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 email@example.com
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.
Infectious diseases, such as Helicobacter pylori, which produce systemic inflammation may be one key factor in the onset of autoimmunity. The association between H. pylori and antinuclear antibodies (ANA), a marker of autoimmunity, has been understudied. Data from the 1999–2000 National Health and Nutrition Examination Survey were used to evaluate the cross-sectional association between H. pylori seroprevalence and ANA positivity in US adults aged ≥20 years. ANA was measured in a 1:80 dilution of sera by indirect immunofluorescence using HEp-2 cells (positive ⩾3). H. pylori immunoglobulin G enzyme-linked immunosorbent assays were used to categorise individuals as seropositive or seronegative. H. pylori seropositivity and ANA positivity were common in the adult US population, with estimated prevalences of 33.3% and 9.9%, respectively. Both were associated with increasing age. H. pylori seropositivity was associated with higher odds of ANA (prevalence odds ratio = 1.89, 95% confidence interval = 1.08–3.33), adjusted for age, sex, race/ethnicity, educational attainment and body mass index. H. pylori infection may be one key factor in the loss of self-tolerance, contributing to immune dysfunction.
Coxiella burnetii, the causative agent of Q fever, is widely present in dairy products around the world. It has been isolated from unpasteurised milk and cheese and can survive for extended periods of time under typical storage conditions for these products. Although consumption of contaminated dairy products has been suggested as a potential route for transmission, it remains controversial. Given the high prevalence of C. burnetii in dairy products, we sought to examine the feasibility of transmitting the major sequence types (ST16, ST8 and ST20) of C. burnetii circulating in the United States. We delivered three strains of C. burnetii, comprising each sequence type, directly into the stomachs of immunocompetent BALB/c mice via oral gavage (OG) and assessed them for clinical symptoms, serological response and bacterial dissemination. We found that mice receiving C. burnetii by OG had notable splenomegaly only after infection with ST16. A robust immune response and persistence in the stomach and mesenteric lymph nodes were observed in mice receiving ST16 and ST20 by OG, and dissemination of C. burnetii to peripheral tissues was observed in all OG infected mice. These findings support the oral route as a mode of transmission for C. burnetii.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Introduction: Abdominal pain is one of the most frequent reasons for an emergency department (ED) visit. Most cases are functional and no therapy has proven effective. Our objective was to determine if hyoscine butylbromide (HBB) (BuscopanTM) is effective for children who present to the ED with functional abdominal pain. Methods: We conducted a randomized, blinded, superiority trial comparing HBB 10 mg plus acetaminophen placebo to oral acetaminophen 15 mg/kg (max 975 mg) plus HBB placebo using a double-dummy approach. We included children 8-17 years presenting to the ED at London Health Sciences Centre with colicky abdominal pain rated >40 mm on a 100 mm visual analog scale (VAS). The primary outcome was VAS pain score at 80 minutes post-administration. Secondary outcomes included adverse effects; caregiver satisfaction with pain management using a five-item Likert scale; recidivism and missed surgical diagnoses within 24-hours of discharge. Analysis was based on intention to treat. Results: We analyzed 225 participants (112 acetaminophen; 113 HBB). The mean (SD) age was 12.4 (3.0) years and 148/225 (65.8%) were females. Prior to enrollment, the median (IQR) duration of pain prior was 2 (4.5) hours and analgesia was provided to 101/225 (44.9%) of participants. The mean (SD) pre-intervention pain scores in the acetaminophen and HBB groups were 62.7 (15.9) mm and 60.3 (17.3) mm, respectively. At 80 minutes, the mean (SD) pain scores in the acetaminophen and HBB groups were 30.1 (28.8) mm and 29.4 (26.4) mm, respectively and there were no significant differences adjusting for pre-intervention scores (p = 0.96). The median (IQR) caregiver satisfaction was high in the acetaminophen [5 (2)] and HBB [5 (1)] groups (p = 0.79). The median (IQR) length of stay between acetaminophen [235 (101)] and HBB [234 (103)] was not significantly different (p = 0.53). The proportion of participants with a return visit for abdominal pain was 4/112 (3.5%) in the acetaminophen group and 6/113 (5.3%) in the HBB group. The most common adverse effect was nausea (9% in each group) and there were no significant differences in adverse effects between acetaminophen (26/112, 23.2%) and HBB (31/113, 27.4%) (p = 0.52). There were no missed surgical diagnoses. Conclusion: For children with presumed functional abdominal pain who present to the ED, both acetaminophen and HBB produce a clinically important (VAS < 30 mm) reduction in pain and should be routinely considered in this clinical setting.
Large efforts have been deployed in developing methods to estimate methane emissions from cattle. For large scale applications, accurate and inexpensive methane predictors are required. Within a livestock precision farming context, the objective of this work was to integrate real-time data on animal feeding behaviour with an in silico model for predicting the individual dynamic pattern of methane emission in cattle. The integration of real-time data with a mathematical model to predict variables that are not directly measured constitutes a software sensor. We developed a dynamic parsimonious grey-box model that uses as predictor variables either dry matter intake (DMI) or the intake time (IT). The model is described by ordinary differential equations.
Model building was supported by experimental data of methane emissions from respiration chambers. The data set comes from a study with finishing beef steers (cross-bred Charolais and purebred Luing finishing). Dry matter intake and IT were recorded using feed bins. For research purposes, in this work, our software sensor operated off-line. That is, the predictor variables (DMI, IT) were extracted from the recorded data (rather than from an on-line sensor). A total of 37 individual dynamic patterns of methane production were analyzed. Model performance was assessed by concordance analysis between the predicted methane output and the methane measured in respiration chambers. The model predictors DMI and IT performed similarly with a Lin’s concordance correlation coefficient (CCC) of 0.78 on average. When predicting the daily methane production, the CCC was 0.99 for both DMI and IT predictors. Consequently, on the basis of concordance analysis, our model performs very well compared with reported literature results for methane proxies and predictive models. As IT measurements are easier to obtain than DMI measurements, this study suggests that a software sensor that integrates our in silico model with a real-time sensor providing accurate IT measurements is a viable solution for predicting methane output in a large scale context.
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Understanding how critical sow live-weight and back-fat depth during gestation are in ensuring optimum sow productivity is important. The objective of this study was to quantify the association between sow parity, live-weight and back-fat depth during gestation with subsequent sow reproductive performance. Records of 1058 sows and 13 827 piglets from 10 trials on two research farms between the years 2005 and 2015 were analysed. Sows ranged from parity 1 to 6 with the number of sows per parity distributed as follows: 232, 277, 180, 131, 132 and 106, respectively. Variables that were analysed included total born (TB), born alive (BA), piglet birth weight (BtWT), pre-weaning mortality (PWM), piglet wean weight (WnWT), number of piglets weaned (Wn), wean to service interval (WSI), piglets born alive in subsequent farrowing and sow lactation feed intake. Calculated variables included the within-litter CV in birth weight (LtV), pre-weaning growth rate per litter (PWG), total litter gain (TLG), lactation efficiency and litter size reared after cross-fostering. Data were analysed using linear mixed models accounting for covariance among records. Third and fourth parity sows had more (P<0.05) TB, BA and heavier BtWT compared with gilts and parity 6 sow contemporaries. Parities 2 and 3 sows weaned more (P<0.05) piglets than older sows. These piglets had heavier (P<0.05) birth weights than those from gilt litters. LtV and PWM were greater (P<0.01) in litters born to parity 5 sows than those born to younger sows. Sow live-weight and back-fat depth at service, days 25 and 50 of gestation were not associated with TB, BA, BtWT, LtV, PWG, WnWT or lactation efficiency (P>0.05). Heavier sow live-weight throughout gestation was associated with an increase in PWM (P<0.01) and reduced Wn and lactation feed intake (P<0.05). Deeper back-fat in late gestation was associated with fewer (P<0.05) BA but heavier (P<0.05) BtWT, whereas deeper back-fat depth throughout gestation was associated with reduced (P<0.01) lactation feed intake. Sow back-fat depth was not associated with LtV, PWG, TLG, WSI or piglets born alive in subsequent farrowing (P>0.05). In conclusion, this study showed that sow parity, live-weight and back-fat depth can be used as indicators of reproductive performance. In addition, this study also provides validation for future development of a benchmarking tool to monitor and improve the productivity of modern sow herd.
Background: Serine deficiency disorders can result from deficiency in one of three enzymes. Deficiency of the second enzyme in the serine biosynthesis pathway, 3-phosphoserine aminotransferase (PSAT), has been reported in two siblings when the eldest was investigated for acquired microcephaly, progressive spasticity and intractable epilepsy. Methods: Our patient had neurological symptoms apparent at birth. Fetal magnetic resonance imaging (MRI) at 35 weeks gestation demonstrated microencephaly and simplification of the the gyration (anterior>posterior) which was confirmed upon subsequent post-natal MRI. Congenital microcephaly was apparent at birth. Results: PSAT deficiency was confirmed when exome sequencing identified biallelic mutations in PSAT1; c.44C>T, p.Ala15Val and; c.432delA, p.Pro144fs and biochemical testing noted low plasma serine 22 mcmol/L (normal 83-212 mcmol/L) and low CSF serine 10 mcmol/L (normal 22-61 mcmol/L). Despite oral serine and glycine supplementation at 4 months old the patient showed little neurodevelopmental progress and developed epileptic spasms at 10 months old. Serological testing for TORCH infections was negative. Conclusions: PSAT deficiency should be considered for patients with congenital microcephaly. Although further characterization of MRI findings in other patients is required, microencephaly with simplified gyral pattern could provide imaging clues for this rare metabolic disorder.
To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate
Prospective cohort study
US multicenter, quality-improvement, BSI prevention network
PHO centers across the United States who agreed to follow a standardized central-line–maintenance care bundle and track all BSI events and central-line days every month.
Infections were categorized as CLABSI (stratified by mucosal barrier injury–related, laboratory-confirmed BSI [MBI-LCBI] versus non–MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked.
Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates.
Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public.
The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
Vancomycin-resistant enterococci (VRE) infections are a public health threat associated with increased patient mortality and healthcare costs. Antibiotic usage, particularly cephalosporins, has been associated with VRE colonization and VRE bloodstream infections (VRE BSI). We examined the relationship between antimicrobial usage and incident VRE colonization at the individual patient level. Prospective, weekly surveillance was undertaken for incident VRE colonization defined by negative admission but positive surveillance swab in a medical intensive care unit over a 17-month period. Antimicrobial exposure was quantified as days of therapy (DOT)/1000 patient-days. Multiple logistic regression was used to analyse incident VRE colonization and antibiotic DOT, controlling for demographic and clinical covariates. Ninety-six percent (1398/1454) of admissions were swabbed within 24 h of intensive care unit (ICU) arrival and of the 380 patients in the ICU long enough for weekly surveillance, 83 (22%) developed incident VRE colonization. Incident colonization was associated in bivariate analysis with male gender, more previous hospital admissions, longer previous hospital stay, and use of cefepime/ceftazidime, fluconazole, azithromycin, and metronidazole (P < 0·05). After controlling for demographic and clinical covariates, metronidazole was the only antibiotic independently associated with incident VRE colonization (odds ratio 2·0, 95% confidence interval 1·2–3·3, P < 0·009). Our findings suggest that risk of incident VRE colonization differs between individual antibiotic agents and support the possibility that antimicrobial stewardship may impact VRE colonization and infection.
Antibiotic treatment for asymptomatic bacteriuria (ASB) is prevalent but often contrary to published guidelines.
To evaluate risk factors for treatment of ASB.
Retrospective observational study.
A tertiary academic hospital, county hospital, and community hospital.
Hospitalized adults with bacteriuria.
Patients without documented symptoms of urinary tract infection per Infectious Diseases Society of America (IDSA) criteria were classified as ASB. We examined ASB treatment risk factors as well as broad-spectrum antibiotic usage and quantified diagnostic concordance between IDSA and National Healthcare Safety Network criteria.
Among 300 patients with bacteriuria, ASB was present in 71% by IDSA criteria. By National Healthcare Safety Network criteria, 71% of patients had ASB; within-patient diagnostic concordance with IDSA was moderate (kappa, 0.52). After excluding those given antibiotics for nonurinary indications, antibiotics were given to 38% (62/164) with ASB. Factors significantly associated with ASB treatment were elevated urine white cell count (65 vs 24 white blood cells per high-powered field, P<.01), hospital identity (hospital C vs A, odds ratio, 0.34 [95% CI, 0.14–0.80], P =.01), presence of leukocyte esterase (5.48 [2.35–12.79], P<.01), presence of nitrites (2.45 [1.11–5.41], P=.03), and Escherichia coli on culture (2.4 [1.2–4.7], P=.01). Of patients treated for ASB, broad-spectrum antibiotics were used in 84%.
ASB treatment was prevalent across settings and contributed to broad-spectrum antibiotic use. Associating abnormal urinalysis results with the need for antibiotic treatment regardless of symptoms may drive unnecessary antibiotic use.
Infect. Control Hosp. Epidemiol. 2016;37(3):319–326
In North America, terrestrial records of biodiversity and climate change that span Marine Oxygen Isotope Stage (MIS) 5 are rare. Where found, they provide insight into how the coupling of the ocean–atmosphere system is manifested in biotic and environmental records and how the biosphere responds to climate change. In 2010–2011, construction at Ziegler Reservoir near Snowmass Village, Colorado (USA) revealed a nearly continuous, lacustrine/wetland sedimentary sequence that preserved evidence of past plant communities between ~140 and 55 ka, including all of MIS 5. At an elevation of 2705 m, the Ziegler Reservoir fossil site also contained thousands of well-preserved bones of late Pleistocene megafauna, including mastodons, mammoths, ground sloths, horses, camels, deer, bison, black bear, coyotes, and bighorn sheep. In addition, the site contained more than 26,000 bones from at least 30 species of small animals including salamanders, otters, muskrats, minks, rabbits, beavers, frogs, lizards, snakes, fish, and birds. The combination of macro- and micro-vertebrates, invertebrates, terrestrial and aquatic plant macrofossils, a detailed pollen record, and a robust, directly dated stratigraphic framework shows that high-elevation ecosystems in the Rocky Mountains of Colorado are climatically sensitive and varied dramatically throughout MIS 5.
Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i) Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access to Antarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.
Taxometric procedures, model-based clustering and latent variable mixture modeling (LVMM) are statistical methods that use the inter-relationships of observed symptoms or questionnaire items to investigate empirically whether the underlying psychiatric or psychological construct is dimensional or categorical. In this review we show why the results of such an investigation depend on the characteristics of the observed symptoms (e.g. symptom prevalence in the sample) and of the sample (e.g. clinical, population sample). Furthermore, the three methods differ with respect to their assumptions and therefore require different types of a priori knowledge about the observed symptoms and their inter-relationships. We argue that the choice of method should optimally match and make use of the existing knowledge about the data that are analyzed.