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.
In order to maximize the utility of future studies of trilobite ontogeny, we propose a set of standard practices that relate to the collection, nomenclature, description, depiction, and interpretation of ontogenetic series inferred from articulated specimens belonging to individual species. In some cases, these suggestions may also apply to ontogenetic studies of other fossilized taxa.
Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni, we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
The Clinical and Translational Science Awards (CTSA) Consortium, about 60 National Institutes of Health (NIH)-supported CTSA hubs at academic health care institutions nationwide, is charged with improving the clinical and translational research enterprise. Together with the NIH National Center for Advancing Translational Sciences (NCATS), the Consortium implemented Common Metrics and a shared performance improvement framework.
Initial implementation across hubs was assessed using quantitative and qualitative methods over a 19-month period. The primary outcome was implementation of three Common Metrics and the performance improvement framework. Challenges and facilitators were elicited.
Among 59 hubs with data, all began implementing Common Metrics, but about one-third had completed all activities for three metrics within the study period. The vast majority of hubs computed metric results and undertook activities to understand performance. Differences in completion appeared in developing and carrying out performance improvement plans. Seven key factors affected progress: hub size and resources, hub prior experience with performance management, alignment of local context with needs of the Common Metrics implementation, hub authority in the local institutional structure, hub engagement (including CTSA Principal Investigator involvement), stakeholder engagement, and attending training and coaching.
Implementing Common Metrics and performance improvement in a large network of research-focused organizations proved feasible but required substantial time and resources. Considerable heterogeneity across hubs in data systems, existing processes and personnel, organizational structures, and local priorities of home institutions created disparate experiences across hubs. Future metric-based performance management initiatives across heterogeneous local contexts should anticipate and account for these types of differences.
Heavy alcohol consumption is associated with poorer cognitive function in older adults. Although understudied in middle-aged adults, the relationship between alcohol and cognition may also be influenced by genetics such as the apolipoprotein (ApoE) ε4 allele, a risk factor for Alzheimer’s disease. We examined the relationship between alcohol consumption, ApoE genotype, and cognition in middle-aged adults and hypothesized that light and/or moderate drinkers (≤2 drinks per day) would show better cognitive performance than heavy drinkers or non-drinkers. Additionally, we hypothesized that the association between alcohol use and cognitive function would differ by ApoE genotype (ε4+ vs. ε4−).
Participants were 1266 men from the Vietnam Era Twin Study of Aging (VETSA; M age = 56; range 51–60) who completed a neuropsychological battery assessing seven cognitive abilities: general cognitive ability (GCA), episodic memory, processing speed, executive function, abstract reasoning, verbal fluency, and visuospatial ability. Alcohol consumption was categorized into five groups: never, former, light, moderate, and heavy.
In fully adjusted models, there was no significant main effect of alcohol consumption on cognitive functions. However, there was a significant interaction between alcohol consumption and ApoE ε4 status for GCA and episodic memory, such that the relationship of alcohol consumption and cognition was stronger in ε4 carriers. The ε4+ heavy drinking subgroup had the poorest GCA and episodic memory.
Presence of the ε4 allele may increase vulnerability to the deleterious effects of heavy alcohol consumption. Beneficial effects of light or moderate alcohol consumption were not observed.
To estimate costs associated with medication non-adherence over a 3-year follow-up period in the treatment of schizophrenia in routine clinical practice in Europe.
SOHO is a 3-year, prospective, observational study of 10972 outpatient participants across 10 European countries. Data were collected at baseline and at 6-month intervals up to 36 months. Medication adherence was assessed at each visit by participating psychiatrists during 4 weeks prior to the visit as: (1) not prescribed medication; (2) always adherent; (3) partially adherent; and (4) never adherent. In this post-hoc analysis, multivariate analyses were performed to compare the costs of resource use (inpatient stay, day care, psychiatrist visits and medication) in patients who were adherent, partially adherent, and non-adherent, using a log-link function. Adherence status was included as a time-varying variable, and other baseline patient characteristics were adjusted for. UK unit costs were applied to resource use.
Out of 5364 patients who were prescribed medication prior to baseline, 5.9% were non-adherent while 77.1% and 17.0% were adherent and partially adherent, respectively, at baseline. The average 6-month cost incurred by non-adherent patients was £2505 while that for adherent and partially adherent patients was £2029 and £2130 respectively. This difference was mainly due to inpatient costs. The inpatient costs incurred by non-adherent patients (£987) were almost double those for adherent patients (£475).
Non-adherence in schizophrenia was likely to incur more inpatient services, which may indicate poorer clinical prognosis. A study limitation is that adherence was assessed by investigators using a single-item measure.
Motor, perceptual, and cognitive functions affect driving competence. White matter hyperintensities (WMH) changes on brain MRI are associated structural brain changes along with cognitive and motor performance. The aim of this study was to investigate the association between WMH and driving ability in the elderly.
Participants (n = 540) were drawn from a nationwide, multicenter, hospital-based, longitudinal cohort study. Each participant underwent clinical evaluations, neuropsychological tests, and interview for caregiver including driving capacity, which was categorized as ‘now driving’, and ‘driving cessation (driving before, not now)’. A total 540 participants were divided into three groups (389 mild, 116 moderate, and 35 severe) depending on the degree of WMH. The same evaluations of them were followed after each year. The statistical analyses were performed using χ2 test, an analysis of variance (ANOVA), structured equation model (SEM), and generalized estimating equation (GEE).
In a SEM, greater baseline degree of WMH was directly associated with driving cessation regardless of cognitive and motor dysfunction (β = –0.110, P < 0.001). In GEE models controlling for age, sex, education, cognitive, and motor dysfunction, the more severe changes of the degree of WMH was associated with the faster change from ‘now driving’ state to ‘driving cessation’ state over time in the elderly (β = –0.508, P < 0.001).
In both cross-sectional and longitudinal aspects, the degree of WMH might be one of the predictive factors for driving cessation in the elderly, reflecting both motor and cognitive functions or independently.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Chlamydia trachomatis (CT) infection has been a major public health threat globally. Monitoring and prediction of CT epidemic status and trends are important for programme planning, allocating resources and assessing impact; however, such activities are limited in China. In this study, we aimed to apply a seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence of CT infection in Shenzhen city, China. The monthly incidence of CT between January 2008 and June 2019 in Shenzhen was used to fit and validate the SARIMA model. A seasonal fluctuation and a slightly increasing pattern of a long-term trend were revealed in the time series of CT incidence. The monthly CT incidence ranged from 4.80/100 000 to 21.56/100 000. The mean absolute percentage error value of the optimal model was 8.08%. The SARIMA model could be applied to effectively predict the short-term CT incidence in Shenzhen and provide support for the development of interventions for disease control and prevention.
Trimethoprim crystallizes in the triclinic space group P-1 (#2) with a = 10.5085(3), b = 10.5417(2), c = 8.05869(13) Å, α = 101.23371(21), β = 112.1787(3), γ = 112.6321(4)°, V = 743.729 Å3, and Z = 2. A reduced cell search in the Cambridge Structural Database yielded three previous structure determinations, using data collected at 100 K, 173 K, and room temperature. In this work, the sample was ordered from the United States Pharmacopeial Convention (USP) and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.412826 Å) powder diffraction data and optimized using density functional theory techniques. We found similar hydrogen bonding patterns with the previous determinations. In addition, we identified two C–H⋯O hydrogen bonds, which also contribute to the crystal energy. When comparing the previously reported trimethoprim structure determinations, the unit cell length lattice parameters were found to contract at lower temperatures, particularly 100 K. All structures show reasonable agreement, with unit cell length differences ranging between 0.05 and 0.15 Å. The diffraction data for this study were collected on beamline 11-BM at the Advanced Photon Source, and the powder X-ray diffraction pattern of the compound has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).
In this study, the thermal deformation of a machine tool structure due to the heat generated during operation was analyzed, and embedded cooling channels were applied to exchange the heat generated during the operation to achieve thermal error suppression. Then, the finite volume method was used to simulate the effect of cooling oil temperature on thermal deformation, and the effect of thermal suppression was experimentally studied using a feed system combined with a cooler to improve the positioning accuracy of the machine tool. In this study, the supply oil temperature in the structural cooling channels was found to significantly affect the position accuracy of the moving table and moving carrier. If the supply oil temperature in the cooling channels is consistent with the operational ambient temperature, the position accuracy of the moving table in the Y direction and the moving carrier in the X and Z directions has the best performance under different feed rates. From the thermal suppression experiments of the embedded cooling channels, the positioning accuracy of the feed system can be improved by approximately 25.5 % during the dynamic feeding process. Furthermore, when the hydrostatic guideway is cooled and dynamic feeding is conducted, positioning accuracy can be improved by up to 47.8 %. The machining accuracy can be improved by approximately 60 % on average by using the embedded cooling channels in this study. Therefore, thermal suppression by the cooling channels in this study can not only effectively improve the positioning accuracy but also enhance machining accuracy, proving that the method is effective for enhancing machine tool accuracy.
In the nearly a quarter of a century since the addition of the clinically significant distress/impairment criterion to the definition of PTSD in DSM-IV, little research has been done to examine the association of this criterion with symptom group criteria and with the numbing subgroup specifically. This study was conducted to examine these relationships in a large database of disaster survivors consistently studied across 12 different incidents of the full range of disaster typology.
Analysis was conducted on a merged database representing 1187 trauma-exposed survivors of 12 different disasters studied systematically. DSM-IV-TR criteria for disaster-related PTSD were assessed with the Diagnostic Interview Schedule.
PTSD Group C (avoidance/numbing) and numbing specifically were less common and more associated than other symptom groups with criterion F (distress/impairment). Consistently in multivariable models, group C and numbing were independently associated with criterion F. Group D (hyperarousal) was less strongly associated with criterion F. Neither group B (intrusion) nor avoidance were associated with criterion F.
In this and other studies, group C and numbing specifically have been shown to be associated with criterion F, which is consistent with the demonstration that group C and the numbing component specifically are central to the psychopathology of PTSD. The addition of the distress/impairment requirement broadly across the psychiatric diagnoses in DSM-IV added little value to PTSD symptom criteria. Future revisions of diagnostic criteria may benefit by carefully considering these findings to possibly re-include a prominent numbing symptom section.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
The authors demonstrate that gold-binding peptides displayed on the outer membrane of Escherichia coli enhance bioelectrochemical charge transfer by binding gold nanoparticles. Microbial fuel cells were run with different gold-binding peptides displayed and with different nanoparticle sizes, and the results were correlated with transmission electron microscopy (TEM) imaging of nanoparticle binding. When a gold-binding peptide is displayed and 5 nm gold nanoparticles are present, up to 4× power generation over E. coli not displaying a gold-binding peptide is observed. While an enhanced current is observed using the previously published M6G9, the largest enhancement is observed when a new longer peptide named M9G18 is used.
Habitat prioritization and corridor restoration are important steps for reconnecting fragmented habitats and species populations, and spatial modelling approaches are useful in identifying suitable habitat for elusive tropical rainforest mammals. The Endangered Bornean banteng Bos javanicus lowi, a wild bovid endemic to Borneo, occurs in habitat that is highly fragmented as a result of extensive agricultural expansion. Based on the species’ historical distribution in Sabah (Malaysia), we conducted camera-trap surveys in 14 forest reserves during 2011–2016. To assess suitable habitat for the banteng we used a presence-only maximum entropy (MaxEnt) approach with 11 spatial predictors, including climate, infrastructure, land cover and land use, and topography variables. We performed a least-cost path analysis using Linkage Mapper, to understand the resistance to movement through the landscape. The surveys comprised a total of 44,251 nights of camera trapping. We recorded banteng presence in 11 forest reserves. Key spatial predictors deemed to be important in predicting suitable habitat included soil associations (52.6%), distance to intact and logged forests (11.8%), precipitation in the driest quarter (10.8%), distance to agro-forest and regenerating forest (5.7%), and distance to oil palm plantations (5.1%). Circa 11% of Sabah had suitable habitat (7,719 km2), of which 12.2% was in protected forests, 60.4% was in production forests and 27.4% was in other areas. The least-cost path model predicted 21 linkages and a relatively high movement resistance between core habitats. Our models provide information about key habitat and movement resistance for bantengs through the landscape, which is crucial for constructive conservation strategies and land-use planning.
Ca and dairy product intakes may be inversely associated with all-cause and cause-specific mortality, and non-Ca components of dairy products, such as insulin-like growth factor-1, may be independently associated with mortality. We investigated associations of Ca and dairy product intakes with all-cause, all-cancer, colorectal cancer (CRC) and CHD mortality among 35 221 55- to 69-year-old women in the prospective Iowa Women’s Health Study, who were cancer-free in 1986. We assessed diet using a Willett FFQ, and associations using multivariable Cox proportional hazards regression. We estimated residuals from linear regression models of dairy products with dietary Ca to investigate total and specific dairy products independent of their Ca content. Through 2012, 18 687 participants died, including 4665 from cancer (including 574 from CRC) and 3603 from CHD. For those in the highest relative to the lowest quintiles of intake, the multivariable-adjusted hazard ratios (HR) and 95 % CI for total Ca (dietary plus supplemental) were 0·88 (0·83, 0·93; P trend=0·001) for all-cause mortality, 0·91 (0·81, 1·02; P trend=0·34) for all-cancer mortality, 0·60 (0·43, 0·83; P trend=0·002) for CRC mortality and 0·73 (0·64, 0·83; P trend <0·0001) for CHD mortality. The corresponding HR for associations of whole milk, whole milk residuals, and low-/non-fat milk residuals with all-cause mortality were 1·20 (95 % CI 1·13, 1·27), 1·20 (95 % CI 1·13, 1·28) and 0·91 (95 % CI 0·86, 0·96), respectively. These results suggest that Ca may be associated with lower risk of all-cause, CRC and CHD mortality, and that non-Ca components of milk may be independently associated with mortality.
OBJECTIVES/SPECIFIC AIMS: Intensive lifestyle change (e.g., the Diabetes Prevention Program) and metformin reduce type 2 diabetes risk among patients with prediabetes. However, real-world uptake remains low. Shared decision-making (SDM) may increase awareness and help patients select and follow through with informed options for diabetes prevention that are aligned with their preferences.The objective was to test the effectiveness of a prediabetes SDM intervention. METHODS/STUDY POPULATION: This was a cluster-randomized controlled trial in 20 primary care clinics within a large regional health system. Participants were overweight/obese adults with prediabetes (BMI>24 kg/m2 and HbA1c 5.7-6.4%) were enrolled from 10 SDM intervention clinics. Propensity score matching was used to identify control patients from 10 usual care clinics.Intervention clinic patients were invited to participate in a face-to-face SDM visit with a pharmacist who used a decision aid (DA) to describe prediabetes and four possible options for diabetes prevention; DPP, DPP +/− metformin, metformin only, or usual care. RESULTS/ANTICIPATED RESULTS: Uptake of DPP and/or metformin was higher among SDM participants (n=351) than controls receiving usual care (n = 1,028; 38% vs. 2%, p<.001). At 12-months follow-up, adjusted weight loss (lbs.) was greater among SDM participants than controls (−5.3 vs. −0.2, p < .001). DISCUSSION/SIGNIFICANCE OF IMPACT: A prediabetes SDM intervention led by pharmacists increased patient engagement in evidence-based options for diabetes prevention and was associated with significantly greater uptake of DPP and/or metformin at 4-months and weight loss at 12-months. Prediabetes SDM may be a promising approach to enhance prevention efforts among patients at increased risk.
Many seed quality tests are conducted by first randomly assigning seeds into replicates of a given size. The replicate results are then used to check whether or not any problems occur in the realization of the test. The two main tools developed for this verification are the ratio of the observed variance of the replicate results to a theoretical variance and the tolerance for the range of the results. In this paper, we derive the theoretical distribution and its related properties of the sequence of numbers of seeds with a given quality attribute present in the replicates. From these theoretical results, we revisit the two quality checking tools widely used for the germination test. We show a precaution to be taken when relying on the variance ratio to check for under- or over-dispersion of the replicate results. This has led to the development of tables providing credible intervals of the variance ratio. The International Seed Testing Association tolerance tables for the range of the results are also compared with tolerances computed from the exact theoretical distribution of the range, leading us to recommend a revision of these tables.
Childhood maltreatment is one of the strongest predictors of adulthood depression and alterations to circulating levels of inflammatory markers is one putative mechanism mediating risk or resilience.
To determine the effects of childhood maltreatment on circulating levels of 41 inflammatory markers in healthy individuals and those with a major depressive disorder (MDD) diagnosis.
We investigated the association of childhood maltreatment with levels of 41 inflammatory markers in two groups, 164 patients with MDD and 301 controls, using multiplex electrochemiluminescence methods applied to blood serum.
Childhood maltreatment was not associated with altered inflammatory markers in either group after multiple testing correction. Body mass index (BMI) exerted strong effects on interleukin-6 and C-reactive protein levels in those with MDD.
Childhood maltreatment did not exert effects on inflammatory marker levels in either the participants with MDD or the control group in our study. Our results instead highlight the more pertinent influence of BMI.
Declaration of interest
D.A.C. and H.W. work for Eli Lilly Inc. R.N. has received speaker fees from Sunovion, Jansen and Lundbeck. G.B. has received consultancy fees and funding from Eli Lilly. R.H.M.-W. has received consultancy fees or has a financial relationship with AstraZeneca, Bristol-Myers Squibb, Cyberonics, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, MyTomorrows, Otsuka, Pfizer, Pulse, Roche, Servier, SPIMACO and Sunovian. I.M.A. has received consultancy fees or has a financial relationship with Alkermes, Lundbeck, Lundbeck/Otsuka, and Servier. S.W. has sat on an advisory board for Sunovion, Allergan and has received speaker fees from Astra Zeneca. A.H.Y. has received honoraria for speaking from Astra Zeneca, Lundbeck, Eli Lilly, Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion, Janssen; and research grant support from Janssen. A.J.C. has received honoraria for speaking from Astra Zeneca, honoraria for consulting with Allergan, Livanova and Lundbeck and research grant support from Lundbeck.