To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Obtaining objective, dietary exposure information from individuals is challenging because of the complexity of food consumption patterns and the limitations of self-reporting tools (e.g., FFQ and diet diaries). This hinders research efforts to associate intakes of specific foods or eating patterns with population health outcomes.
Dietary exposure can be assessed by the measurement of food-derived chemicals in urine samples. We aimed to develop methodologies for urine collection that minimised impact on the day-to-day activities of participants but also yielded samples that were data-rich in terms of targeted biomarker measurements.
Urine collection methodologies were developed within home settings.
Different cohorts of free-living volunteers.
Home collection of urine samples using vacuum transfer technology was deemed highly acceptable by volunteers. Statistical analysis of both metabolome and selected dietary exposure biomarkers in spot urine collected and stored using this method showed that they were compositionally similar to urine collected using a standard method with immediate sample freezing. Even without chemical preservatives, samples can be stored under different temperature regimes without any significant impact on the overall urine composition or concentration of forty-six exemplar dietary exposure biomarkers. Importantly, the samples could be posted directly to analytical facilities, without the need for refrigerated transport and involvement of clinical professionals.
This urine sampling methodology appears to be suitable for routine use and may provide a scalable, cost-effective means to collect urine samples and to assess diet in epidemiological studies.
Introduction: Prehospital sepsis alerts assist paramedics in identifying patients with sepsis and in communicating this diagnosis to receiving facilities. Following the prospective implementation study of our regional systemic inflammatory response syndrome-based alert criteria (Alert), the purpose of this sub-study was to determine the cause of Alert false negatives (patients without an Alert that subsequently met sepsis criteria in the Emergency Department (ED)). Additionally, the sensitivity of the Alert for detecting sepsis was compared to the Quick Sequential Organ Failure Assessment (qSOFA) and Hamilton Early Warning Score (HEWS). Methods: This study was an additional analysis of the prospective Alert implementation study. Included patients were ≥ 18 years old, transported by a regional Emergency Medical Service and met severe sepsis or septic shock criteria (SS/SS, 2012 Surviving Sepsis Guidelines) in regional EDs in 2013. False negative patients were identified prospectively and reviewed by comparing paramedic determined Alert status to the retrospective application of the Alert criteria to Paramedic Call Report (PCR) data. The Alert sensitivity was first calculated from prospective data, then retrospective sensitivities of the Alert, qSOFA and HEWS were calculated by retrospectively applying these tools to PCRs, using ED diagnosis of SS/SS as reference standard. Results: In 2013, 229 patients met SS/SS criteria in the ED and had PCRs available; 115 (50.2%) were male and median age [interquartile range] was 76.0 [63.0-84.0]. Of 229, 149 (65.0%) arrived in the ED without an Alert (false negatives) and 46 (30.9%) of these met Alert criteria retrospectively and were therefore missed by paramedics. Sensitivity of the Alert was 34.9% when applied by paramedics and 41.5% when applied retrospectively to PCRs. The retrospective sensitivities of the qSOFA and HEWS were 37.6% and 67.7%, respectively. Conclusion: In ED patients diagnosed with SS/SS who arrived with no Alert, the majority (69.1%) were missed by the Alert criteria, rather than by paramedic application of the tool. The Alert had a sensitivity of 34.9%. When applied retrospectively and compared to the Alert, qSOFA had similar sensitivity and HEWS had increased sensitivity. Future research should focus on deriving improved alerts or implementing those with higher accuracy, such as HEWS.
There is strong evidence that foods containing dietary fibre protect against colorectal cancer, resulting at least in part from its anti-proliferative properties. This study aimed to investigate the effects of supplementation with two non-digestible carbohydrates, resistant starch (RS) and polydextrose (PD), on crypt cell proliferative state (CCPS) in the macroscopically normal rectal mucosa of healthy individuals. We also investigated relationships between expression of regulators of apoptosis and of the cell cycle on markers of CCPS. Seventy-five healthy participants were supplemented with RS and/or PD or placebo for 50 d in a 2 × 2 factorial design in a randomised, double-blind, placebo-controlled trial (the Dietary Intervention, Stem cells and Colorectal Cancer (DISC) Study). CCPS was assessed, and the expression of regulators of the cell cycle and of apoptosis was measured by quantitative PCR in rectal mucosal biopsies. SCFA concentrations were quantified in faecal samples collected pre- and post-intervention. Supplementation with RS increased the total number of mitotic cells within the crypt by 60 % (P = 0·001) compared with placebo. This effect was limited to older participants (aged ≥50 years). No other differences were observed for the treatments with PD or RS as compared with their respective controls. PD did not influence any of the measured variables. RS, however, increased cell proliferation in the crypts of the macroscopically-normal rectum of older adults. Our findings suggest that the effects of RS on CCPS are not only dose, type of RS and health status-specific but are also influenced by age.
CompStat emerged in the mid 1990s and quickly came to be seen as a major innovation in American policing. By the turn of the century it had received national awards from Harvard University and former Vice President Gore, and was featured prominently along with William Bratton (the police administrator who created the program) in the national news media. Its originators and proponents gave CompStat credit for impressive reductions in crime and improvements in neighborhood quality of life in a number of cities that had adopted the program (Silverman, 1996; Remnick, 1997; Gurwitt, 1998; Bratton, 1999). And while CompStat was first introduced only in 1994 in New York City, police departments around the country had begun to adopt it or variations of it by the first decade of the new century (Law Enforcement News, 1997; Maas, 1998; McDonald, 1998; Weisburd et al., 2003; Willis, Mastrofski & Kochel, 2010a). Indeed, in a Police Foundation survey conducted only six years after CompStat emerged on the scene in New York City, more than a third of American police agencies with 100 or more sworn officers claimed to have implemented a CompStat-like program (Weisburd et al., 2001). By 2006, Willis, Mastrofski, and Kochel (2010b) reported that about 60 percent of large police agencies had adopted CompStat, and a Police Executive Research Forum membership survey in 2011 reported that 85 percent of 166 responding member agencies reported having adopted or plans to adopt CompStat (Bureau of Justice Assistance & Police Executive Research Forum, 2013). Drawing on this survey and the comments of police leaders, researchers, and others attending a conference on CompStat in 2013, a report on the meeting offered a uniformly positive assessment of CompStat’s performance to date, as well as its future potential: “Regardless of how it develops in the future, it is clear that Compstat has become an integral part of policing in the United States by helping agencies become more productive, agile, and effective” (BJA & PERF, 2013: 30).
Bowel cancer risk is strongly influenced by lifestyle factors including diet and physical activity. Several studies have investigated the effects of adherence to the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) cancer prevention recommendations on outcomes such as all-cause and cancer-specific mortality, but the relationships with molecular mechanisms that underlie the effects on bowel cancer risk are unknown. This study aimed to investigate the relationships between adherence to the WCRF/AICR cancer prevention recommendations and wingless/integrated (WNT)-pathway-related markers of bowel cancer risk, including the expression of WNT pathway genes and regulatory microRNA (miRNA), secreted frizzled-related protein 1 (SFRP1) methylation and colonic crypt proliferative state in colorectal mucosal biopsies. Dietary and lifestyle data from seventy-five healthy participants recruited as part of the DISC Study were used. A scoring system was devised including seven of the cancer prevention recommendations and smoking status. The effects of total adherence score and scores for individual recommendations on the measured outcomes were assessed using Spearman’s rank correlation analysis and unpaired t tests, respectively. Total adherence score correlated negatively with expression of Myc proto-oncogene (c-MYC) (P=0·039) and WNT11 (P=0·025), and high adherers had significantly reduced expression of cyclin D1 (CCND1) (P=0·042), WNT11 (P=0·012) and c-MYC (P=0·048). Expression of axis inhibition protein 2 (AXIN2), glycogen synthase kinase (GSK3β), catenin β1 (CTNNB1) and WNT11 and of the oncogenic miRNA miR-17 and colonic crypt kinetics correlated significantly with scores for individual recommendations, including body fatness, red meat intake, plant food intake and smoking status. The findings from this study provide evidence for positive effects of adherence to the WCRF/AICR cancer prevention recommendations on WNT-pathway-related markers of bowel cancer risk.
Depression and metabolic syndrome (MetS) are frequently comorbid disorders that are independently associated with premature mortality. Conversely, cardiorespiratory fitness (CRF) is associated with reduced mortality risk. These factors may interact to impact mortality; however, their effects have not been assessed concurrently. This analysis assessed the mortality risk of comorbid depression/MetS and the effect of CRF on mortality in those with depression/MetS.
Prospective study of 47 702 adults in the Cooper Center Longitudinal Study. Mortality status was attained from the National Death Index. History of depression was determined by patient response (yes or no) to a standardized medical history questionnaire. MetS was categorized using the American Heart Association/National Heart, Lung, and Blood Institute criteria. CRF was estimated from the final speed/grade of a treadmill graded exercise test.
13.9% reported a history of depression, 21.4% met criteria for MetS, and 3.0% met criteria for both MetS and history of depression. History of depression (HR = 1.24, p = 0.003) and MetS (HR = 1.28, p < 0.001) were independently associated with an increased mortality risk, with the greatest mortality risk among individuals with both a history of depression and MetS (HR = 1.59, p < 0.001). Higher CRF was associated with a significantly lower risk of mortality (p < 0.001) in all individuals, including those with MetS and/or a history of depression.
Those with higher levels CRF had reduced mortality risk in the context of depression/MetS. Interventions that improve CRF could have substantial impact on the health of persons with depression/MetS.
The purpose of this study was to investigate the microbiological quality of liver pâté. During 2012–13, a total of 870 samples, unrelated to the investigation of food-poisoning outbreaks, were collected either at retail (46%), catering (53%) or the point of manufacture (1%) and were tested using standard methods to detect Salmonella spp. or Campylobacter spp., and to enumerate for Listeria spp., including Listeria monocytogenes, Clostridium perfringens, coagulase-positive staphylococci including Staphylococcus aureus, Bacillus spp., including Bacillus cereus, Escherichia coli, Enterobacteriaceae, and aerobic colony counts (ACCs). Seventy-three percent of samples were of satisfactory microbiological quality, 18% were borderline and 9% unsatisfactory. Salmonella spp. or Campylobacter spp. was not recovered from any sample. The most common causes of unsatisfactory results were elevated ACCs (6% of the samples) and high Enterobacteriaceae counts (4% of samples). The remaining unsatisfactory results were due to elevated counts of: E. coli (three samples); B. cereus (one sample at 2·6 × 105 cfu/g); or L. monocytogenes (one sample at 2·9 × 103 cfu/g). Pâté from retail was less likely to be contaminated with L. monocytogenes than samples collected from catering and samples from supermarkets were of significantly better microbiological quality than those from catering establishments.
The accurate and precise collection of three-dimensional (3D) context and provenience data is of critical importance for archaeologists. Traditional square-hole methods are being augmented by new digital techniques to increase the accuracy and precision with which 3D data are collected. Structure from Motion (SfM) photogrammetry is an emerging digital technique that is becoming more widespread for collecting 3D data of archaeological sites and features. We are using handheld digital cameras and ground-based SfM to record accurate and precise 3D context and provenience data at the scale of the excavation unit and profile during rockshelter excavations in the Lower Pecos Canyonlands of Texas. By combining SfM with traditional excavation methods, we collect 3D data on excavation units, layers, features, and profiles without excavating in grid-bound square units. SfM provides a straightforward and flexible method to excavate based on the stratigraphy and logistical pragmatics, which further aids in assigning precise context and provenience to recovered artifacts and samples. This article describes how ground-based SfM serves as a basic recording tool during excavation and shows that, by applying ground-based SfM methods to excavation, archaeologists can collect more, and more accurate, data than with traditional square-hole methods.
We use the structure lattice, introduced in Part I, to undertake a systematic study of the class
consisting of compactly generated, topologically simple, totally disconnected locally compact groups that are nondiscrete. Given
, we show that compact open subgroups of
involve finitely many isomorphism types of composition factors, and do not have any soluble normal subgroup other than the trivial one. By results of Part I, this implies that the centralizer lattice and local decomposition lattice of
are Boolean algebras. We show that the
-action on the Stone space of those Boolean algebras is minimal, strongly proximal, and microsupported. Building upon those results, we obtain partial answers to the following key problems: Are all groups in
abstractly simple? Can a group in
be amenable? Can a group in
be such that the contraction groups of all of its elements are trivial?
The ultrafast charge dynamics following the interaction of an ultra-intense laser pulse with a foil target leads to the launch of an ultra-short, intense electromagnetic (EM) pulse along a wire connected to the target. Due to the strong electric field (of the order of
) associated to such laser-driven EM pulses, these can be exploited in a travelling-wave helical geometry for controlling and optimizing the parameters of laser accelerated proton beams. The propagation of the EM pulse along a helical path was studied by employing a proton probing technique. The pulse-carrying coil was probed along two orthogonal directions, transverse and parallel to the coil axis. The temporal profile of the pulse obtained from the transverse probing of the coil is in agreement with the previous measurements obtained in a planar geometry. The data obtained from the longitudinal probing of the coil shows a clear evidence of an energy dependent reduction of the proton beam divergence, which underpins the mechanism behind selective guiding of laser-driven ions by the helical coil targets.
be a totally disconnected, locally compact group. A closed subgroup of
is locally normal if its normalizer is open in
. We begin an investigation of the structure of the family of closed locally normal subgroups of
. Modulo commensurability, this family forms a modular lattice
, called the structure lattice of
. We show that
admits a canonical maximal quotient
for which the quasicentre and the abelian locally normal subgroups are trivial. In this situation
has a canonical subset called the centralizer lattice, forming a Boolean algebra whose elements correspond to centralizers of locally normal subgroups. If
is second-countable and acts faithfully on its centralizer lattice, we show that the topology of
is determined by its algebraic structure (and thus invariant by every abstract group automorphism), and also that the action on the Stone space of the centralizer lattice is universal for a class of actions on profinite spaces. Most of the material is developed in the more general framework of Hecke pairs.
There is a paucity of information on the risk from potable water in non-passenger merchant vessels (NPMVs) particularly with regard to Legionella and other bacteria. This retrospective study examined water samples from 550 NPMVs docked in eight UK ports. A total of 1027 samples from 412 NPMVs were examined for total aerobic colony counts (ACC), coliforms, Escherichia coli and enterococci; 41% of samples yielded ACC above the action level (>1 × 103 c.f.u./ml) and 4·5% contained actionable levels (>1 c.f.u./100 ml) of faecal indicator bacteria. Eight hundred and three samples from 360 NPMVs were cultured specifically for Legionella and 58% of vessels proved positive for these organisms with 27% of samples showing levels greater than the UK upper action limit of 1 × 103 c.f.u./l. Cabin showers (49%) and hospital shower (45%) were frequently positive. A subset of 106 samples was analysed by quantitative polymerase chain reaction for Legionella and identified a further 11 Legionella-positive NPMVs, returning a negative predictive value of 100%. There was no correlation between NPMV age or size and any microbial parameters (P > 0·05). Legionella pneumophila serogroup 1 was isolated from 46% of NPMVs and sequence-based typing of 17 isolates revealed four sequence types (STs) previously associated with human disease. These data raise significant concerns regarding the management of microbial and Legionella risks on board NPMVs and suggest that better guidance and compliance are required to improve control.
Earth is the only planet known to harbor life, therefore we may speculate on how the nature of the Sun-Earth interaction is relevant to life on Earth, and how the behavior of other stars may influence the development of life on their planetary systems. We study the long-term variability of a sample of five solar analog stars using composite chromospheric activity records up to 50 years in length and synoptic visible-band photometry about 20 years long. This sample covers a large range of stellar ages which we use to represent the evolution in activity for solar mass stars. We find that young, fast rotators have an amplitude of variability many times that of the solar cycle, while old, slow rotators have very little variability. We discuss the possible impacts of this variability on young Earth and exoplanet climates.
We present an age-structured mathematical model of malaria and pneumonia to study the effect of two capacity-building interventions: Integrated Management of Infectious Diseases (IMID) and On-site Support Services (OSS). IMID leads to a reduction in malaria prevalence by more than 2·4% across the [0,5), [5,14) and [14,50) age groups. IMID + OSS reduces it by more than 16·0% across all age groups. IMID decreases pneumonia prevalence by more than 3·0% across all age groups while IMID + OSS decreases it by more than 1·0% across all age groups. The number of malaria and pneumonia deaths is reduced by 7·8% by IMID across all age groups and IMID + OSS decreases this number by 30·5% across all age groups, which translates to saving a life of a child per month. Prevalence of malaria-pneumonia for the [0,5) age group is 0·52% at baseline, and IMID and IMID + OSS reduce it by 6·6% and 23·6%, respectively. There is no change in incidence of malaria or pneumonia disease episodes. The results also indicate that triaging of children contributes more than 50% to the effect of the interventions in reduction of deaths and a range of 14–91% in reduction of disease cases.
Nickel–molybdenum (Ni–Mo) materials are widely used functional oxide catalysts for the hydrogen evolution reaction. In this work, we investigate the high activity of Ni–Mo by depositing size-controlled Ni nanocrystals (NCs) onto Mo substrates. We observe a synergistic increase in catalytic activity that does not scale with the Ni–Mo interface length. This evidence points to a bulk electronic interaction of the two metals that is separate from the mechanism of enhancement seen in conventionally co-deposited Ni–Mo electrocatalysts. In addition to elucidating the catalytic behavior of the Ni–Mo system, this work offers a general NC-based paradigm for investigating fundamental interactions and synergistic effects in electrocatalytic materials.
On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2–73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.
Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.