Chasing Flies: The Use of Wingbeat Frequency as a Communication Cue in Calyptrate Flies (Diptera: Calyptratae).

The incidental sound produced by the oscillation of insect wings during flight provides an opportunity for species identification. Calyptrate flies include some of the fastest and most agile flying insects, capable of rapid changes in direction and the fast pursuit of conspecifics. This flight pattern makes the continuous and close recording of their wingbeat frequency difficult and limited to confined specimens. Advances in sound editor and analysis software, however, have made it possible to isolate low amplitude sounds using noise reduction and pitch detection algorithms. To explore differences in wingbeat frequency between genera and sex, 40 specimens of three-day old Sarcophaga crassipalpis, Lucilia sericata, Calliphora dubia, and Musca vetustissima were individually recorded in free flight in a temperature-controlled room. Results showed significant differences in wingbeat frequency between the four species and intersexual differences for each species. Discriminant analysis classifying the three carrion flies resulted in 77.5% classified correctly overall, with the correct classification of 82.5% of S. crassipalpis, 60% of C. dubia, and 90% of L. sericata, when both mean wingbeat frequency and sex were included. Intersexual differences were further demonstrated by male flies showing significantly higher variability than females in three of the species. These observed intergeneric and intersexual differences in wingbeat frequency start the discussion on the use of the metric as a communication signal by this taxon. The success of the methodology demonstrated differences at the genus level and encourages the recording of additional species and the use of wingbeat frequency as an identification tool for these flies.

Domestic Filth Flies in New Haven, Connecticut: A Case Study on the Effects of Urbanization and Climate Change by Comparing Fly Populations after 78 Years.

Changes in common and widespread insect populations such as the domestic filth fly in urban cities are useful and relevant bioindicators for overall changes in the insect biomass. The current study surveyed necrophagous flies by placing a weekly trap from June-September over a two-year period in the city of New Haven, Connecticut, to compare data on fly abundance and diversity with data collected 78 years earlier. Climate and land cover changes were also assessed in combination with the fly population for each period. The survey results suggest the domestic filth fly population is now less diverse with decreased species richness and changes in the relative abundance of species. In both surveys, 95-96% of the population was composed of only three species. The current survey data indicate the numerical dominance of Lucilia sericata has decreased, the abundance of several species, notably Lucilia coeruleiviridis, has increased, and Lucilia illustris is absent. Species that showed a significant interaction with temperature in the 1940s survey have now increased in abundance, with several of the trapped species continuing to show an interaction with temperature and rainfall. Analysis of the land cover and climate data characterizes the trap site as a region exposed to a prolonged period of industrialization and urbanization, with only 7% of the land cover remaining undeveloped and over 50% impervious, coupled with an increase in temperature and rainfall. This study serves as a model for changes in domestic filth fly populations and other insects in similarly highly urbanized established cities.

Forensically relevant blow flies (Diptera: Calliphoridae) of Central Connecticut, USA.

Connecticut and the Northeastern United States in general, lacks forensically relevant entomological survey data. To determine which forensically relevant calliphorid (blow flies, Diptera: Calliphoridae) and non-calliphorid species dominate Connecticut, 5 traps using pork bait were set out 7 times over a 2-year period to collect adult and immature specimens. Insects collected from human corpses in this region were also tabulated to collaborate the forensic relevance of trapped specimens. The survey identified a total of 8 species of blow flies of the Lucilia and Calliphora genera, 6 of which colonized the baits, and 5 of which have been found to colonize human corpses in the area. Non-calliphorid genera Sarcophaga and Muscina were also found to be colonizers of the baited traps but in relatively lower numbers. Trap sites differed significantly in the degree of urbanization which was determined by using GIS mapping to classify a 1 kilometer (km) radius around each site using land use and the percent of urban impervious surfaces. The 1 km radius revealed the highly fragmented nature of the immediate habitats of the trap sites and no habitat or seasonal preference was demonstrated by blow flies under these trap conditions. Temperature was the one variable which significantly affected the number of flies trapped and the colonizing species. All trapped species have been described previously as widespread and common in the United States and as synanthropic. Further research in this region should trap at the constantly changing extreme ends of the urban-rural gradient and in the colder temperatures of winter to explore the limits of the flexibility of these blow fly species.

Overview of HOMEChem: House Observations of Microbial and Environmental Chemistry.

The House Observations of Microbial and Environmental Chemistry (HOMEChem) study is a collaborative field investigation designed to probe how everyday activities influence the emissions, chemical transformations and removal of trace gases and particles in indoor air. Sequential and layered experiments in a research house included cooking, cleaning, variable occupancy, and window-opening. This paper describes the overall design of HOMEChem and presents preliminary case studies investigating the concentrations of reactive trace gases, aerosol particles, and surface films. Cooking was a large source of VOCs, CO2, NOx, and particles. By number, cooking particles were predominantly in the ultrafine mode. Organic aerosol dominated the submicron mass, and, while variable between meals and throughout the cooking process, was dominated by components of hydrocarbon character and low oxygen content, similar to cooking oil. Air exchange in the house ensured that cooking particles were present for only short periods. During unoccupied background intervals, particle concentrations were lower indoors than outdoors. The cooling coils of the house ventilation system induced cyclic changes in water soluble gases. Even during unoccupied periods, concentrations of many organic trace gases were higher indoors than outdoors, consistent with housing materials being potential sources of these compounds to the outdoor environment. Organic material accumulated on indoor surfaces, and exhibited chemical signatures similar to indoor organic aerosol.

Short communication: Risk factors for sonographically detectable udder edema in overbagged cows at dairy shows.

At dairy cow shows, the appearance of the udder is very important. To show cows at their best, udders are often presented in an overbagged state by extending milking intervals before the show. This practice represents an animal welfare issue because it is associated with behavior changes (e.g., excessive abduction and decreased eating time) and may affect the health of the animal. The aim of the current study was to determine the association between various parameters (e.g., milk yield, days in milk, milking procedures, or administration of nonsteroidal anti-inflammatory drugs, steroids, or diuretics) and the sonographically detectable udder edema score. Data were collected from the show catalogs, by interviewing the exhibitors, by analyzing official veterinary treatment protocols and official milking data, via laboratory analysis of blood samples, and by sonographic examinations of the udders at the show. For sonographically detectable udder edema scoring, 3 scans were taken, 1 on each fore quarter and 1 incorporating both rear quarters at the level of the median suspensory ligament. For grading the scans, a scoring system of 4 grades (score 0 = no edema, 1 = slight edema, 2 = moderate edema, 3 = severe edema) was used. Data from 321 cows of different breeds were collected at 4 highly competitive Swiss dairy shows (shows A-D) between January and September 2017. To determine risk factors for sonographically detectable udder edema, data were analyzed with 2 different logistic regression models. In model 1, the odds ratios were 3.33 (milking intervals of ≥16 h vs. <14 h), 3.84 (show A vs. show C), and 7.39 (dairy breeds vs. dual-purpose breeds). Milking intervals of dairy breeds were significantly higher than those of dual-purpose breeds. In model 2, milking interval was the only significant risk factor with an odds ratio of 9.00 for milking intervals of ≥16 h. Only the milking intervals represented a relevant risk factor in both models; therefore, we concluded that the previously described sonographic udder edema scoring is a useful technique for detecting overbagged udders at dairy shows. Its routine implementation may improve cow welfare at dairy shows.

Technical Note: Real-time image-guided adaptive radiotherapy of a rigid target for a prototype fixed beam radiotherapy system.

PURPOSE: Fixed beam radiotherapy systems utilize couch movement and rotation instead of gantry rotation in order to simplify linear accelerator design. We investigate the ability to deliver fixed beam treatments with the same level of clinical accuracy as conventional (rotating beam) treatments using real-time image guidance to maintain this accuracy in the presence of rigid target motion. METHODS: A prototype fixed beam radiotherapy system was built using a standard linac with the beam fixed in the vertical position and a computer controlled rotation stage that rotated a rigid phantom about the superior-inferior axis. Kilovoltage Intrafraction Monitoring (KIM) and real-time beam adaptation with MLC tracking was applied to a five-field IMRT treatment plan with motion introduced to the phantom. The same IMRT treatment was also delivered with real-time adaptation using the conventional rotating beam geometry. Film dosimetry was used to measure the dose delivered with a fixed beam compared to a rotating beam, as well as to compare treatments delivered with and without real-time adaptation. RESULTS: The dose distributions were found to be equivalent between the fixed beam and rotating beam geometry for real-time adaptive radiotherapy using KIM and MLC tracking beam adaptation. Gamma analysis on the films showed agreement >98% using a 2%/2 mm criteria with adaptation for static shifts and periodic motion. CONCLUSIONS: Fixed beam treatments with real-time beam adaptation are dosimetrically equivalent to conventional treatments with a rotating beam, even in the presence of rigid target motion. This suggests that, for a rigid target, the high clinical accuracy of real-time adaptive radiotherapy can be achieved with simpler beam geometry.

Technical note: Evaluation of a sonographic overbagging edema scoring system for show cows: Comparison with visual inspection.

Overbagged udders are commonly seen at dairy cow shows due to prolonged milking intervals. The aims of this study were to describe the prevalence of udder edema in dairy cows at shows as determined by sonography and to suggest a sonographic scoring system, which was evaluated for reproducibility and repeatability. At 4 highly competitive Swiss dairy cow shows, 319 cows of various breeds were examined. Sonographic scans-1 from each fore quarter and 1 from the rear, representing both hind quarters-were collected by 3 experienced veterinarians at defined positions predisposed to overbagging edema. Sonographic scans were scored with the aid of a newly suggested scoring system (score 0 = no edema, grade 1 = slight edema, grade 2 = moderate edema, grade 3 = severe edema). Further, 139 video sequences from behind while the cows were walking and the same number of photographs of the udder each from the left, right, and behind were selected. The photographs and video sequences were visually scored for different parameters as 0 = not present or 1 = present except for abduction, which was scored on a visual analog scale (0 = no abduction; 100 = maximal imaginable abduction). Visual scores were then compared with the sonographic scoring (Pearson's chi-squared). The prevalence of udder edema scores 1, 2, and 3 was 14.0, 6.5, and 2.3%, respectively. Interobserver reliability for objective sonographic scoring (κ = 0.815) and intraobserver agreement (κ = 0.90 and 0.85 for 2 different observers) was estimated as "almost perfect." Interobserver agreements for visual parameters were κ = 0.40 or less except for teat shape (κ = 0.52). Classification of the videos resulted in better interobserver agreement; when rating hind limb abduction, Spearman correlation coefficient was 0.61, whereas κ = 0.61 for absence of udder movement. Udder movement and teat shape were significantly associated with the edema score. The higher inter- and intraobserver reliability of the sonographic edema scoring compared with the visual scoring system indicates that the newly suggested scoring system might be used in the future to objectively identify udder edema in cows at dairy shows.

An interdimensional correlation framework for real-time estimation of six degree of freedom target motion using a single x-ray imager during radiotherapy.

Increasing evidence suggests that intrafraction tumour motion monitoring needs to include both 3D translations and 3D rotations. Presently, methods to estimate the rotation motion require the 3D translation of the target to be known first. However, ideally, translation and rotation should be estimated concurrently. We present the first method to directly estimate six-degree-of-freedom (6DoF) motion from the target's projection on a single rotating x-ray imager in real-time. This novel method is based on the linear correlations between the superior-inferior translations and the motion in the other five degrees-of-freedom. The accuracy of the method was evaluated in silico with 81 liver tumour motion traces from 19 patients with three implanted markers. The ground-truth motion was estimated using the current gold standard method where each marker's 3D position was first estimated using a Gaussian probability method, and the 6DoF motion was then estimated from the 3D positions using an iterative method. The 3D position of each marker was projected onto a gantry-mounted imager with an imaging rate of 11 Hz. After an initial 110° gantry rotation (200 images), a correlation model between the superior-inferior translations and the five other DoFs was built using a least square method. The correlation model was then updated after each subsequent frame to estimate 6DoF motion in real-time. The proposed algorithm had an accuracy (±precision) of -0.03 ± 0.32 mm, -0.01 ± 0.13 mm and 0.03 ± 0.52 mm for translations in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) directions respectively; and, 0.07 ± 1.18°, 0.07 ± 1.00° and 0.06 ± 1.32° for rotations around the LR, SI and AP axes respectively on the dataset. The first method to directly estimate real-time 6DoF target motion from segmented marker positions on a 2D imager was devised. The algorithm was evaluated using 81 motion traces from 19 liver patients and was found to have sub-mm and sub-degree accuracy.

Quantifying the accuracy and precision of a novel real-time 6 degree-of-freedom kilovoltage intrafraction monitoring (KIM) target tracking system.

Target rotation can considerably impact the delivered radiotherapy dose depending on the tumour shape. More accurate tumour pose during radiotherapy treatment can be acquired through tracking in 6 degrees-of-freedom (6 DoF) rather than in translation only. A novel real-time 6 DoF kilovoltage intrafraction monitoring (KIM) target tracking system has recently been developed. In this study, we experimentally evaluated the accuracy and precision of the 6 DoF KIM implementation. Real-time 6 DoF KIM motion measurements were compared against the ground truth motion retrospectively derived from kV/MV triangulation for a range of lung and prostate tumour motion trajectories as well as for various static poses using a phantom. The accuracy and precision of 6 DoF KIM were calculated as the mean and standard deviation of the differences between KIM and kV/MV triangulation for each DoF, respectively. We found that KIM is able to provide 6 DoF motion with sub-degree and sub-millimetre accuracy and precision for a range of realistic tumour motion.

Using advanced mass spectrometry techniques to fully characterize atmospheric organic carbon: current capabilities and remaining gaps.

Organic compounds in the atmosphere vary widely in their molecular composition and chemical properties, so no single instrument can reasonably measure the entire range of ambient compounds. Over the past decade, a new generation of in situ, field-deployable mass spectrometers has dramatically improved our ability to detect, identify, and quantify these organic compounds, but no systematic approach has been developed to assess the extent to which currently available tools capture the entire space of chemical identity and properties that is expected in the atmosphere. Reduced-parameter frameworks that have been developed to describe atmospheric mixtures are exploited here to characterize the range of chemical properties accessed by a suite of instruments. Multiple chemical spaces (e.g. oxidation state of carbon vs. volatility, and oxygen number vs. carbon number) were populated with ions measured by several mass spectrometers, with gas- and particle-phase α-pinene oxidation products serving as the test mixture of organic compounds. Few gaps are observed in the coverage of the parameter spaces by the instruments employed in this work, though the full extent to which comprehensive measurement was achieved is difficult to assess due to uncertainty in the composition of the mixture. Overlaps between individual ions and regions in parameter space were identified, both between gas- and particle-phase measurements, and within each phase. These overlaps were conservatively found to account for little (<10%) of the measured mass. However, challenges in identifying overlaps and in accurately converting molecular formulas into chemical properties (such as volatility or reactivity) highlight a continued need to incorporate structural information into atmospheric measurements.

ESTIMATES OF RADIATION DOSES TO THE SKIN FOR PEOPLE CAMPED AT WALLATINNA DURING THE UK TOTEM 1 ATOMIC WEAPONS TEST.

A group of Aboriginal people was camped at Wallatinna in South Australia, ~170 km downwind from Emu Field, where an atomic test (the Totem 1 test) was carried out at 07.00 on 15 October 1953 local time (21.30 on 14 October 1953 GMT (Greenwich Mean Time)). They left the camp ~24 hours later. These people stated that a phenomenon that has become known as a 'black mist' rolled through their camp site ~5 hours after detonation and that some of them subsequently became sick, displaying skin reddening and nausea. They feared that the sickness was a result of exposure to high levels of radiation. The purpose of this paper is to determine if these people could have received ionising radiation doses high enough to cause the symptoms displayed. The methodology used for the dose estimates is described in the paper. The exposure modes considered were external exposure due to the passage of a contaminated plume over the camp site, inhalation of material from this plume, external exposure from material deposited on the ground as the plume passed, and consumption of contaminated food and water. The contaminants considered in the airborne cloud and the ground plume were fission products and unburnt plutonium from the nuclear detonation, and neutron activation products caused by vaporisation of the tower used to position the weapon. The source was approximated by a line source. An upper estimate of the effective doses received is ~4 mSv, which is well below the level at which acute radiation effects are observed. This estimate is consistent with earlier assessments, which did not consider inhalation of the contribution from neutron activation products.

Alpha-2 macroglobulin in Alzheimer's disease: a marker of neuronal injury through the RCAN1 pathway.

Preclinical changes that precede the onset of symptoms and eventual diagnosis of Alzheimer's disease (AD) are a target for potential preventive interventions. A large body of evidence suggests that inflammation is closely associated with AD pathogenesis and may be a promising target pathway for such interventions. However, little is known about the association between systemic inflammation and preclinical AD pathophysiology. We first examined whether the acute-phase protein, alpha-2 macroglobulin (A2M), a major component of the innate immune system, was associated with cerebrospinal fluid (CSF) markers of neuronal injury in preclinical AD and risk of incident AD in the predictors of cognitive decline among normal individuals (BIOCARD) cohort. We find that A2M concentration in blood is significantly associated with CSF concentrations of the neuronal injury markers, tau and phosphorylated tau, and that higher baseline serum A2M concentration is associated with an almost threefold greater risk of progression to clinical symptoms of AD in men. These findings were replicated in the Alzheimer's Disease Neuroimaging (ADNI) study. Then, utilizing a systems level approach combining large multi-tissue gene expression datasets with mass spectrometry-based proteomic analyses of brain tissue, we identified an A2M gene network that includes regulator of calcineurin (RCAN1), an inhibitor of calcineurin, a well-characterized tau phosphatase. A2M gene and protein expression in the brain were significantly associated with gene and protein expression levels of calcineurin. Collectively these novel findings suggest that A2M is associated with preclinical AD, reflects early neuronal injury in the disease course and may be responsive to tau phosphorylation in the brain through the RCAN1-calcineurin pathway.

Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

A single prolonged milking interval of 24h compromises the well-being and health of dairy Holstein cows.

Cows are often shown at dairy shows with overfilled udders to achieve a better show placing. However, it is unclear to what degree "over-bagging" affects the health and well-being of show cows. The goal of this study was to assess the effect of a single prolonged milking interval (PMI) of 24h on the measurable signs of health and well-being in dairy cows in early and mid-lactation and to assess the effect of a nonsteroidal anti-inflammatory drug (NSAID) on well-being during a PMI. Fifteen Holstein cows were studied in early lactation (89.5±2.7d in milk) and were given an NSAID or physiological saline in a crossover design. Ten cows were studied again in mid-lactation (151.6±4.0d in milk). Data on clinical signs of cows' health, behavior, and well-being were collected at 1 or 2h intervals before and during a PMI of 24h. Data from the last 6h of a 12h milking interval were compared with the last 6h of the PMI. Compared with that of a cow in the last 6h of a 12-h milking interval, the behavior of cows in early lactation (saline group) changed during the last 6h of the PMI: we observed decreased eating time (22.4 vs. 16.2min/h), increased ruminating time (13.3 vs. 25.0min/h), and increased hind limb abduction while walking (score 41.7 vs. 62.6) and standing (31.2 vs. 38.9cm). Udder firmness was increased (2.9 vs. 4.5kg) during this period and more weight was placed on the hind limbs (46.4 vs. 47.0%). We also found pathological signs at the end of the PMI: all cows showed milk leaking, and 10 of 15 cows developed edema in the subcutaneous udder tissue. Somatic cell count was significantly increased from 12h to 72h after the PMI. Administration of an NSAID had no influence on measured variables, except that the occurrence of edema was not significantly increased during PMI in the flunixin group (10 of 15 and 6 of 15 cows for the saline and flunixin groups, respectively). In the cows in mid-lactation, different variables were not significantly changed in the PMI compared with baseline values (e.g., eating and ruminating time, occurrence of edema, and abduction). We conclude that the cows' health and well-being were compromised by a single PMI of 24h, because their behavior changed and pathological signs were recorded. Administration of an NSAID had a slight effect on cows' well-being during a PMI. The stage of lactation had more effect on the cows' health and well-being, because fewer variables were changed in mid-lactation.

Postmortem scavenging by the Virginia opossum (Didelphis virginiana): Impact on taphonomic assemblages and progression.

The Virginia opossum (Didelphis virginiana) is a highly active scavenger whose behavior has significant impacts on rates of decomposition and skeletonization, which have previously not been addressed. In this study, scavenging by the opossum led to the skeletonization of carcasses in half of the accumulated degree days (ADD) of a comparable non-scavenged control carcass. Opossums used body orifices, as well as natural tears caused by the decomposition process, to access internal tissues and consume them. This activity resulted in little movement of the carcass and the retained appearance of natural undisturbed decomposition. This concealed activity has the potential to cause drastically incorrect estimates of time since deposition and post-mortem interval. Scavenging by opossums was also found to leave distinct tooth mark and other defects on bone, which have not been previously distinguished in the literature. This research suggests, beyond effects on PMI, that scavenging by opossums has been historically overlooked and misattributed to canid scavengers.

Diagnosis and ultrasonographic appearance of hepatic metastasis in six cases of canine appendicular osteosarcoma (2005-2013).

OBJECTIVES: The aims of this retrospective study were to identify clinical cases of dogs with appendicular osteosarcoma (OSA) in which hepatic metastasis was confirmed, to highlight the use of cytology for its diagnosis and to describe the radiographic and ultrasonographic appearances of the lesion. METHODS: Medical records were retrospectively reviewed for dogs with appendicular OSA and hepatic metastases between January 2005 and January 2013. Reviews of radiographs, ultrasounds and cytology were performed. RESULTS: Six dogs with appendicular OSA and hepatic metastases were identified. The ultrasonographic appearance of metastatic lesions varied, including hyperechoic with shadowing, hyperechoic without shadowing, hypoechoic and mixed echogenicity. In two cases, the hepatic metastases were also evident on thoracic radiographs. The mean survival time from diagnosis of appendicular OSA was 188 days (range 69-363 days) and from diagnosis of hepatic metastases was 35 days (range 2-69 days). Death was tumour-related in all cases. CONCLUSIONS: Hepatic metastasis varies widely in its ultrasonographic appearance. In three of six cases, hepatic metastasis was identified without concurrent pulmonary metastasis; therefore, abdominal ultrasound may be useful at regular intervals for patient evaluation, especially in clinical trials where accurate identification of the disease-free interval is crucial. Once hepatic metastasis is confirmed, survival times appear limited.

Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation.

Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer's disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity of Alzheimer's neuropathology. Using a prospective population-based cohort, Baltimore Longitudinal Study of Aging (BLSA), this study aims to examine the relationships between midlife body mass index (BMI) and (1) AAO of AD (2) severity of Alzheimer's neuropathology and (3) fibrillar brain amyloid deposition during aging. We analyzed data on 1394 cognitively normal individuals at baseline (8643 visits; average follow-up interval 13.9 years), among whom 142 participants developed incident AD. In two subsamples of BLSA, 191 participants underwent autopsy and neuropathological assessment, and 75 non-demented individuals underwent brain amyloid imaging. Midlife adiposity was derived from BMI data at 50 years of age. We find that each unit increase in midlife BMI predicts earlier onset of AD by 6.7 months (P=0.013). Higher midlife BMI was associated with greater Braak neurofibrillary but not CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuritic plaque scores at autopsy overall. Associations between midlife BMI and brain amyloid burden approached statistical significance. Thus, higher midlife BMI was also associated with greater fibrillar amyloid measured by global mean cortical distribution volume ratio (P=0.075) and within the precuneus (left, P=0.061; right, P=0.079). In conclusion, midlife overweight predicts earlier onset of AD and greater burden of Alzheimer's neuropathology. A healthy BMI at midlife may delay the onset of AD.

Low alanine aminotransferase levels and higher number of cardiovascular events in people with Type 2 diabetes: analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS: To determine whether alanine aminotransferase or gamma-glutamyltransferase levels, as markers of liver health and non-alcoholic fatty liver disease, might predict cardiovascular events in people with Type 2 diabetes. METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes study were analysed to examine the relationship between liver enzymes and incident cardiovascular events (non-fatal myocardial infarction, stroke, coronary and other cardiovascular death, coronary or carotid revascularization) over 5 years. RESULTS: Alanine aminotransferase measure had a linear inverse relationship with the first cardiovascular event occurring in participants during the study period. After adjustment, for every 1 sd higher baseline alanine aminotransferase measure (13.2 U/l), the risk of a cardiovascular event was 7% lower (95% CI 4-13; P = 0.02). Participants with alanine aminotransferase levels below and above the reference range 8-41 U/l for women and 9-59 U/l for men, had hazard ratios for a cardiovascular event of 1.86 (95% CI 1.12-3.09) and 0.65 (95% CI 0.49-0.87), respectively (P = 0.001). No relationship was found for gamma-glutamyltransferase. CONCLUSIONS: The data may indicate that in people with Type 2 diabetes, which is associated with higher alanine aminotransferase levels because of prevalent non-alcoholic fatty liver disease, a low alanine aminotransferase level is a marker of hepatic or systemic frailty rather than health.