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A hospital water system colonized with Legionella bacteria (three of four buildings, with > 50% of positive samples) was able to reduce detections to <1% positivity in the long term only after ClO2 was iteratively added first to the cold-water and then hot-water systems followed by pipe replacements (n = 6835 total samples).
In functional magnetic resonance imaging (fMRI), the blood oxygenation level dependent (BOLD) signal is often interpreted as a measure of neural activity. However, because the BOLD signal reflects the complex interplay of neural, vascular, and metabolic processes, such an interpretation is not always valid. There is growing evidence that changes in the baseline neurovascular state can result in significant modulations of the BOLD signal that are independent of changes in neural activity. This paper introduces some of the normalization and calibration methods that have been proposed for making the BOLD signal a more accurate reflection of underlying brain activity for human fMRI studies.
Functional magnetic resonance imaging (fMRI) is a noninvasive method for measuring brain function by correlating temporal changes in local cerebral blood oxygenation with behavioral measures. fMRI is used to study individuals at single time points, across multiple time points (with or without intervention), as well as to examine the variation of brain function across normal and ill populations. fMRI may be collected at multiple sites and then pooled into a single analysis. This paper describes how fMRI data is analyzed at each of these levels and describes the noise sources introduced at each level.
Most students in MD-PhD programs take a leave of absence from medical school to complete PhD training, which promotes a natural loss of clinical skills and knowledge and could negatively impact a student’s long-term clinical knowledge. To address this concern, clinical refresher courses in the final year of PhD training have traditionally been used; however, effectiveness of such courses versus a longitudinal clinical course spanning all PhD training years is unclear.
Methods:
The University of Alabama at Birmingham MD-PhD Program implemented a comprehensive continuing clinical education (CCE) course spanning PhD training years that features three course components: (1) clinical skills; (2) clinical knowledge; and (3) specialty exposure activities. To evaluate course effectiveness, data from an anonymous student survey completed at the end of each semester were analyzed.
Results:
Five hundred and ninety-seven surveys were completed by MD-PhD students from fall 2014 to 2022. Survey responses indicated that the majority of students found the course helpful to: maintain clinical skills and knowledge (544/597, 91% and 559/597, 94%; respectively), gain exposure to clinical specialties (568/597, 95%), and prepare them for responsibilities during clinical clerkships. During semesters following lockdowns from the COVID-19 pandemic, there were significant drops in students’ perceived preparedness.
Conclusions:
Positive student survey feedback and improved preparedness to return to clinic after development of the course suggests the CCE course is a useful approach to maintain clinical knowledge during research training.
The U.S. Department of Agriculture–Agricultural Research Service (USDA-ARS) has been a leader in weed science research covering topics ranging from the development and use of integrated weed management (IWM) tactics to basic mechanistic studies, including biotic resistance of desirable plant communities and herbicide resistance. ARS weed scientists have worked in agricultural and natural ecosystems, including agronomic and horticultural crops, pastures, forests, wild lands, aquatic habitats, wetlands, and riparian areas. Through strong partnerships with academia, state agencies, private industry, and numerous federal programs, ARS weed scientists have made contributions to discoveries in the newest fields of robotics and genetics, as well as the traditional and fundamental subjects of weed–crop competition and physiology and integration of weed control tactics and practices. Weed science at ARS is often overshadowed by other research topics; thus, few are aware of the long history of ARS weed science and its important contributions. This review is the result of a symposium held at the Weed Science Society of America’s 62nd Annual Meeting in 2022 that included 10 separate presentations in a virtual Weed Science Webinar Series. The overarching themes of management tactics (IWM, biological control, and automation), basic mechanisms (competition, invasive plant genetics, and herbicide resistance), and ecosystem impacts (invasive plant spread, climate change, conservation, and restoration) represent core ARS weed science research that is dynamic and efficacious and has been a significant component of the agency’s national and international efforts. This review highlights current studies and future directions that exemplify the science and collaborative relationships both within and outside ARS. Given the constraints of weeds and invasive plants on all aspects of food, feed, and fiber systems, there is an acknowledged need to face new challenges, including agriculture and natural resources sustainability, economic resilience and reliability, and societal health and well-being.
The severity of respiratory distress occurring prior to loss of posture during exposure to: 20, 30, 40, 50, 60, 70, 80 or 90 per cent carbon dioxide in air; 2 or 5 per cent residual oxygen in argon; 30 per cent carbon dioxide in argon with either 2 or 5 per cent residual oxygen; or 40 per cent carbon dioxide in argon with either 2 or 5 per cent residual oxygen, was subjectively determined in pigs from their behaviour. The results indicated that exposure to 2 per cent oxygen in argon (anoxia) induced minimal respiratory distress, 30 per cent carbon dioxide in argon with 2 per cent residual oxygen induced a moderate distress and exposure to all the concentrations of carbon dioxide in air induced severe respiratory distress in the pigs. From the animal welfare point of view, using 2 per cent oxygen in argon (anoxia) appears to be the optimum choice for gas stunning pigs. Secondly, a mixture of 30 per cent carbon dioxide in argon with 2 per cent residual oxygen is preferred to 90 per cent carbon dioxide in air.
The aversive effects of 90 per cent argon in air, 30 per cent carbon dioxide in air or 90 per cent carbon dioxide in air were investigated in slaughter weight pigs. Aversion was assessed from their reluctance to enter the three gaseous atmospheres to obtain a reward (apples). The pigs did not show any aversion to the inhalation of 90 per cent argon in air. The majority of the pigs did not show aversion to the presence of 30 per cent carbon dioxide in air. By contrast, the inhalation of 90 per cent carbon dioxide was aversive to the majority of the pigs. Fasting them for up to 24h prior to testing did not overcome the pigs ‘ reluctance to enter an atmosphere containing 90 per cent carbon dioxide.
Deflighting is used to prevent large captive birds from escaping by limiting their ability to fly. This practice deprives birds of this normal behaviour, but can allow them to express other behaviours that would be suppressed if they were confined to cages or aviaries. The potential negative welfare issues associated with deflighting include the stress of capture and restraint, pain and discomfort associated with the procedure and during recovery, risk of post-operative infections, risk of neuroma formation which could lead to pain, and loss of the ability to fly. The potential practical and welfare advantages of deflighting include a reduction in the need to closely confine or cage birds to prevent them from escaping, and deflighting may be the only way of keeping particular birds in an open situation for display, such as in parks or zoos. In these respects, there must be a balance between the requirement for this practice and the welfare compromises it introduces for birds. By outlining temporary and permanent methods and the complications involved, the following review highlights potential welfare problems and discusses ways of avoiding them. It also evaluates the necessity of deflighting and the need for careful risk assessment.
Disease is one of the most important causes of animal suffering. When diseases are treated the aim is to achieve rapid and permanent recovery and this helps to reduce the duration of suffering. It does not, however, alleviate suffering during the fulminant and recovery phases. Greater attention needs to be given to alleviating suffering and the signs of sickness during disease states. In this paper, the role of the cytokines in mediating sickness behaviour and suffering during disease is reviewed. The importance of sickness behaviour in improving the chances of recovery are considered, along with the potential use of anti-cytokine strategies in alleviating suffering in disease states.
This study examined struggles to establish autonomy and relatedness with peers in adolescence and early adulthood as predictors of advanced epigenetic aging assessed at age 30. Participants (N = 154; 67 male and 87 female) were observed repeatedly, along with close friends and romantic partners, from ages 13 through 29. Observed difficulty establishing close friendships characterized by mutual autonomy and relatedness from ages 13 to 18, an interview-assessed attachment state of mind lacking autonomy and valuing of attachment at 24, and self-reported difficulties in social integration across adolescence and adulthood were all linked to greater epigenetic age at 30, after accounting for chronological age, gender, race, and income. Analyses assessing the unique and combined effects of these factors, along with lifetime history of cigarette smoking, indicated that each of these factors, except for adult social integration, contributed uniquely to explaining epigenetic age acceleration. Results are interpreted as evidence that the adolescent preoccupation with peer relationships may be highly functional given the relevance of such relationships to long-term physical outcomes.
Myelomeningocele (MMC), the most common congenital abnormality of the central nervous system (CNS), occurs due to failure of the neural tube to close in the first 4 weeks after conception and is characterized by a fluid-filled sac containing an exposed spinal cord and nerves. Myeloschisis is similar to MMC except that a membranous sac is not present and the defect is wider (Figure 44.1). The consequence of an open neural tube defect is abnormal development of the CNS. The neural elements become damaged from exposure to the toxic effects of amniotic fluid, leading to associated long-term morbidity and mortality. Cerebrospinal fluid (CSF) leaks out through the MMC and as a consequence the hindbrain herniates into the cervical spinal canal and blocks CSF circulation, leading to hydrocephalus and brain damage. Although 75% of individuals affected with spina bifida survive to adulthood, the one-year survival rate for infants is 88–96% [1, 2]. More than 80% of affected individuals require a ventriculo-peritoneal shunt to divert CSF in order to decompress the associated hydrocephalus, and this is dependent upon lesion level, with the need being greater for those with higher level lesions [3]. The need for a shunt is associated with complications including infection, obstruction, displacement, and shunt revisions [3, 4]. More than 75% of patients have radiographic evidence of the Chiari II malformation (hindbrain herniation, brain stem abnormalities, and a small posterior fossa) that can manifest clinically as apnea, swallowing difficulties, quadriparesis, and coordination difficulties in up to one-third of affected individuals [5–7]. Functional motor levels correlate with lesion level in approximately 39% of patients, but in over half the functional level correlates to anatomic lesions two levels higher [3]. Wheelchair use correlates with lesion level; 90% of patients with a thoracic lesion use a wheelchair while 45% with a lumbar lesion and 17% with a sacral lesion use a wheelchair [8]. Bladder and bowel incontinence are also associated with MMC, necessitating the use of bowel and bladder regimens including clean intermittent catheterization and enemas. Urologic complications include recurrent urinary tract infections, vesicoureteral reflux, and upper urinary tract dilation [9]. Additionally, the overwhelming majority of infants will require intervention for a foot deformity [10]. For those living long term with spina bifida, up to one-third of adults require daily assistance and a high rate of unexpected death has been noted [11, 12].
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.
Methods
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
Results
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).
Conclusions
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
The physics of compressible turbulence in high energy density (HED) plasmas is an unchartered experimental area. Simulations of compressible and radiative flows relevant for astrophysics rely mainly on subscale parameters. Therefore, we plan to perform turbulent hydrodynamics experiments in HED plasmas (TurboHEDP) in order to improve our understanding of such important phenomena for interest in both communities: laser plasma physics and astrophysics. We will focus on the physics of supernovae remnants which are complex structures subject to fluid instabilities such as the Rayleigh–Taylor and Kelvin–Helmholtz instabilities. The advent of megajoule laser facilities, like the National Ignition Facility and the Laser Megajoule, creates novel opportunities in laboratory astrophysics, as it provides unique platforms to study turbulent mixing flows in HED plasmas. Indeed, the physics requires accelerating targets over larger distances and longer time periods than previously achieved. In a preparatory phase, scaling from experiments at lower laser energies is used to guarantee the performance of future MJ experiments. This subscale experiments allow us to develop experimental skills and numerical tools in this new field of research, and are stepping stones to achieve our objectives on larger laser facilities. We review first in this paper recent advances in high energy density experiments devoted to laboratory astrophysics. Then we describe the necessary steps forward to commission an experimental platform devoted to turbulent hydrodynamics on a megajoule laser facility. Recent novel experimental results acquired on LULI2000, as well as supporting radiative hydrodynamics simulations, are presented. Together with the development of LiF detectors as transformative X-ray diagnostics, these preliminary results are promising on the way to achieve micrometric spatial resolution in turbulent HED physics experiments in the near future.
The influence of a strong external magnetic field on the collimation of a high Mach number plasma flow and its collision with a solid obstacle is investigated experimentally and numerically. The laser irradiation ($I\sim 2\times 10^{14}~\text{W}\cdot \text{cm}^{-2}$) of a multilayer target generates a shock wave that produces a rear side plasma expanding flow. Immersed in a homogeneous 10 T external magnetic field, this plasma flow propagates in vacuum and impacts an obstacle located a few mm from the main target. A reverse shock is then formed with typical velocities of the order of 15–20 $\pm$ 5 km/s. The experimental results are compared with 2D radiative magnetohydrodynamic simulations using the FLASH code. This platform allows investigating the dynamics of reverse shock, mimicking the processes occurring in a cataclysmic variable of polar type.
In this paper, we present a model characterizing the interaction of a radiative shock (RS) with a solid material, as described in a recent paper (Koenig et al., Phys. Plasmas, 24, 082707 (2017)), the new model is then related to recent experiments performed on the GEKKO XII laser facility. The RS generated in a xenon gas cell propagates towards a solid obstacle that is ablated by radiation coming from the shock front and the radiative precursor, mimicking processes occurring in astrophysical phenomena. The model presented here calculates the dynamics of the obstacle expansion, which depends on several parameters, notably the geometry and the temperature of the shock. All parameters required for the model have been obtained from experiments. Good agreement between experimental data and the model is found when spherical geometry is taken into account. As a consequence, this model is a useful and easy tool to infer parameters from experimental data (such as the shock temperature), and also to design future experiments.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
The evolution of glyphosate resistance in weedy species places an environmentally benign herbicide in peril. The first report of a dicot plant with evolved glyphosate resistance was horseweed, which occurred in 2001. Since then, several species have evolved glyphosate resistance and genomic information about nontarget resistance mechanisms in any of them ranges from none to little. Here, we report a study combining iGentifier transcriptome analysis, cDNA sequencing, and a heterologous microarray analysis to explore potential molecular and transcriptomic mechanisms of nontarget glyphosate resistance of horseweed. The results indicate that similar molecular mechanisms might exist for nontarget herbicide resistance across multiple resistant plants from different locations, even though resistance among these resistant plants likely evolved independently and available evidence suggests resistance has evolved at least four separate times. In addition, both the microarray and sequence analyses identified non–target-site resistance candidate genes for follow-on functional genomics analysis.
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.