus fractures have a significantly increased mortality risk after their injury relative to the general population. The results of our study suggest that this may be in part due to a high prevalence of alcohol excess.

Does socioeconomic status influence the epidemiology and outcome of distal radial fractures in adults?

PURPOSE: The aim of this study in adult patients with a distal radial fracture was to determine whether socioeconomic status influenced the epidemiology, mechanism of injury, fracture severity, or the outcome according to function, radiographic assessment, and rate of associated complications. METHODS: We identified 3983 distal radial fractures over a 7-year period. Socioeconomic status was assigned using the Carstairs score, and the population was divided into quintiles depending on deprivation. Patient demographics, mechanism of injury, fracture severity, and radiographic assessment at time of injury were assessed for epidemiological differences according to social quintile. Functional outcome was assessed using grip strength, Moberg pickup test, return to normal use of the hand, and range of movement. Radiographs were assessed at 1 week, 6 weeks, and 1 year. Complications were defined as malunion, carpal tunnel syndrome, complex regional pain syndrome (CRPS), persistent pain, and subjective cosmetic deformity of the wrist. RESULTS: Socioeconomically deprived patients were significantly younger (p < 0.001) and more likely to be male (p = 0.017); after adjusting for confounding factors, deprived patients were 3.1 (95% CI 1.4-4.7) years younger than the most affluent patients (p < 0.001). Deprived patients were more likely to sustain their fracture by a high-energy mechanism (p = 0.004). There were no significant differences between quintiles in outcome. There was a significantly greater prevalence of CRPS in more affluent patients (p = 0.004). CONCLUSIONS: Socioeconomically deprived patients sustaining a distal radial fracture are more likely to be younger and male. Outcome is not influenced by socioeconomic status, but the prevalence of CRPS is greater in more affluent patients.

Social deprivation influences the epidemiology and outcome of proximal humeral fractures in adults for a defined urban population of Scotland.

We present the epidemiology and incidence of proximal humeral fractures over a 17-year period for a defined urban population that represents approximately 13% of the population in Scotland, and functional outcome in relation to the socio-economic status of the patient. The incidence of proximal humeral fractures significantly increased during the study period from 47.9/10(5)/year to 98.7/10(5)/year in 2008 (p < 0.0001), which was greatest for the most socially deprived patients reaching 274.2/10(5)/year in 2008 (p < 0.0001). The most deprived patients sustained their fracture 4 years earlier than the most affluent patients (p = 0.026). Social deprivation was an independent predictor, after adjusting for other confounding variables using multivariable regression analysis, of a significantly worse functional outcome according to the Constant score at 1 year (p = 0.046). Preventative measures, especially for the most socially deprived patients within society, need to be instigated urgently to address the increasing incidence of proximal humeral fractures and alleviate the burden of these morbid fractures in the future. Whether the observed increased incidence is generalisable to a national population would need to be confirmed in future studies.

Photosymbiosis reduces the environmental stress response under a heat challenge in a facultatively symbiotic coral.

The symbiosis between corals and dinoflagellates of the family Symbiodiniaceae is sensitive to environmental stress. The oxidative bleaching hypothesis posits that extreme temperatures lead to accumulation of photobiont-derived reactive oxygen species ROS, which exacerbates the coral environmental stress response (ESR). To understand how photosymbiosis modulates coral ESRs, these responses must be explored in hosts in and out of symbiosis. We leveraged the facultatively symbiotic coral Astrangia poculata, which offers an opportunity to uncouple the ESR across its two symbiotic phenotypes (brown, white). Colonies of both symbiotic phenotypes were exposed to three temperature treatments for 15 days: (i) control (static 18 °C), (ii) heat challenge (increasing from 18 to 30 °C), and (iii) cold challenge (decreasing from 18 to 4 °C) after which host gene expression was profiled. Cold challenged corals elicited widespread differential expression, however, there were no differences between symbiotic phenotypes. In contrast, brown colonies exhibited greater gene expression plasticity under heat challenge, including enrichment of cell cycle pathways involved in controlling photobiont growth. While this plasticity was greater, the genes driving this plasticity were not associated with an amplified environmental stress response (ESR) and instead showed patterns of a dampened ESR under heat challenge. This provides nuance to the oxidative bleaching hypothesis and suggests that, at least during the early onset of bleaching, photobionts reduce the host's ESR under elevated temperatures in A. poculata.

Leukaemias into the 21st century. Part 2: the chronic leukaemias.

Like the acute leukaemias, the chronic leukaemias are broadly classified according to their cell lineage of origin. Chronic myeloid leukaemia and chronic lymphocytic leukaemia are the most common disease entities within the myeloid and lymphoid lineages, although several less common entities are well recognised within each broad subgroup. In common with the dramatic progress in the acute leukaemias, there has been considerable progress in our understanding of the biology and molecular genetics of the chronic leukaemias that is now being translated into significant therapeutic advances.

Undisplaced intracapsular hip fractures in the elderly: predicting fixation failure and mortality. A prospective study of 162 patients.

BACKGROUND: Reported revision of internal fixation for undisplaced intracapsular hip fractures is between 12 and 17% at 1 year. This risk is greater for elderly patients, for whom mortality after such a fracture is also higher. Our purpose was to identify predictors of fixation failure and mortality for elderly patients sustaining undisplaced intracapsular hip fractures, and to assess whether their socioeconomic status affected their outcome. METHODS: During a 3-year period we prospectively compiled a consecutive series of 162 elderly (≥65 years old) patients who underwent internal fixation for an undisplaced (Garden stage I or II) intracapsular hip fracture. Patient demographics, American Society of Anesthesiologists (ASA) grade, and posterior tilt (measured on the lateral radiograph) were recorded pre-operatively. All patients were followed up for a minimum of 1 year. Each patient's socioeconomic status was assigned by use of the Scottish Index of Multiple Deprivation. Patient mortality was established by use of the General Register Office for Scotland. RESULTS: There were 28 failures of fixation during the study period. In Cox regression analysis, ASA grade and the presence of posterior tilt (p < 0.0001) were significant independent predictors of fixation failure. Overall unadjusted mortality at 1 year was 19% (n = 30/162). Cox regression analysis also affirmed ASA grade to be the only significant independent predictor of 1-year mortality (p = 0.003). The standardised mortality rate for the cohort was 2.3 (p < 0.001), and was significantly greater for patients less than 80 years of age (p = 0.004). Socioeconomic status did not affect outcome, but the most deprived patients sustain their fracture at a significantly younger age (p = 0.001). CONCLUSION: We have demonstrated that ASA grade and posterior tilt of the femoral neck are independent predictors of fixation failure of undisplaced intracapsular hip fractures in elderly patients, and ASA grade was also an independent predictor of mortality.

Leukaemias into the 21st century: part 1: the acute leukaemias.

The leukaemias are a biologically and clinically heterogeneous group of malignancies, which manifest as clonal expansions of a single cell at different stages of lympho-haemopoietic development. The transformed cell acquires an unrestrained capacity for self-renewal and, in the case of the acute leukaemias, also fails to differentiate into functional mature cells. Historically leukaemias were classified using a combination of clinical and (presumed) cell lineage criteria. Thus, the four major subgroups of acute and chronic myeloid leukaemia and acute and chronic lymphoid leukaemia were recognised. Up until the last 10-15 years, patients within each major subgroup were treated along broadly similar lines. Genetic abnormalities have been recognised in certain leukaemias for over 50 years; however, the recent explosion in our understanding of the frequency and complexity of molecular abnormalities in the leukaemias has 'opened the door' for the design of more targeted therapies with the expectation that their incorporation into therapeutic regimens will be associated with greater efficacy and less off-target toxicity.

The relationship of fall-related fractures to social deprivation.

UNLABELLED: The relationship between fall-related fractures and social deprivation was studied in 3,843 patients. The incidence of fractures correlated with deprivation in all age groups although the spectrum of fractures was not affected by deprivation. The average age and the prevalence of hip fractures decreased with increasing deprivation. INTRODUCTION: This study examines the relationship between social deprivation and fall-related fractures. Social deprivation has been shown to be a predisposing factor in a number of diseases. There is evidence that it is implicated in fractures in children and young adults, but the evidence that it is associated with fragility fractures in older adults is weak. As fragility fractures are becoming progressively more common and increasingly expensive to treat, the association between social deprivation and fractures is important to define. METHODS: All out-patient and in-patient fractures presenting to the Royal Infirmary of Edinburgh over a 1-year period were prospectively recorded. The fractures caused by falls from a standing height were analysed in all patients of at least 15 years of age. Social deprivation was assessed using the Carstairs score and social deprivation deciles, and the 2001 census was used to calculate fracture incidence. The data were used to analyse the relationship between social deprivation and fall-related fractures in all age groups. RESULTS: The incidence of fall-related fractures correlated with social deprivation in all age groups including fragility fractures in the elderly. The overall spectrum of fractures was not affected by social deprivation although the prevalence of proximal femoral fractures decreased with increasing deprivation. The average age of patients with fall-related fractures also decreased with increasing social deprivation as did the requirement for in-patient treatment. CONCLUSIONS: This is the first study to show the relationship between fall-related fractures and social deprivation in older patients. We believe that the decreased incidence of proximal femoral fractures, and the lower average age of patients with fall-related fractures, in the socially deprived relates to the relative life expectancies in the different deprivation deciles.

Evaluation of the immunoregulatory activity of intraepithelial lymphocytes in a mouse model of chronic intestinal inflammation.

Intraepithelial lymphocytes (IELs) represent the first line of lymphocyte defense against the intestinal bacteria. Although previous studies have demonstrated a protective role of IELs in the development of colitis, the data supporting a regulatory role for IELs are limited. The objective of this study was to examine the suppressive activity of IELs in vitro and in vivo using a mouse model of chronic small and large bowel inflammation. Adoptive transfer of CD8α(+) IELs isolated from small intestines of wild-type (WT) mice into TCR ßxδ-deficient (TCR ßxδ(-/-)) recipients did not prevent or delay the onset of the disease induced by WT CD4(+)CD45RB(high) T cells. On the contrary, we observed a more rapid onset of wasting and clinical signs of intestinal inflammation when compared with animals injected with CD4(+)CD45RB(high) T cells alone. Histopathological scores of small and large bowel did not differ significantly between the two groups. Transfer of IELs alone did not produce any pathological changes. Real-time PCR analysis of intestinal tissues showed up-regulation of message for T(h)1- and macrophage-derived cytokines in colon and small bowel. Using Foxp3-GFP reporter mice, we were unable to detect any Foxp3(+) cells within the CD8α(+) IELs but did find a small population of Foxp3(+)CD4(+) IELs in the small and large bowel. Using in vitro suppression assay, we found that neither TCRαß(+)CD8αα(+), TCRαß(+)CD8αß(+) nor TCRγδ(+)CD8αα(+) IELs were capable of suppressing CD4(+) T-cell proliferation. Taken together, our data do not support an immunoregulatory role for CD8α(+) IELs in a mouse model of small and large bowel inflammation.

Néel ordering in the distorted honeycomb pyrosilicate: C-Er2Si2O7.

The rare-earth pyrosilicate family of compounds (RE2Si2O7) hosts a variety of polymorphs, some with honeycomb-like geometries of the rare-earth sublattices, and the magnetism has yet to be deeply explored in many of the cases. Here we report on the ground state properties of C-Er2Si2O7. C-Er2Si2O7crystallizes in the C2/m space group and the Er3+atoms form a distorted honeycomb lattice in thea-bplane. We have utilized specific heat, DC susceptibility, and neutron diffraction measurements to characterize C-Er2Si2O7. Our specific heat and DC susceptibility measurements show signatures of antiferromagnetic ordering at 2.3 K. Neutron powder diffraction confirms this transition temperature and the relative intensities of the magnetic Bragg peaks are consistent with a collinear Néel state in the magnetic space group C2'/m, with ordered moment of 6.61µBcanted 13° away from thec-axis toward thea-axis. These results are discussed in relation to the isostructural quantum dimer magnet compound Yb2Si2O7.

Systems-based accident analysis in the led outdoor activity domain: application and evaluation of a risk management framework.

Safety-compromising accidents occur regularly in the led outdoor activity domain. Formal accident analysis is an accepted means of understanding such events and improving safety. Despite this, there remains no universally accepted framework for collecting and analysing accident data in the led outdoor activity domain. This article presents an application of Rasmussen's risk management framework to the analysis of the Lyme Bay sea canoeing incident. This involved the development of an Accimap, the outputs of which were used to evaluate seven predictions made by the framework. The Accimap output was also compared to an analysis using an existing model from the led outdoor activity domain. In conclusion, the Accimap output was found to be more comprehensive and supported all seven of the risk management framework's predictions, suggesting that it shows promise as a theoretically underpinned approach for analysing, and learning from, accidents in the led outdoor activity domain. STATEMENT OF RELEVANCE: Accidents represent a significant problem within the led outdoor activity domain. This article presents an evaluation of a risk management framework that can be used to understand such accidents and to inform the development of accident countermeasures and mitigation strategies for the led outdoor activity domain.

Computer vision and natural constraints.

Computer vision, the automatic construction of scene descriptions from image input data, has just entered its second decade. Approaches have varied widely, especially in the amounts of symbolic, domain-dependent knowledge and inference that are incorporated into the vision process. Much current research addresses the extraction of physical properties of the scene (depth, surface orientation, reflectance) from images by using only a few general assumptions about the scene domain. Extraction of physical parameters is part of a hierarchy of operations needed to transform image input data to symbolic descriptions. Two other processes that serve as examples are stereo fusion and the partitioning of image phenomena into related groups. Computer vision research is influencing theories of animal perception as well as the design of computing architectures for artificial intelligence.

Brain activity during speaking: from syntax to phonology in 40 milliseconds.

In normal conversation, speakers translate thoughts into words at high speed. To enable this speed, the retrieval of distinct types of linguistic knowledge has to be orchestrated with millisecond precision. The nature of this orchestration is still largely unknown. This report presents dynamic measures of the real-time activation of two basic types of linguistic knowledge, syntax and phonology. Electrophysiological data demonstrate that during noun-phrase production speakers retrieve the syntactic gender of a noun before its abstract phonological properties. This two-step process operates at high speed: the data show that phonological information is already available 40 milliseconds after syntactic properties have been retrieved.

Duffy antigen expression on reticulocytes does not alter following blood loss in an autologous donation model.

BACKGROUND: The Duffy blood group (Fy) antigen functions as the receptor whereby the malarial parasite Plasmodium vivax invades reticulocytes. In this study, we evaluated an autologous blood donation model to measure Fy expression during the anticipated response to blood loss. AIMS: This study aims to examine Fy expression following anticipated reticulocytosis in response to blood loss from autologous whole blood donation. METHOD: Subjects were healthy blood donors presenting for planned collection of two or three autologous units. Whole blood (450 ml +/- 10%) was collected and processed. Blood samples for Fy testing were obtained from the donations. These were assayed by flow cytometry by measuring binding of a phycoerythrin-labelled anti-Fy6 antibody and compared against reticulocyte numbers. Reticulocyte numbers were measured using thiazole orange. Results were compared from baseline (first donation) with samples at second and, if available, third, donations. Phenotyping for Fy a and b antigens was performed. RESULTS: Reticulocytes increased by a mean of 37% over baseline [0.93% (range 0.31-1.93) to 1.23% (0.32-3.51%)] following donation of two (n = 32) or three (n = 9) autologous whole blood units. Absolute reticulocyte count remained low. Mean and median Fy expression on mature red blood cells and reticulocytes did not change from baseline levels despite individual variation. No apparent relationship to serologically determined Fy a and/or b antigen status was present. CONCLUSION: Baseline expression of Fy antigen on mature red blood cells and reticulocytes is quite variable between individuals, but appears not to be greatly affected by mild to moderate reticulocytosis following blood loss in an autologous blood donation model.

Trimethoprim-sulfamethoxazole induced acute interstitial nephritis in renal allografts; clinical course and outcome.

BACKGROUND: Acute interstitial nephritis (AIN) secondary to trimethoprim-sulfamethoxazole (TMP-SMX) is well documented as a cause of acute renal failure in native kidneys. TMP-SMX is the standard prophylactic agent against pneumocystis carinii (PCP) used in the early post-transplant period, however, it has to date only been indirectly associated with AIN in renal allografts. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We describe eleven renal transplant patients with acute allograft dysfunction in whom a transplant biopsy demonstrated primary histopathologic features of allergic AIN, all of whom were receiving TMP-SMX in addition to other medications known to cause AIN. RESULTS: All cases occurred within 1 month of transplantation and accounted for 2.12% (11/518) of the total number of transplant biopsies performed during the study period. However, this figure increased to 10.1% (11/109) when those biopsies performed for early allograft dysfunction (< 1 month) were taken into account. After discontinuation of TMP- SMX alone, all patients had an immediate improvement in serum creatinine with excellent long term allograft function - mean improvement of serum creatinine from 465 micromol/l to 136 micromol/l at last follow-up (range 15 - 55 months). CONCLUSIONS: AIN secondary to TMP-SMX, although an uncommon cause of allograft dysfunction over the study period, accounted for over 10% of cases of allograft dysfunction within the first month of transplantation. Therefore, a high degree of clinical suspicion for TMP-SMX-induced AIN is warranted when confronted with early acute allograft dysfunction.

The relationship between obesity and fractures.

There has been very limited analysis of the relationship between obesity and fractures in the orthopaedic literature. It has been established for some years that underweight individuals are at greater risk of proximal femoral fractures but recently there has been interest in the susceptibility of obese post-menopausal females to fracture. We have undertaken an analysis of 4886 adult patients who presented with a fracture and had their BMI assessed. Analysis has confirmed the relationship between underweight individuals and proximal femoral fractures but there is also a negative association between obesity and clavicle fractures in males and females and with calcaneal fractures in females. There is a positive relationship between obesity and proximal humeral, finger phalangeal and ankle fractures in males and with humeral diaphyseal, carpal and ankle fractures in females. There was no relationship found between open or multiple fractures and obesity.