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Carbohydrate foods with high glycaemic index (GI) and load (GL) may negatively influence cancer risk. We studied the association of dietary carbohydrates, GI, GL, intake of bread and pasta with risk of bladder cancer using data from an Italian case–control study. The study included 578 men and women with histologically confirmed bladder cancer and 608 controls admitted to the same hospitals as cases for acute, non-neoplastic conditions. OR were estimated by logistic regression models after allowance for relevant confounding factors. OR of bladder cancer for the highest v. the lowest quantile of intake were 1·52 (95 % CI 0·85, 2·69) for available carbohydrates, 1·18 (95 % CI 0·83, 1·67) for GI, 1·96 (95 % CI 1·16, 3·31, Ptrend<0·01) for GL, 1·58 (95 % CI 1·09, 2·29, Ptrend=0·03) for pasta and 1·92 (95 % CI 1·28, 2·86, Ptrend<0·01) for bread. OR for regular consumption of legumes and whole-grain products were 0·78 (95 % CI 0·60, 1·00) and 0·82 (95 % CI 0·63, 1·08), respectively. No heterogeneity in risks emerged across strata of sex. This case–control study showed that bladder cancer risk was directly associated with high dietary GL and with consumption of high quantity of refined carbohydrate foods, particularly bread. These associations were apparently stronger in subjects with low vegetable consumption.
The polarization behaviour of radar waves transmitted through two Antarctic ice shelves has been investigated using a step frequency radar with a centre frequency of 300 MHz and a bandwidth of 150 MHz. One site was on Brunt Ice Shelf at a site near Halley station, and 17 sites were on George VI Ice Shelf near the southern ice front. Birefringence in the ice dominated the behaviour on Brunt Ice Shelf, where the anisotropy in the effective permittivity was found to be about 0.14%. On George VI Ice Shelf, a highly anisotropic reflecting surface was the controlling feature, suggesting a fluted ice-shelf base formed by oceanographic currents.
Limitations of access have long restricted exploration and investigation of the cavities beneath ice shelves to a small number of drillholes. Studies of sea-ice underwater morphology are limited largely to scientific utilization of submarines. Remotely operated vehicles, tethered to a mother ship by umbilical cable, have been deployed to investigate tidewater-glacier and ice-shelf margins, but their range is often restricted. The development of free-flying autonomous underwater vehicles (AUVs) with ranges of tens to hundreds of kilometres enables extensive missions to take place beneath sea ice and floating ice shelves. Autosub2 is a 3600 kg, 6.7 m long AUV, with a 1600 m operating depth and range of 400 km, based on the earlier Autosub1 which had a 500 m depth limit. A single direct-drive d.c. motor and five-bladed propeller produce speeds of 1–2 m s−1. Rear-mounted rudder and stern-plane control yaw, pitch and depth. The vehicle has three sections. The front and rear sections are free-flooding, built around aluminium extrusion space-frames covered with glass-fibre reinforced plastic panels. The central section has a set of carbon-fibre reinforced plastic pressure vessels. Four tubes contain batteries powering the vehicle. The other three house vehicle-control systems and sensors. The rear section houses subsystems for navigation, control actuation and propulsion and scientific sensors (e.g. digital camera, upward-looking 300 kHz acoustic Doppler current profiler, 200 kHz multibeam receiver). The front section contains forward-looking collision sensor, emergency abort, the homing systems, Argos satellite data and location transmitters and flashing lights for relocation as well as science sensors (e.g. twin conductivity–temperature–depth instruments, multibeam transmitter, sub-bottom profiler, AquaLab water sampler). Payload restrictions mean that a subset of scientific instruments is actually in place on any given dive. The scientific instruments carried on Autosub are described and examples of observational data collected from each sensor in Arctic or Antarctic waters are given (e.g. of roughness at the underside of floating ice shelves and sea ice).
We present newly acquired airborne radar data showing ice thickness and surface elevation for Pine Island Glacier, Antarctica. These data, when combined with earlier measurements, suggest the presence of a lightly grounded area immediately above the grounding line of Pine Island Glacier. We identify this region as an “ice plain”. It lies close to the centre line of the glacier, has an elevation above buoyancy of <50 m and extends inland for >28 km. The upstream edge of the ice plain is defined by a “coupling line”. The configuration of the ice plain implies that nearby thinning of the ice stream would result in substantial grounding-line retreat. We suggest that the grounding-line retreat of Pine Island Glacier, observed between 1992 and 1996, probably commenced sometime after 1981.
Fetal growth restriction (FGR) and preterm birth are frequent co-morbidities, both are independent risks for brain injury. However, few studies have examined the mechanisms by which preterm FGR increases the risk of adverse neurological outcomes. We aimed to determine the effects of prematurity and mechanical ventilation (VENT) on the brain of FGR and appropriately grown (AG, control) lambs. We hypothesized that FGR preterm lambs are more vulnerable to ventilation-induced acute brain injury. FGR was surgically induced in fetal sheep (0.7 gestation) by ligation of a single umbilical artery. After 4 weeks, preterm lambs were euthanized at delivery or delivered and ventilated for 2 h before euthanasia. Brains and cerebrospinal fluid (CSF) were collected for analysis of molecular and structural indices of early brain injury. FGRVENT lambs had increased oxidative cell damage and brain injury marker S100B levels compared with all other groups. Mechanical ventilation increased inflammatory marker IL-8 within the brain of FGRVENT and AGVENT lambs. Abnormalities in the neurovascular unit and increased blood–brain barrier permeability were observed in FGRVENT lambs, as well as an altered density of vascular tight junctions markers. FGR and AG preterm lambs have different responses to acute injurious mechanical ventilation, changes which appear to have been developmentally programmed in utero.
Research on presidential distributive politics focuses almost exclusively on federal domestic spending. Yet, presidential influence on public policy extends well-beyond grant allocation. Since the early 20th Century, for example, the president has had substantial discretion to adjust tariff schedules and non-tariff barriers “with the stroke of a pen.” These trade adjustments via presidential directive allow us to test the logic of presidential particularism in an area of policy understudied among presidency scholars. We examine unilateral adjustments to US trade policies between 1917 and 2006, with a detailed analysis of those made between 1986 and 2006, and find that presidents—in accordance with electoral incentives—strategically allocate trade protections to industries in politically valuable states. In general, states in which the president lacks a comfortable electoral majority are systematically more likely to receive protectionist unilateral orders. Overall, our results show that the president’s distributive imperative extends into the realm of foreign affairs, an arena in which the president has substantial authority to influence public policy.
For most common infections requiring hospitalization, antibiotic treatment is completed after hospital discharge. Postdischarge therapy is often unnecessarily broad spectrum and prolonged. We developed an intervention to improve antibiotic selection and shorten treatment durations.
Single center, quasi-experimental retrospective cohort study
Patients prescribed oral antibiotics at hospital discharge before (July 2012–June 2013) and after (October 2014–February 2015) an intervention consisting of (1) institutional guidance for oral step-down antibiotic selection and duration of therapy and (2) pharmacy audit of discharge prescriptions with real-time prescribing recommendations to providers. The primary outcomes measured were total prescribed duration of therapy and use of antibiotics with broad gram-negative activity (ie, fluoroquinolones or amoxicillin-clavulanate).
Overall, 300 cases from the preintervention period and 200 cases from the intervention period were included. Compared with the preintervention period, the use of antibiotics with broad gram-negative activity decreased during the intervention (51% vs 40%; P=.02), particularly fluoroquinolones (38% vs 25%; P=.002). The total duration of therapy decreased from a median of 10 days (interquartile range [IQR], 7–13 days) to 9 days (IQR, 6–13 days) but did not reach statistical significance (P=.13). However, the duration prescribed at discharge declined from 6 days (IQR, 4–10 days) to 5 days (IQR, 3–7 days) (P=.003). During the intervention, there was a nonsignificant increase in the overall appropriateness of discharge prescriptions from 52% to 66% (P=.15).
A multifaceted intervention to optimize antibiotic prescribing at hospital discharge was associated with less frequent use of antibiotics with broad gram-negative activity and shorter postdischarge treatment durations.
The purpose of this study was to evaluate a programme of lesion surgery carried out on patients with treatment-resistant depression (TRD).
This was a retrospective study looking at clinical and psychometric data from 45 patients with TRD who had undergone bilateral stereotactic anterior capsulotomy surgery over a period of 15 years, with the approval of the Mental Health Act Commission (37 with unipolar depression and eight with bipolar disorder). The Beck Depression Inventory (BDI) before and after surgery was used as the primary outcome measure. The Montgomery–Asberg Depression Rating Scale was administered and cognitive aspects of executive and memory functions were also examined. We carried out a paired-samples t test on the outcome measures to determine any statistically significant change in the group as a consequence of surgery.
Patients improved on the clinical measure of depression after surgery by −21.20 points on the BDI with a 52% change. There were no significant cognitive changes post-surgery. Six patients were followed up in 2013 by phone interview and reported a generally positive experience. No major surgical complications occurred.
With the limitations of an uncontrolled, observational study, our data suggest that capsulotomy can be an effective treatment for otherwise TRD. Performance on neuropsychological tests did not deteriorate.
Having worked on several approaches to CO2 capture over the past decade, we have studied a great number of physical and chemical solvents as well as polymer and composite membranes. Initially, most of these materials were based upon ionic liquids (ILs), however due to challenges encountered in applying ILs to meet the demanding requirements in CO2 separation processes, there is a need to reconsider what role (if any) ILs might play in CO2 capture technologies. Ultimately, more promising and robust materials will not come from ILs themselves, but from retrosynthetic analysis and a reconsideration of which structural variables and properties are (and are not) important. The hybridization of the constituent parts into entirely new, yet seemingly familiar substances, can yield greatly improved properties and economics. This manuscript highlights recent work from our group based on lessons learned from ILs that have spurred the development of new amine solvents and polymer materials to better address the demanding process conditions and requirements of CO2 capture and related separations.
Although the Great Basin of North America has produced some of the most robust and ancient fiber artifact assemblages in the world, many were recovered with poor chronological controls. Consequently, this class of artifacts has seldom been effectively incorporated into general discussions of early chronological and cultural patterns. In recent years, the Great Basin Textile Dating Project has accumulated direct AMS dates on textiles (bags, sandals, mats, cordage, and basketry) from dry caves in the Great Basin, particularly in the northern and western areas. We focus here on the terminal Pleistocene/early Holocene, to identify chronological patterns in this class of artifacts and to evaluate Adovasio’s characterization of the region’s earliest basketry as simple and undecorated. New AMS dates now suggest that the region’s earliest people had sophisticated textile traditions that incorporated numerous decorative elaborations. Some distinctive structures, including Fort Rock sandals and weft-faced plaited textiles, have limited early temporal ranges and may serve as diagnostic indicators for terminal Pleistocene/early Holocene times. Other basketry forms and structures that appear by about 9000 cal B.P. persist into the historic period, suggesting a stronger thread of continuity (especially in the north) from this time than is apparent in lithic traditions
Fifteen confirmed cases and 15 possible cases of Shiga toxin-producing Escherichia coli (STEC) O157 phage type 21/28 were linked to direct contact with lambs at a ‘Lambing Live’ event in the North West of England between 29 March and 21 April 2014. Twenty-one (70%) of the cases were female, 23 (77%) were children aged <16 years, of whom 14 (46%) were in the 0–5 years age group. Five children developed haemolytic uraemic syndrome. Multilocus variable number tandem repeat analysis (MLVA) profiles on 14 human cases were indistinguishable, and 6/10 animal isolates had a MLVA profile identical to the outbreak profile. Whole-genome sequencing analysis revealed that all isolates, both human and animal, fell within a 5-single nucleotide polymorphism cluster indicating the isolates belonged to the same point source. On inspection of the premises, extensive and uncontrolled physical contact between visitors and animals was occuring within the animal pens and during bottle-feeding. Public areas were visibly contaminated with animal faeces. Information to visitors, and the infection control awareness demonstrated by staff, was inadequate. Managing the risk to visitors of STEC O157 infection at animal petting events and open farms requires implementation of stringent control measures by the operator, as outlined in the industry code of practice. Enforcement action is sometimes required to prevent high-risk activities taking place at both permanent and temporary attractions.
We describe a space VLBI experiment involving an earth-orbiting satellite (SURFSAT) and simulated satellites, a space VLBI ground tracking station, an array of ground radio telescopes, and a space VLBI correlator. The purpose of this experiment was to provide as complete as possible an end-to-end simulation of space VLBI in preparation for the first space VLBI mission, VSOP, and in particular to test the most critical aspect of space VLBI, viz. the ability to generate a stable and accurate frequency standard (clock) for the orbiting VLBI element.
Five cases of STEC O157 phage type (PT) 21/28 reported consumption of raw cows' drinking milk (RDM) produced at a dairy farm in the South West of England. STEC O157 PT21/28 was isolated from faecal specimens from milking cows on the implicated farm. Whole genome sequencing (WGS) showed that human and cattle isolates were the same strain. Further analysis of WGS data confirmed that sequences of isolates from an additional four cases (who did not report consumption of RDM when first questioned) fell within the same five single nucleotide polymorphism cluster as the initial five cases epidemiologically linked to the consumption of RDM. These four additional cases identified by WGS were investigated further and were, ultimately, associated with the implicated farm. The RDM outbreak strain encoded stx2a, which is associated with increased pathogenicity and severity of symptoms. Further epidemiological analysis showed that 70% of isolates within a wider cluster containing the outbreak strain were from cases residing in, or linked to, the same geographical region of England. During this RDM outbreak, use of WGS improved case ascertainment and provided insights into the evolution of a highly pathogenic clade of STEC O157 PT21/28 stx2a associated with the South West of England.
Compound specific radiocarbon measurements can be made instantaneously using a gas chromatograph (GC) combustion system coupled to a 14C AMS system fitted with a gas ion source. Samples below 10 μg C can be analyzed but the precision is reduced to 5–10% because of lower source efficiency. We modified our GC for CH4 and CO2 analysis and injected samples multiple times to sum data and increase precision. We attained a maximum precision of 0.6% for modern CO2 from 25 injections of 27 μg C and a background of ≃0.5% (40 kyr) for ancient methane. The 14C content of dissolved CO2 and CH4 in water samples collected at a deep-sea hydrothermal vent and a serpentine mud volcano was measured and the results for the vent sample are consistent with previously published data. Further experiments are required to determine a calibration and correction procedure to maximize accuracy.
Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes.
Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted.
Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN.
This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.
To investigate biomarkers of nutrition associated with chronic disease absence for an Aboriginal cohort.
Screening for nutritional biomarkers was completed at baseline (1995). Evidence of chronic disease (diabetes, CVD, chronic kidney disease or hypertension) was sought from primary health-care clinics, hospitals and death records over 10 years of follow-up. Principal components analysis was used to group baseline nutritional biomarkers and logistic regression modelling used to investigate associations between the principal components and chronic disease absence.
Three Central Australian Aboriginal communities.
Aboriginal people (n 444, 286 of whom were without chronic disease at baseline) aged 15–82 years.
Principal components analysis grouped twelve nutritional biomarkers into four components: ‘lipids’; ‘adiposity’; ‘dietary quality’; and ‘habitus with inverse quality diet’. For the 286 individuals free of chronic disease at baseline, lower adiposity, lower lipids and better dietary quality components were each associated with the absence at follow-up of most chronic diseases examined, with the exception of chronic kidney disease. Low ‘adiposity’ component was associated with absence of diabetes, hypertension and CVD at follow-up. Low ‘lipid’ component was associated with absence of hypertension and CVD, and high ‘dietary quality’ component was associated with absence of CVD at follow-up.
Lowering or maintenance of the factors related to ‘adiposity’ and ‘lipids’ to healthy thresholds and increasing access to a healthy diet appear useful targets for chronic disease prevention for Aboriginal people in Central Australia.
Various foods are associated with effects against metabolic diseases such as insulin resistance and type 2 diabetes; however, their mechanisms of action are mostly unclear. Fatty acids may contribute by acting as precursors of signalling molecules or by direct activity on receptors. The medium- and long-chain NEFA receptor FFA1 (free fatty acid receptor 1, previously known as GPR40) has been linked to enhancement of glucose-stimulated insulin secretion, whereas FFA4 (free fatty acid receptor 4, previously known as GPR120) has been associated with insulin-sensitising and anti-inflammatory effects, and both receptors are reported to protect pancreatic islets and promote secretion of appetite and glucose-regulating hormones. Hypothesising that FFA1 and FFA4 mediate therapeutic effects of dietary components, we screened a broad selection of NEFA on FFA1 and FFA4 and characterised active compounds in concentration–response curves. Of the screened compounds, pinolenic acid, a constituent of pine nut oil, was identified as a relatively potent and efficacious dual FFA1/FFA4 agonist, and its suitability for further studies was confirmed by additional in vitro characterisation. Pine nut oil and free and esterified pure pinolenic acid were tested in an acute glucose tolerance test in mice. Pine nut oil showed a moderately but significantly improved glucose tolerance compared with maize oil. Pure pinolenic acid or ethyl ester gave robust and highly significant improvements of glucose tolerance. In conclusion, the present results indicate that pinolenic acid is a comparatively potent and efficacious dual FFA1/FFA4 agonist that exerts antidiabetic effects in an acute mouse model. The compound thus deserves attention as a potential active dietary ingredient to prevent or counteract metabolic diseases.
We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008–September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005–June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures.
During the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes.
In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.