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.
Quantitative plant biology is an interdisciplinary field that builds on a long history of biomathematics and biophysics. Today, thanks to high spatiotemporal resolution tools and computational modelling, it sets a new standard in plant science. Acquired data, whether molecular, geometric or mechanical, are quantified, statistically assessed and integrated at multiple scales and across fields. They feed testable predictions that, in turn, guide further experimental tests. Quantitative features such as variability, noise, robustness, delays or feedback loops are included to account for the inner dynamics of plants and their interactions with the environment. Here, we present the main features of this ongoing revolution, through new questions around signalling networks, tissue topology, shape plasticity, biomechanics, bioenergetics, ecology and engineering. In the end, quantitative plant biology allows us to question and better understand our interactions with plants. In turn, this field opens the door to transdisciplinary projects with the society, notably through citizen science.
To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care.
Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3–4, 6–8,<Vinod: Please carry out the deletion of serial commas throughout the article> and 9–12 months post-baseline and remission at 3–4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/.
There was no evidence of an association between age and prognosis before or after adjusting for depressive ‘disorder characteristics’ that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3–4 months post-baseline per-5-year increase in age = 0(95% CI: −0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3–4 months or 9–12 months post-baseline, but men had worse prognoses at 6–8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6–8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive ‘disorder characteristics’ and employment status (12.23% (−1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive ‘disorder characteristics’ and all available confounders.
Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive ‘disorder characteristics’ in clinic may be important.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
A single radiocarbon date derived from the Buhl burial in south-central Idaho has frequently been used as a data point for the interpretation of the Western Stemmed Tradition (WST) chronology and technology because of the stemmed biface found in situ with the human remains. AMS dating of bone collagen in 1991 produced an age of 10,675 ± 95 14C BP, immediately postdating the most widely accepted age range for Clovis. The Buhl burial has been cited as evidence that stemmed point technology may have overlapped with Clovis technology in the Intermountain West. We discuss concerns about the radiocarbon date, arguing that even at face value, the calibrated date has minimal overlap with Clovis at the 95.4% range. Furthermore, the C:N ratio of 3.69 in the analyzed collagen is outside of the typical range for well-preserved samples, indicating a postdepositional change in carbon composition, which may make the date erroneously older or younger than the age of the skeleton. Finally, the potential dietary incorporation of small amounts of anadromous fish may indicate that the burial is younger than traditionally accepted. For these reasons, we argue that the Buhl burial cannot be used as evidence of overlap between WST and Clovis.
OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.
OBJECTIVES/GOALS: Active surveillance (AS) is a recognized strategy to manage low-risk prostate cancer (PCa) in the absence of cancer progression. Little prospective data exists on the decisional factors associated with selecting and adhering to AS in the absence of cancer progression. We developed a survey instrument to predict AS uptake and adherence. METHODS/STUDY POPULATION: We utilized a three-step process to develop and refine a survey instrument designed to predict AS uptake and adherence among men with low-risk PCa: 1) We identified relevant conceptual domains based on prior research and a literature review. 2) We conducted 21 semi-structured concept elicitation interviews to identify patient-perceived barriers and facilitators to AS uptake and adherence among men with a low-risk PCa who had been on AS for ≥1 year. The identified concepts became the basis of our draft survey instrument. 3) We conducted two rounds of cognitive interviews with men with low-risk PCa (n = 12; n = 6) to refine and initially validate the instrument. RESULTS/ANTICIPATED RESULTS: Relevant concepts identified from the initial interviews included the importance of patient: knowledge of their PCa risk, value in delaying treatment, trust in urologist and the AS surveillance protocol, and perceived social support. Initially, the survey was drafted as a single instrument to be administered after a patient had selected AS comprising sections on patient health, AS selection, and AS adherence. Based on the first round of cognitive interviews, we revised the single instrument into two surveys to track shifts in patient preference and experience. The first, administered at diagnosis, focuses on selection, and the second, a 6-month follow up, focuses on adherence. Following revisions, participants indicated the revised 2-part instrument was clear and not burdensome to complete. DISCUSSION/SIGNIFICANCE OF IMPACT: The instrument’s content validity was evaluated through cognitive interviews, which supported that the survey items’ intended and understood meanings were isomorphic. In the next phase, we plan to conduct a large-scale prospective cohort study to evaluate the predictive validity, after which it will be available for public research use.
Internet-delivered treatments for depression have proved successful, with supported programs offering the potential for improved adherence and outcomes. Internet interventions are particularly interesting in the context of increasing access to interventions, and delivering interventions population-wide.
Investigate the potential feasibility and effectiveness of an online intervention for depression in the community.
Establish the effectiveness of a supported online delivered cognitive behavioural intervention for symptoms of depression in adults in the community.
The study was a randomized controlled trial of an 8-module internet-delivered cognitive behavioral therapy (iCBT) program for adults with depressive symptoms (n = 96) compared to a waiting-list control group (n = 92). Participants received weekly support from a trained supporter. The primary outcome was depressive symptoms as measured by the Beck Depression Inventory (BDI-II). The program was made available nationwide from an established and recognized charity for depression.
For the treatment group, post-treatment effect sizes reported were large for the primary outcome measure (d = 0.91). The between-group effects were moderate to large and statistically significant for the primary outcomes (d = 0.50) favoring the treatment group. Gains were maintained at 6-month follow-up.
The study has demonstrated the efficacy of the online delivered space from depression treatment. Participants demonstrated reliable and statistically significant changes in symptoms from pre- to post-intervention. The study supports a model for delivering online depression interventions population-wide using trained supporters.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada.
We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers.
Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT).
Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
Weight gain among psychiatric inpatients is a widespread phenomenon. This change in body mass index (BMI) can be caused by several factors. Based on recent research, we assume the following factors are related to weight gain during psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis, sex, age, weight on admission and geographic region of treatment.
876 of originally recruited 2328 patients met the criteria for our analysis. Patients were recruited and examined in mental health care centres in Nigeria (N=265), Japan (N=145) and Western-Europe (Denmark, Germany and Switzerland; N=466).
There was a significant effect of psychiatric medication, psychiatric diagnoses and geographic region, but not age and sex, on BMI changes. Geographic region had a significant effect on BMI change, with Nigerian patients gaining significantly more weight than Japanese and Western European patients. Moreover, geographic region influenced the type of psychiatric medication prescribed and the psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a significant effect on BMI change.
In conclusion, we consider weight gain as a multifactorial phenomenon that is influenced by several factors. One can discuss a number of explanations for our findings, such as different clinical practices in the geographical regions (prescribing or admission strategies and access-to-care aspects), as well as socio-economic and cultural differences.
Despite some improvements in access to evidence-based medications for opioid use disorder, treatment rates remain low at under a quarter of those with need. High costs for brand name products in these medication markets have limited the volume of drugs purchased, particularly through public health insurance and grant programs. Brand firm anti-competitive practices around the leading buprenorphine product Suboxone — including product hops, citizen petitions and Risk Evaluation and Mitigation Strategy abuses — helped to maintain high prices by extending brand exclusivity periods and hindering generic drug entry. Remedies to address costly anti-competitive activities include adoption of the proposed CREATES Act and modernization of the Hatch-Waxman Act by the Congress, and implementation of substantive modifications to the Food and Drug Administration citizen petition filing procedures. Given the persistence of these abuses, prescriptive changes are favorable to the procedural and clarifying steps thus far favored by the federal government. Extrapolating from the 37% price declines attributable to generic entry for buprenorphine tablets in 2011, our calculations suggest that implementing these remedies to facilitate generic competition with Suboxone film would have resulted in savings of approximately $703 million overall and $203 million to Medicaid in 2017.
In Canada, recreational use of cannabis was legalized in October 2018. This policy change along with recent publications evaluating the efficacy of cannabis for the medical treatment of epilepsy and media awareness about its use have increased the public interest about this agent. The Canadian League Against Epilepsy Medical Therapeutics Committee, along with a multidisciplinary group of experts and Canadian Epilepsy Alliance representatives, has developed a position statement about the use of medical cannabis for epilepsy. This article addresses the current Canadian legal framework, recent publications about its efficacy and safety profile, and our understanding of the clinical issues that should be considered when contemplating cannabis use for medical purposes.
Weed management is a major challenge in organic crop production, and organic farms generally harbor larger weed populations and more diverse communities compared with conventional farms. However, little research has been conducted on the effects of different organic management practices on weed communities and crop yields. In 2014 and 2015, we measured weed community structure and soybean [Glycine max (L.) Merr.] yield in a long-term experiment that compared four organic cropping systems that differed in nutrient inputs, tillage, and weed management intensity: (1) high fertility (HF), (2) low fertility (LF), (3) enhanced weed management (EWM), and (4) reduced tillage (RT). In addition, we created weed-free subplots within each system to assess the impact of weeds on soybean yield. Weed density was greater in the LF and RT systems compared with the EWM system, but weed biomass did not differ among systems. Weed species richness was greater in the RT system compared with the EWM system, and weed community composition differed between RT and other systems. Our results show that differences in weed community structure were primarily related to differences in tillage intensity, rather than nutrient inputs. Soybean yield was lower in the EWM system compared with the HF and RT systems. When averaged across all four cropping systems and both years, soybean yield in weed-free subplots was 10% greater than soybean yield in the ambient weed subplots that received standard management practices for the systems in which they were located. Although weed competition limited soybean yield across all systems, the EWM system, which had the lowest weed density, also had the lowest soybean yield. Future research should aim to overcome such trade-offs between weed control and yield potential, while conserving weed species richness and the ecosystem services associated with increased weed diversity.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
Immune system markers may predict affective disorder treatment response, but whether an overall immune system marker predicts bipolar disorder treatment effect is unclear.
Bipolar CHOICE (N = 482) and LiTMUS (N = 283) were similar comparative effectiveness trials treating patients with bipolar disorder for 24 weeks with four different treatment arms (standard-dose lithium, quetiapine, moderate-dose lithium plus optimised personalised treatment (OPT) and OPT without lithium). We performed secondary mixed effects linear regression analyses adjusted for age, gender, smoking and body mass index to investigate relationships between pre-treatment white blood cell (WBC) levels and clinical global impression scale (CGI) response.
Compared to participants with WBC counts of 4.5–10 × 109/l, participants with WBC < 4.5 or WBC ≥ 10 showed similar improvement within each specific treatment arm and in gender-stratified analyses.
An overall immune system marker did not predict differential treatment response to four different treatment approaches for bipolar disorder all lasting 24 weeks.
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.
Determining infectious cross-transmission events in healthcare settings involves manual surveillance of case clusters by infection control personnel, followed by strain typing of clinical/environmental isolates suspected in said clusters. Recent advances in genomic sequencing and cloud computing now allow for the rapid molecular typing of infecting isolates.
To facilitate rapid recognition of transmission clusters, we aimed to assess infection control surveillance using whole-genome sequencing (WGS) of microbial pathogens to identify cross-transmission events for epidemiologic review.
Clinical isolates of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Klebsiella pneumoniae were obtained prospectively at an academic medical center, from September 1, 2016, to September 30, 2017. Isolate genomes were sequenced, followed by single-nucleotide variant analysis; a cloud-computing platform was used for whole-genome sequence analysis and cluster identification.
Most strains of the 4 studied pathogens were unrelated, and 34 potential transmission clusters were present. The characteristics of the potential clusters were complex and likely not identifiable by traditional surveillance alone. Notably, only 1 cluster had been suspected by routine manual surveillance.
Our work supports the assertion that integration of genomic and clinical epidemiologic data can augment infection control surveillance for both the identification of cross-transmission events and the inclusion of missed and exclusion of misidentified outbreaks (ie, false alarms). The integration of clinical data is essential to prioritize suspect clusters for investigation, and for existing infections, a timely review of both the clinical and WGS results can hold promise to reduce HAIs. A richer understanding of cross-transmission events within healthcare settings will require the expansion of current surveillance approaches.