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.
Tick-borne diseases (TBDs) can sometimes cause severe symptoms and lead to hospitalisation, but they often go unnoticed in the Emergency Department (ED). The aim of this study was twofold: (i) to describe the profile of patients hospitalised by TBDs; and (ii) to evaluate the data collected in the medical records from the ED in order to analyse their potential clinical consequences. A total of 84 cases that included all TBD diagnoses registered in the ED records were identified and analysed. These corresponded to all the hospitalisations by TBDs in the last 10 years (2009–2019) in two tertiary hospitals in Granada, Spain. Statistical analyses were made using RStudio. Coinciding with the absence of patient's report of exposure to ticks, 64.3% of TBDs were not suspected in the ED. Intensive care unit admission was required in 8.3% of cases, and the mortality rate was 2.4%. Non-suspected cases showed longer hospital stay (P < 0.001), treatment duration (P = 0.02) and delay in the initiation of antibiotic treatment (P < 0.001). Our findings indicate that symptoms associated with TBDs are highly non-specific. In the absence of explicit information related to potential tick exposure, TBDs are not initially suspected. As a consequence, elective treatment administration is delayed and hospitalisation time is prolonged. In conclusion, our results highlight the importance of addressing potential exposure to ticks during the ED contact with patients presenting with febrile syndrome.
In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Microstructural analysis and bulk dielectric property analysis (real and imaginary permittivity at 95 GHz) were performed at temperatures ranging from 25 to 550 °C for ceramic composites comprising a hot-pressed aluminum nitride matrix (containing yttria and trace carbon as sintering additives) with molybdenum powder as a millimeter-wave radiation-absorbing additive. Loading percentages in the range of 0.25 vol% to 4.0 vol% Mo were characterized. For the temperature regime evaluated, the temperature-related changes in real and imaginary components of permittivity were found to be relatively modest compared with those driven by Mo loading. Energy-dispersive X-ray spectroscopic analysis of Mo grains and surrounding regions showed the presence of a mixed-phase layer, containing Mo2C, at the AlN–Mo interface. The Mo2C-containing mixed-phase layer, typically a few micrometers thick, surrounded the Mo grains. Further characterization of this mixed-phase layer is required to determine its contribution to the dielectric properties of the composite.
To sustainably improve cleaning of high-touch surfaces (HTSs) in acute-care hospitals using a multimodal approach to education, reduction of barriers to cleaning, and culture change for environmental services workers.
The study was conducted in 2 academic acute-care hospitals, 2 community hospitals, and an academic pediatric and women’s hospital.
Frontline environmental services workers.
A 5-module educational program, using principles of adult learning theory, was developed and presented to environmental services workers. Audience response system (ARS), videos, demonstrations, role playing, and graphics were used to illustrate concepts of and the rationale for infection prevention strategies. Topics included hand hygiene, isolation precautions, personal protective equipment (PPE), cleaning protocols, and strategies to overcome barriers. Program evaluation included ARS questions, written evaluations, and objective assessments of occupied patient room cleaning. Changes in hospital-onset C. difficile infection (CDI) and methicillin-resistant S. aureus (MRSA) bacteremia were evaluated.
On average, 357 environmental service workers participated in each module. Most (93%) rated the presentations as ‘excellent’ or ‘very good’ and agreed that they were useful (95%), reported that they were more comfortable donning/doffing PPE (91%) and performing hand hygiene (96%) and better understood the importance of disinfecting HTSs (96%) after the program. The frequency of cleaning individual HTSs in occupied rooms increased from 26% to 62% (P < .001) following the intervention. Improvement was sustained 1-year post intervention (P < .001). A significant decrease in CDI was associated with the program.
A novel program that addressed environmental services workers’ knowledge gaps, challenges, and barriers was well received and appeared to result in learning, behavior change, and sustained improvements in cleaning.
Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.
There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.
The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20–39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range = 22–44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep–wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions.
Innovation Concept: Competence by Design (CBD) was implemented nationally for Emergency Medicine (EM) residents beginning training in 2018. One challenge is the need to introduce residents to Entrustable Professional Activities (EPAs) that are assessed across numerous clinical rotations. The Royal College's resources detail these requirements, but do not map them to specific rotations or present them in a succinct format. This is problematic as trainees are less likely to succeed when expectations are unclear. We identified a need to create practical resources that residents can use at the bedside. Methods: We followed an intervention mapping framework to design two practical, user-friendly, low-cost, aesthetically pleasing resources that could be used by residents and observers at the bedside to facilitate competency-based assessment. Curriculum, Tool or Material: First, we designed a set of rotation- and stage-specific EPA reference cards for the use of residents and observers at the bedside. These cards list EPAs and clinical presentations likely to be encountered during various stages of training and on certain rotations. Second, we developed a curriculum board to organize the EPA reference cards by stage based upon our program's curriculum map. The curriculum board allows residents to view the program's curriculum map and the EPAs associated with each clinical rotation at a glance. It also contains hooks to hang and store extra cards in an organized manner. Conclusion: We believe that these practical and inexpensive tools facilitated our residency program's transition to competency-based EPA assessments. Anecdotally, the residents are using the cards and completing the suggested rotation-specific EPAs. We hope that the reference cards and curriculum board will be successfully incorporated into other residency programs to facilitate the introduction of their EPA-based CBD assessment system.
Herbicides registered in vegetable soybean often fail to control waterhemp. The objective of this research was to quantify vegetable soybean tolerance to preemergence herbicides for early-season waterhemp control, including flumioxazin applied alone PRE or in mixture with chlorimuron, metribuzin, or pyroxasulfone at use rates in grain-type soybean. Crop tolerance to the herbicides was tested in field trials with 20 vegetable soybean cultivars and four grain-type cultivars through 4 wk after treatment (WAT). Flumioxazin-based treatments were equally safe, resulting in only minor, transitory crop response (<5% injury 2 WAT) and no effect on crop emergence or early season growth. Flumioxazin mixtures provided greater than 99% control of waterhemp 4 WAT, as evidenced by reduced weed density from 29.7 plants m−2 in the nontreated control to no waterhemp. Flumioxazin applied alone or in tank mixture with chlorimuron, metribuzin, or pyroxasulfone were as safe in vegetable soybean as previously reported in grain-type soybean. Registration of these products in vegetable soybean would provide the industry with additional options for managing waterhemp.
In order to begin to evaluate and model the suitability of high temperature ceramic composites, such as AlN:Mo, as susceptor materials for power beaming applications, the electromagnetic, thermal, and mechanical properties of the material must be known at elevated temperatures. Work reported here focuses on the development of thermal property datasets for AlN:Mo composites ranging from 0.25% to 4.0% Mo by volume. To calculate thermal conductivity of the AlN:Mo composite series, specific heat capacity, thermal diffusivity, and density data were acquired. The calculated specific heat capacity, Cp, of the set of AlN:Mo composites was, on average, found to be approximately 803 J/kgK at 100 °C and to increase to approximately 1133 J/kgK at 1000 °C, with all values to be within +/- 32 J/kgK of the average at a given temperature. These calculated specific heat capacity values matched values derived from DSC measurements to within the expected error of the measurements. Measured thermal diffusivity, α, of the set of AlN:Mo composites was, on average, found to be approximately 3.93 x 10-1 cm2/s at 100 °C and to increase to approximately 9.80 x 10-2 cm2/s at 1000 °C, with all values within +/- 1.84 x 10-2 cm2/s of the average at a given temperature. Thermal conductivity, k, for the set of AlN:Mo composites was found to be approximately 108 W/mK at 100 °C and to decrease to approximately 38 W/mK at 1000 °C, with all values within +/- 5.3 W/mK of the average at a given temperature. Data trends show that increasing Mo content correlates to lower values of of Cp, α, and k at a given temperature.
Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.
OBJECTIVES/SPECIFIC AIMS: Rodent models can be used to study neonatal abstinence syndrome (NAS), but the applicability of findings from the models to NAS in humans is not well understood. The objective of this study was to develop a rat model of norbuprenorphine-induced NAS and validate its translational value by comparing blood concentrations in the norbuprenorphine-treated pregnant rat to those previously reported in pregnant women undergoing buprenorphine treatment. METHODS/STUDY POPULATION: Pregnant Long-Evans rats were implanted with 14-day osmotic minipumps containing vehicle, morphine (positive control), or norbuprenorphine (0.3–3 mg/kg/d) on gestation day 9. Within 12 hours of delivery, pups were tested for spontaneous or precipitated opioid withdrawal by injecting them with saline (10 mL/kg, i.p.) or naltrexone (1 or 10 mg/kg, i.p), respectively, and observing them for well-validated neonatal withdrawal signs. Blood was sampled via indwelling jugular catheters from a subset of norbuprenorphine-treated dams on gestation day 8, 10, 13, 17, and 20. Norbuprenorphine concentrations in whole blood samples were quantified using LC/MS/MS. RESULTS/ANTICIPATED RESULTS: Blood concentrations of norbuprenorphine in rats exposed to 1–3 mg/kg/d of norbuprenorphine were similar to levels previously reported in pregnant women undergoing buprenorphine treatment. Pups born to dams treated with these doses exhibited robust withdrawal signs. Blood concentrations of norbuprenorphine decreased across gestation, which is similar to previous reports in humans. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that dosing dams with 1–3 mg/kg/day norbuprenorphine produces maternal blood concentrations and withdrawal severity similar to those previously reported in humans. This provides evidence that, at these doses, this model is useful for testing hypotheses about norbuprenorphine that are applicable to NAS in humans.
Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.
Collaborative programs have helped reduce catheter-associated urinary tract infection (CAUTI) rates in community-based nursing homes. We assessed whether collaborative participation produced similar benefits among Veterans Health Administration (VHA) nursing homes, which are part of an integrated system.
This study included 63 VHA nursing homes enrolled in the “AHRQ Safety Program for Long-Term Care,” which focused on practices to reduce CAUTI.
Changes in CAUTI rates, catheter utilization, and urine culture orders were assessed from June 2015 through May 2016. Multilevel mixed-effects negative binomial regression was used to derive incidence rate ratios (IRRs) representing changes over the 12-month program period.
There was no significant change in CAUTI among VHA sites, with a CAUTI rate of 2.26 per 1,000 catheter days at month 1 and a rate of 3.19 at month 12 (incidence rate ratio [IRR], 0.99; 95% confidence interval [CI], 0.67–1.44). Results were similar for catheter utilization rates, which were 11.02% at month 1 and 11.30% at month 12 (IRR, 1.02; 95% CI, 0.95–1.09). The numbers of urine cultures per 1,000 residents were 5.27 in month 1 and 5.31 in month 12 (IRR, 0.93; 95% CI, 0.82–1.05).
No changes in CAUTI rates, catheter use, or urine culture orders were found during the program period. One potential reason was the relatively low baseline CAUTI rate, as compared with a cohort of community-based nursing homes. This low baseline rate is likely related to the VHA’s prior CAUTI prevention efforts. While broad-scale collaborative approaches may be effective in some settings, targeting higher-prevalence safety issues may be warranted at sites already engaged in extensive infection prevention efforts.
Intensive farming may involve the use of diets, environments or management practices that impose physiological and psychological stressors on the animals. In particular, early weaning is nowadays a common practice to increase the productive yield of pig farms. Still, it is considered one of the most critical periods in swine production, where piglet performance can be seriously affected and where they are predisposed to the overgrowth of opportunistic pathogens. Pig producers nowadays face the challenge to overcome this situation in a context of increasing restrictions on the use of antibiotics in animal production. Great efforts are being made to find strategies to help piglets overcome the challenges of early weaning. Among them, a nutritional strategy that has received increasing attention in the last few years is the use of probiotics. It has been extensively documented that probiotics can reduce digestive disorders and improve productive parameters. Still, research in probiotics so far has also been characterized as being inconsistent and with low reproducibility from farm to farm. Scientific literature related to probiotic effects against gastrointestinal pathogens will be critically examined in this review. Moreover, the actual practical approach when using probiotics in these animals, and potential strategies to increase consistency in probiotic effects, will be discussed. Thus, considering the boost in probiotic research observed in recent years, this paper aims to provide a much-needed, in-depth review of the scientific data published to-date. Furthermore, it aims to be useful to swine nutritionists, researchers and the additive industry to critically consider their approach when developing or using probiotic strategies in weaning piglets.
A far-infrared observatory such as the SPace Infrared telescope for Cosmology and Astrophysics, with its unprecedented spectroscopic sensitivity, would unveil the role of feedback in galaxy evolution during the last ~10 Gyr of the Universe (z = 1.5–2), through the use of far- and mid-infrared molecular and ionic fine structure lines that trace outflowing and infalling gas. Outflowing gas is identified in the far-infrared through P-Cygni line shapes and absorption blueshifted wings in molecular lines with high dipolar moments, and through emission line wings of fine-structure lines of ionised gas. We quantify the detectability of galaxy-scale massive molecular and ionised outflows as a function of redshift in AGN-dominated, starburst-dominated, and main-sequence galaxies, explore the detectability of metal-rich inflows in the local Universe, and describe the most significant synergies with other current and future observatories that will measure feedback in galaxies via complementary tracers at other wavelengths.