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Existing modelling tools, developed to aid the design of efficient molecular wires and to better understand their charge‐transport behaviour and mechanism, have limitations in accuracy and computational cost. Further research is required to develop faster and more precise methods that can yield information on how charge transport properties are impacted by changes in the chemical structure of a molecular wire. In this study, we report a clear semilogarithmic correlation between charge transport efficiency and nuclear magnetic resonance chemical shifts in multiple series of molecular wires, also accounting for the presence of chemical substituents. The NMR data was used to inform a simple tight‐binding model that accurately captures the experimental single‐molecule conductance values, especially useful in this case as more sophisticated density functional theory calculations fail due to inherent limitations. Our study demonstrates the potential of NMR spectroscopy as a valuable tool for characterising, rationalising, and gaining additional insights on the charge transport properties of single‐molecule junctions. [ABSTRACT FROM AUTHOR]

Existing modelling tools, developed to aid the design of efficient molecular wires and to better understand their charge‐transport behaviour and mechanism, have limitations in accuracy and computational cost. Further research is required to develop faster and more precise methods that can yield information on how charge transport properties are impacted by changes in the chemical structure of a molecular wire. In this study, we report a clear semilogarithmic correlation between charge transport efficiency and nuclear magnetic resonance chemical shifts in multiple series of molecular wires, also accounting for the presence of chemical substituents. The NMR data was used to inform a simple tight‐binding model that accurately captures the experimental single‐molecule conductance values, especially useful in this case as more sophisticated density functional theory calculations fail due to inherent limitations. Our study demonstrates the potential of NMR spectroscopy as a valuable tool for characterising, rationalising, and gaining additional insights on the charge transport properties of single‐molecule junctions. [ABSTRACT FROM AUTHOR]

Studies of vertebrate bone biomechanics often focus on skeletal adaptations at upper extremes of body mass, disregarding the importance of skeletal adaptations at lower extremes. Yet mammals are ancestrally small and most modern species have masses under 5 kg, so the evolution of morphology and function at small size should be prioritized for understanding how mammals subsist. We examined allometric scaling of lumbar vertebrae in the small-bodied Philippine endemic rodents known as cloud rats, which vary in mass across two orders of magnitude (15.5 g–2700 g). External vertebral dimensions scale with isometry or positive allometry, likely relating to body size and nuances in quadrupedal posture. In contrast to most mammalian trabecular bone studies, bone volume fraction and trabecular thickness scale with positive allometry and isometry, respectively. It is physiologically impossible for these trends to continue to the upper extremes of mammalian body size, and we demonstrate a fundamental difference in trabecular bone allometry between large- and small-bodied mammals. These findings have important implications for the biomechanical capabilities of mammalian bone at small body size; for the selective pressures that govern skeletal evolution in small mammals; and for the way we define 'small' and 'large' in the context of vertebrate skeletons. [ABSTRACT FROM AUTHOR]

Sleep quality and sleep duration are important for children's physical and mental health. Mental health diagnoses and sleep disturbances may be interlinked. We sought to identify the methods used to assess sleep in paediatric community‐based mental health programmes. A systematic review was conducted using an a priori protocol to ascertain the sleep assessment methods used in paediatric community‐based mental health programmes. Children for this review were defined as any person under the age of 19. Cochrane Library, CINAHL, Web of Science, ProQuest, APA PsycInfo, and PubMed databases were searched from January 2021 to March 2022. Of the 320 records screened, 314 records were excluded. Six studies were included for analysis. A variety of validated and non‐validated sleep instruments were used to measure sleep quality and a range of sleep disturbances in community health programmes for children. There were a limited number of studies associated with sleep assessment in paediatric community‐based settings suggesting this is an area of research that may be understudied. Sleep questionnaires were predominately completed by parents or guardians. Further research is required to establish the most effective method for screening sleep behaviour in paediatric community mental health programmes to understand the impact of sleep in the recovery of children and adolescents with mental health disorders. [ABSTRACT FROM AUTHOR]

Introduced Phragmites (Phragmites australis ssp. australis) forms part of an invasion assemblage in North America that includes non-native insect herbivores and parasitoids, some of which are now found on both the introduced and native subspecies of Phragmites (P. australis ssp. americanus). This insect assemblage is key to understanding the impact of P. australis invasion and interpreting the efficacy of biological control used against introduced P. australis. Our study provides the first dedicated comparison of insect assemblages associated with native and introduced P. australis in Canada. From a 2016 to 2017 survey of 28 geographically paired sites across Ontario, Canada, fourteen insect taxa were recorded from both subspecies. Genotype had no effect on α-diversity but stem attack rates from at least one herbivore were higher on native populations than on paired introduced populations (+ 18.6%). We report the first record of Chaetococcus phragmitis (Homoptera: Pseudococcidae) and Rhizedra lutosa (Lepidoptera: Noctuidae) in Canada and of R. lutosa and Lasioptera hungarica (Diptera: Cecidomyiidae) on native P. australis in North America. [ABSTRACT FROM AUTHOR]

Young adult (YA) cancer survivors often experience social isolation. Mobile apps facilitate peer-to-peer connections, yet little is known about their use. YA survivors (N = 181) were surveyed about a peer-to-peer cancer support app. Among those with it downloaded, 36% reported daily/weekly use. One-to-one messaging and group chat features were easy-to-use and useful, but facilitation of social presence was variable. Within group chats, 55% participated in discussions; 45% observed conversations without contributing. The app was helpful for convenient access to peer support (84%), particularly when offline social networks were inadequate (83%); some (16–25%) reported nervousness initiating connections. Qualitative feedback identified facilitators and barriers to adoption and sustained engagement. Recommendations centered on improving design and logistical factors and facilitating in-app connections. App-based peer support is promising for addressing social isolation among YA survivors. Future research should examine theory-based communication and design features to encourage meaningful engagement and longitudinal effects on psychosocial outcomes. [ABSTRACT FROM AUTHOR]

The presented six component force balance is a novel design used for many of the force measurements on hydrofoils and other bodies in the University of Tasmania's cavitation tunnel. This balance is a versatile piece of equipment, the distribution of its six load cells gives it a high degree of sensitivity and stiffness in all directions. The accuracy of the balance in operating conditions has yet to be defined and its use for investigations of low frequency fluid-structure interactions warrants an analysis of its dynamic properties. This paper outlines a critical analysis of the balances calibration methodologies and its measurement uncertainties. A dynamic vibration model was built and validated with finite element modelling and experiment to give a prediction of the force balances natural frequencies and how they change with different test article mass and added masses. These results provide confidence in the data produced by this device and guide future experimental investigations into fluid structure interactions. [ABSTRACT FROM AUTHOR]

Background: Early warning systems (EWSs) are used to assist clinical judgment in the detection of acute deterioration to avoid or reduce adverse events including unanticipated cardiopulmonary arrest, admission to the intensive care unit and death. Sometimes healthcare professionals (HCPs) do not trigger the alarm and escalate for help according to the EWS protocol and it is unclear why this is the case. The aim of this qualitative evidence synthesis was to answer the question 'why do HCPs fail to escalate care according to EWS protocols?' The findings will inform the update of the National Clinical Effectiveness Committee (NCEC) National Clinical Guideline No. 1 Irish National Early Warning System (INEWS).Methods: A systematic search of the published and grey literature was conducted (until February 2018). Data extraction and quality appraisal were conducted by two reviewers independently using standardised data extraction forms and quality appraisal tools. A thematic synthesis was conducted by two reviewers of the qualitative studies included and categorised into the barriers and facilitators of escalation. GRADE CERQual was used to assess the certainty of the evidence.Results: Eighteen studies incorporating a variety of HCPs across seven countries were included. The barriers and facilitators to the escalation of care according to EWS protocols were developed into five overarching themes: Governance, Rapid Response Team (RRT) Response, Professional Boundaries, Clinical Experience, and EWS parameters. Barriers to escalation included: Lack of Standardisation, Resources, Lack of accountability, RRT behaviours, Fear, Hierarchy, Increased Conflict, Over confidence, Lack of confidence, and Patient variability. Facilitators included: Accountability, Standardisation, Resources, RRT behaviours, Expertise, Additional support, License to escalate, Bridge across boundaries, Clinical confidence, empowerment, Clinical judgment, and a tool for detecting deterioration. These are all individual yet inter-related barriers and facilitators to escalation.Conclusions: The findings of this qualitative evidence synthesis provide insight into the real world experience of HCPs when using EWSs. This in turn has the potential to inform policy-makers and HCPs as well as hospital management about emergency response system-related issues in practice and the changes needed to address barriers and facilitators and improve patient safety and quality of care. [ABSTRACT FROM AUTHOR]

Teeth lie at the interface between an animal and its environment and, with some exceptions, act as a major component of resource procurement through food acquisition and processing. Therefore, the shape of a tooth is closely tied to the type of food being eaten. This tight relationship is of use to biologists describing the natural history of species and given the high instance of tooth preservation in the fossil record, is especially useful for paleontologists. However, correlating gross tooth morphology to diet is only part of the story, and much more can be learned through the study of dental biomechanics. We can explore the mechanics of how teeth work, how different shapes evolved, and the underlying forces that constrain tooth shape. This review aims to provide an overview of the research on dental biomechanics, in both mammalian and non-mammalian teeth, and to synthesize two main approaches to dental biomechanics to develop an integrative framework for classifying and evaluating dental functional morphology. This framework relates food material properties to the dynamics of food processing, in particular how teeth transfer energy to food items, and how these mechanical considerations may have shaped the evolution of tooth morphology. We also review advances in technology and new techniques that have allowed more in-depth studies of tooth form and function. [ABSTRACT FROM AUTHOR]

The phase II objective is to determine if oral azacitidine + R-miniCHOP should be tested further against R-miniCHOP based on estimates of 1-year PFS. S1918 incorporates the FIL Tool for baseline frailty assessment and a serial comprehensive geriatric assessment to evaluate effects of therapy on quality of life and functional status. Patients receive prephase therapy with prednisone 60-100 mg × 4-7 days to improve performance status and decrease early treatment-related mortality (Owens CN et al., 2015; Pfreundschuh M et al., 2008). [Extracted from the article]

Funding: NIH/NCI/NCTN grants U10CA180888/U10CA180819. Following a safety run-in of 12 patients per each experimental arm, the randomized Phase II study will enroll 180 patients to Arm 1: tafa-len + tazemetostat; Arm 2: tafa-len (control); or Arm 3: tafa-len + zanubrutinib (Figure 1). S2207: RANDOMIZED PHASE II STUDY OF THE ADDITION OF TARGETED AGENTS TO TAFASITAMAB-LENALIDOMIDE IN TRANSPLANT INELIGIBLE PATIENTS WITH RELAPSED/REFRACTORY LBCL. [Extracted from the article]

A "FUNCTIONAL CURE" MAY BE ACHIEVABLE IN A SUBSET OF PATIENTS WITH FOLLICULAR LYMPHOMA TREATED WITH CHEMOIMMUNOTHERAPY: 15-YEAR FOLLOW-UP OF PHASE III SWOG-S0016 S0016 enrolled patients with untreated advanced FL (bulky stage II or III-IV) between 2001 and 2008 and randomized them to CHOP × 6 followed by (131) I-tositumomab radioimmunotherapy (CHOP-RIT) or CHOP-R × 6; no maintenance was included. B Background: b Follicular lymphoma (FL) is considered incurable with current therapies which include chemoimmunotherapy as the standard of care for first line. [Extracted from the article]

B Conclusions: b Immuno-architectural patterns of higher focal Ki-67 staining in grade 1-2 FL are significantly associated with POD24, and high Ki-67 staining in peripheral patterns is associated with inferior 5-yr OS. B Background: b Follicular lymphoma (FL) is the most prevalent indolent B-cell non-Hodgkin lymphoma (B-NHL). Ki-67 staining is a widely available biomarker without a defined role in FL, however has potential to better highlight the tumor microenvironment (TME) based on its known colocalization with subsets of T-cells. [Extracted from the article]

Understanding the potential outcomes of interactions between native insects and invasive plants is important for predicting the magnitude of effects caused by an invader in its new environment. Here, we investigate the ability of the native western leaf beetle, Chrysochus cobaltinus, and a hybrid of North American Chrysochus species, (hybrid of eastern C. auratus and western C. cobaltinus) to initiate a novel association with introduced pale swallow-wort (Vincetoxicum rossicum) (Apocynaceae). This European vine is invasive in eastern North America but has not yet been encountered by C. cobaltinus in the field. Lab tests demonstrate that C. cobaltinus can feed on introduced V. rossicum foliage, and that they are not locally-specialized to hosts from which they were collected. Thus, adult C. cobaltinus may use V. rossicum as a transient host when encountered in the field. Chrysochus hybrids were unable to feed on introduced V. rossicum (similar to their C. auratus parents) but did feed on native North American Asclepias spp. (similar to their C. cobaltinus parents). Hybridization and subsequent gene introgression may explain both decreased feeding by western C. cobaltinus and increased feeding by eastern C. auratus on native Asclepias spp. in this region, but does not appear to affect feeding on V. rossicum. We predict the potential novel association between native C. cobaltinus and invasive V. rossicum will have a positive or neutral outcome for the beetles, but is unlikely to slow the spread of the vine in North America unless further adaptation occurs. [ABSTRACT FROM AUTHOR]

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines. [ABSTRACT FROM AUTHOR]

Aims: Attendance at structured diabetes education has been recommended internationally for all people with Type 2 diabetes. However, attendance rates are consistently low. This qualitative study aimed to explore experiences of attending and delivering Type 2 diabetes structured education programmes in Ireland and barriers and facilitators to attendance. Methods: People with Type 2 diabetes who had attended one of the three programmes delivered in Ireland and educators from the three programmes took part in semi‐structured telephone interviews. Interviews were audio‐taped, transcribed and analysed using inductive thematic analysis. Results: Twelve attendees and 14 educators were interviewed. Two themes were identified in relation to experiences of programme attendance and delivery: 'Structured education: addressing an unmet need' and 'The problem of non‐attendance'. The third theme 'Barriers to attendance: can't go, won't go, don't know and poor system flow' outlined how practicalities of attending, lack of knowledge of the existence and benefits, and limited resources and support for education within the diabetes care pathway impacts on attendance. The final theme 'Supporting attendance: healthcare professionals and the diabetes care pathway' describes facilitators to participants' attendance and the strategies educators perceived to be important in increasing attendance. Conclusions: Healthcare professionals have an important role in improving attendance at structured diabetes education programmes. Improving attendance may require promotion by healthcare professionals and for education to be better embedded and supported within the diabetes care pathway. What's new?: This is the first time that experiences, and barriers and facilitators to attendance at Type 2 diabetes structured education programmes have been explored among educators and attendees.Similar to a previous review, we identified 'Can't go' and 'Won't go' reasons for non‐attendance.We also identified two new categories: 'Don't know' – lack of knowledge of the existence and benefits of programmes and 'Poor system flow' – issues with healthcare system resources and lack of importance placed on education.Healthcare professionals have an important role in promoting attendance.Improving attendance may require education to be better embedded and supported within the diabetes care pathway. [ABSTRACT FROM AUTHOR]

The author focuses on prospective clinical trial registration, a process in which clinical researchers publicize trial methodology details and conduct before participants are enrolled. Topics discussed include the purpose of prospectively registering a trial, such as increased transparency and decreased selective reporting about results; the role of journals in publication of clinical trial data; and the need for improving the consistency between trial registration and resulting articles.

Aims To systematically review the evidence on the costs and cost-effectiveness of self-management support interventions for people with diabetes. Background Self-management support is the provision of education and supportive interventions to increase patients' skills and confidence in managing their health problems, potentially leading to improvements in HbA1c levels in people with diabetes. Methods Randomized controlled trials, observational studies or economic modelling studies were eligible for inclusion in the review. The target population was adults with diabetes. Interventions had to have a substantial component of self-management support and be compared with routine care. Study quality was evaluated using the Consensus on Health Economic Criteria and International Society of Pharmacoeconomic Outcomes Research questionnaires. A narrative review approach was used. Results A total of 16 costing and 21 cost-effectiveness studies of a range of self-management support interventions were identified. There was reasonably consistent evidence across 22 studies evaluating education self-management support programmes suggesting these interventions are cost-effective or superior to usual care. Telemedicine-type interventions were more expensive than usual care and potentially not cost-effective. There was insufficient evidence regarding the other types of self-management interventions, including pharmacist-led and behavioural interventions. The identified studies were predominantly of poor quality, with outcomes based on short-term follow-up data and study designs at high risk of bias. Conclusions Self-management support education programmes may be cost-effective. There was limited evidence regarding other formats of self-management support interventions. The poor quality of many of the studies undermines the evidence base regarding the economic efficiency of self-management support interventions for people with diabetes. [ABSTRACT FROM AUTHOR]

Native insects can form novel associations with introduced invasive plants and use them as a food source. The recent introduction into eastern North America of a nonnative European vine, Vincetoxicum rossicum (Kleopow) Barbar., allows us to examine the initial response of a native chrysomelid beetle, Chrysochus auratus F., that feeds on native plants in the same family as V. rossicum (Apocynaceae). We tested C. auratus on V. rossicum and closely related or co-occurring native plants (Apocynum spp., Asclepias spp., and Solidago canadensis L.) using all life stages of the beetle in lab, garden, and field experiments. Experiments measured feeding (presence or absence and amount), survival, oviposition, and whether previous exposure to V. rossicum in the lab or field affected adult beetle feeding. Beetles fed significantly less on V. rossicum than on native Apocynum hosts. Adult beetles engaged in exploratory feeding on leaves of V. rossicum and survived up to 10 d. Females oviposited on V. rossicum, eggs hatched, and larvae fed initially on the roots; however, no larvae survived beyond second instar. Beetles collected from Apocynum cannabinum L. field sites intermixed with V. rossicum were less likely to feed on this novel nonnative host than those collected from colonies further from and less likely to be exposed to V. rossicum (>5km). Our experimental work indicates that V. rossicum may act as an oviposition sink for C. auratus and that this native beetle has not adapted to survive on this recently introduced novel host plant. [ABSTRACT FROM AUTHOR]

What is known and objective Paritaprevir/ritonavir/ombitasvir+dasabuvir (Pr OD) is a direct-acting antiviral ( DAA) approved for the treatment of chronic hepatitis C virus. We report on a probable interaction between Pr OD with ribavirin and warfarin. Case description Two weeks after the start of Pr OD with ribavirin, the patient's international normalized ratio ( INR) became subtherapeutic. Eleven weeks into therapy and following a 125% total increase in the weekly warfarin dose, therapeutic INR was achieved. Thirteen days after DAA therapy was completed and discontinued, the patient's INR became critically supratherapeutic. What is new and conclusion Patients on Pr OD plus ribavirin with warfarin should have INR followed closely upon initiation and discontinuation of therapy due to a probable drug interaction. [ABSTRACT FROM AUTHOR]

What is known and objective Although non-steroidal anti-inflammatory drugs ( NSAIDs) have been studied in randomized, controlled trials and meta-analyses in an effort to determine their cardiovascular ( CV) risks, no consensus has been reached. These studies continue to raise questions, including whether cyclooxygenase-2 ( COX-2) selectivity plays a role in conferring CV risk. We performed a meta-analysis of current literature to determine whether COX-2 selectivity leads to an increased CV risk. Methods We utilized randomized, controlled trials and prospective cohort studies. We selected eight NSAIDs based on popularity and COX selectivity and conducted a search of the MEDLINE, EMBASE, and Cochrane databases. Primary endpoints included any myocardial infarction (MI), any stroke, CV death, and a combination of all three (composite CV outcomes). Twenty-six studies were found that met inclusion and exclusion criteria. Comparisons were made between all included drugs, against placebo, and against non-selective NSAIDs (nsNSAIDs). Drugs were also compared against COX-2 selective inhibitors (COXIBs) with and without inclusion of rofecoxib. Results and discussion Incidence of MI was increased by rofecoxib in all comparison categories [all NSAIDs ( OR: 1·811, 95% CI: 1·379-2·378), placebo ( OR: 1·655: 95% CI: 1·029-2·661), ns NSAIDs ( OR: 2·155, 95% CI: 1·146-4·053), and COXIBs ( OR: 1·800, 95% CI: 1·217-2·662)], but was decreased by celecoxib and naproxen in the COXIB comparison [(OR: 0·583, 95% CI: 0·396-0·857) and (OR: 0·609, 95% CI: 0·375-0·989, respectively]. Incidence of stroke was increased by rofecoxib in comparisons with all NSAIDs and other COXIBs [( OR: 1·488, 95% CI: 1·027-2·155) and ( OR: 1·933, 95% CI: 1·052-3·549), respectively]. Incidence of stroke was decreased by celecoxib when compared with all NSAIDs, nsNSAIDs, and COXIBs [( OR: 0·603, 95% CI: 0·410-0·887), ( OR: 0·517, 95% CI: 0·287-0·929), and ( OR: 0·509, 95% CI: 0·280-0·925), respectively]. No NSAID reached statistical significance in regard to CV death. Incidence of the composite endpoint was increased by rofecoxib when compared against all NSAIDs, placebo, and other COXIBs [( OR: 1·612, 95% CI: 1·313-1·981), ( OR: 1·572, 95% CI: 1·123-2·201) and ( OR: 1·838, 95% CI: 1·323-2·554), respectively]. Incidence of composite endpoint was decreased by celecoxib in the all NSAIDs and COXIBs comparisons [( OR: 0·805, 95% CI: 0·658-0·986) and ( OR: 0·557, 95% CI: 0.404-0.767), respectively]. When rofecoxib was removed from the COXIBs group, no difference was found with any comparison, suggesting rofecoxib skewed the data. What is new and conclusion This instead of the meta-analysis suggests that COX-2 selectivity may not play a role in the CV risk of NSAIDs. Rofecoxib was the only drug to demonstrate harm and skewed the data of the COX-2 selective group. [ABSTRACT FROM AUTHOR]

Background: Assessment and reporting of adverse events (AEs) in studies of perioperative interventions is critical given the potential for unintended and preventable iatrogenic morbidity and mortality. This focused review evaluated the quality of AE assessment and reporting in acute post-operative pain treatment trials. Since older analgesics (e.g., opioids, NSAIDs) already have a well-characterized safety profile, we concentrated on trials of pregabalin and gabapentin as a representative sample of studies where the perioperative safety profile was relatively unknown.Methods: We reviewed primary reports of trials of pregabalin and gabapentin for treatment of acute post-operative pain for: (1) adherence to the 10 recommendations from the 'CONSORT Extension for Harms,' (2) AE assessment method, (3) timing of AE assessment and reporting, and (4) assessment and reporting of AE severity.Results: We identified 31 trials of pregabalin and 59 of gabapentin. The median number of CONSORT harms recommendations that were satisfied was 7 of 10. The most common (41%) method of AE assessment was direct questioning about specific AEs by investigators. However, AE assessment method was not described in 18% of trials. AE assessments were reported for specified perioperative time points in only 24% of trials. Of greatest concern, no AE data were reported whatsoever in 8 of the included publications.Conclusions: Considerable widespread improvements are needed in AE reporting for post-operative pain treatment trials. In addition to heightened awareness among clinical investigators, mandatory journal editorial policies may further facilitate improvements in safety assessment and reporting. [ABSTRACT FROM AUTHOR]

Objective: To determine the long-term effectiveness of a complex intervention in primary care aimed at improving outcomes for patients with coronary heart disease. Design: A 6-year follow-up of a cluster randomised controlled trial, which found after 18 months that both total and cardiovascular hospital admissions were significantly reduced in intervention practices (8% absolute reduction). Setting: 48 general practices in the Republic of Ireland and Northern Ireland. Participants: 903 patients with established coronary heart disease at baseline in the original trial. Intervention: The original intervention consisted of tailored practice and patient plans; training sessions for practitioners in medication prescribing and behavioural change; and regular patient recall system. Control practices provided usual care. Following the intervention period, all supports from the research team to intervention practices ceased. Outcome measures: Primary outcome: hospital admissions, all cause and cardiovascular; secondary outcomes: mortality; blood pressure and cholesterol control. Results: At 6-year follow-up, data were collected from practice records of 696 patients (77%). For those who had died, we censored their data at the point of death and cause of death was established. There were no significant differences between the intervention and control practices in either total (OR 0.83 (95% CI 0.54 to 1.28)) or cardiovascular hospital admissions (OR 0.91 (95% CI 0.49 to 1.65)). We confirmed mortality status of 886 of the original 903 patients (98%). There were no significant differences in mortality (15% in intervention and 16% in control) or in the proportions of patients above target control for systolic blood pressure or total cholesterol. Conclusions: Initial significant differences in the numbers of total and cardiovascular hospital admissions were not maintained at 6 years and no differences were found in mortality or blood pressure and cholesterol control. Policymakers need to continue to assess the effectiveness of previously efficacious programmes. [ABSTRACT FROM AUTHOR]

Structured Abstract Objectives To determine minimal dose levels required for local inhibition of orthodontic relapse by recombinant OPG protein ( OPG-Fc), while also determining effects of injected OPG-Fc on alveolar bone and long bone. Setting and Sample Population The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Eighteen male Sprague Dawley rats. Materials & Methods Maxillary molars were moved with nickel-titanium springs and then allowed to relapse in Sprague Dawley rats. Upon appliance removal, animals were injected with a single dose of 1.0 mg/kg OPG-Fc, 0.1 mg/kg OPG-Fc, or phosphate-buffered saline (vehicle) just distal to the molar teeth. Tooth movement measurements were made from stone casts, which were scanned and digitally measured. Alveolar tissues were examined by histology. Micro-computed tomography was used to quantify changes in alveolar and femur bone. Results Local injection of OPG-Fc inhibited molar but not incisor relapse, when compared to vehicle-injected animals. No significant differences in alveolar or femur bone were seen between the three treatment groups after 24 days of relapse. Conclusions Our results demonstrate that a single local injection of OPG-Fc effectively inhibits orthodontic relapse, with minimal systemic bone metabolic effects. Our results also show that a single injection of OPG-Fc will influence tooth movement only in teeth close to the injection site. These findings indicate that OPG-Fc has potential as a safe and effective pharmacological means to locally control osteoclasts, for uses such as maintaining anchorage during orthodontic tooth movement and preventing orthodontic relapse in humans. [ABSTRACT FROM AUTHOR]

What is known and objective Fibromyalgia is a painful disease affecting 1-2% of the United States population. Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and milnacipran, are well studied and frequently used for treating this disorder. However, efficacy data are limited for the SNRI venlafaxine despite its use in nearly a quarter of patients with fibromyalgia. Accordingly, we systematically reviewed the efficacy of venlafaxine for treatment of fibromyalgia. Methods PubMed, Web of Science and the Cochrane Database were searched using the terms 'venlafaxine' and 'fibromyalgia'. Results were classified as primary studies or review articles based on abstract review. References of review articles were evaluated to ensure no primary studies evaluating venlafaxine were overlooked. All clinical studies that investigated venlafaxine for the treatment of fibromyalgia were included and graded on strength of evidence. Results and discussion Five studies met the inclusion criteria, including 4 open-label cohort studies and 1 randomized, controlled trial. Study durations ranged from 6 weeks to 6 months, and study sizes ranged from 11 to 102 participants. Four of the five published studies reported improvement in at least one outcome. Generally consistent improvements were observed in pain-related outcome measures, including the Fibromyalgia Impact Questionnaire (range, 26-29% reduction; n = 2 studies), Visual Analog Scale (range, 36-45% reduction; n = 2 studies), McGill Pain Questionnaire (48% reduction; n = 1 study) and Clinical Global Impression scale (51% had significant score change; n = 1 study). However, the few studies identified were limited by small sample size, inconsistent use of outcomes and methodological concerns. What is new and conclusion Studies assessing the efficacy of venlafaxine in the treatment of fibromyalgia to date have been limited by small sample size, inconsistent venlafaxine dosing, lack of placebo control and lack of blinding. In the context of these limitations, venlafaxine appears to be at least modestly effective in treating fibromyalgia. Larger randomized controlled trials are needed to further elucidate the full benefit of venlafaxine. [ABSTRACT FROM AUTHOR]

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and bone mineral during space flight, which alters the endocrine regulation of calcium metabolism. Physical, pharmacologic, and nutritional means have been used to counteract these changes. In 2012, heavy resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce loss of bone mineral density on long-duration International Space Station missions. Uncertainty continues to exist, however, as to whether the bone is as strong after flight as it was before flight and whether nutritional and exercise prescriptions can be optimized during space flight. Findings from these studies not only will help future space explorers but also will broaden our understanding of the regulation of bone and calcium homeostasis on Earth. [ABSTRACT FROM AUTHOR]

The p66Shc adapter protein regulates the morphogenesis and epithelial maturation of fetal mouse lungs. Am J Physiol Lung Cell Mol Physiol 306: L316-L325, 2014. First published December 27, 2013; doi:10.1152/ajplung.00062.2013.--Many signaling pathways are mediated by Shc adapter proteins that, in turn, are expressed as three isoforms with distinct functions. The p66Shc isoform antagonizes proliferation, regulates oxidative stress, and mediates apoptosis. It is highly expressed in the canalicular but not the later stages of mouse lung development, and its expression persists in bronchopulmonary dysplasia, a chronic disease associated with premature birth. These observations suggest that p66Shc has a developmental function. However, constitutive p66Shc deletion yields no morphological phenotype, and the structure of the Shc gene precludes its inducible deletion. To elucidate its function in lung development, we transfected p66Shc or nonsilencing small-interfering RNA (siRNA) into the epithelia of embryonic day 11 mouse lungs that were then cultured for 3 days and analyzed morphometrically. To assess cellular proliferation and epithelial differentiation, lung explants were immunostained and immunoblotted for p66Shc, proliferating cell nuclear antigen (PCNA), the proximal airway differentiation antigens Clara cell 10-kDa protein (CC10) and thyroid transcription factor (TTF)-1, and the alveolar surfactant proteins (SP)-A, -B, and -C. Explants transfected with nonsilencing siRNA demonstrated specific epithelial uptake and normal morphological development relative to uninjected controls. In contrast, transfection with p66Shc siRNA significantly increased lumenal cross-sectional areas, decreased branching, and increased epithelial proliferation (P < 0.05 for all). Relative to controls, the expression of SP-B, SP-C, CC10, and TTF-1 was decreased by p66Shc knockdown. SP-A was not expressed in either control or treated lungs. These data suggest that p66Shc attenuates epithelial proliferation while promoting both distal and proximal epithelial maturation. [ABSTRACT FROM AUTHOR]

This review seeks to provide a current overview of musculoskeletal pain in overweight and obese children. Databases searched were Academic Search Complete, CINAHL, Medline, Proquest Health and Medical Complete, Scopus, Google Scholar, SPORTDiscuss and Trove for studies published between 1 January 2000 and 30 December 2012. We used a broad definition of children within a 3- to 18-year age range. The search strategy included the following terms: obesity, morbid obesity, overweight, pain, musculoskeletal pain, child, adolescent, chronic pain, back pain, lower back pain, knee pain, hip pain, foot pain and pelvic pain. Two authors independently assessed each record, and any disagreement was resolved by the third author. Data were analysed using a narrative thematic approach owing to the heterogeneity of reported outcome measures. Ninety-seven records were initially identified using a variety of terms associated with children, obesity and musculoskeletal pain. Ten studies were included for thematic analysis when predetermined inclusion criteria were applied. Bone deformity and dysfunction, pain reporting and the impact of children being overweight or obese on physical activity, exercise and quality of life were the three themes identified from the literature. Chronic pain, obesity and a reduction in physical functioning and activity may contribute to a cycle of weight gain that affects a child's quality of life. Future studies are required to examine the sequela of overweight and obese children experiencing chronic musculoskeletal pain. [ABSTRACT FROM AUTHOR]

This review seeks to provide a current overview of musculoskeletal pain in overweight and obese children. Databases searched were Academic Search Complete, CINAHL, Medline, Proquest Health and Medical Complete, Scopus, Google Scholar, SPORTDiscuss and Trove for studies published between 1 January 2000 and 30 December 2012. We used a broad definition of children within a 3- to 18-year age range. The search strategy included the following terms: obesity, morbid obesity, overweight, pain, musculoskeletal pain, child, adolescent, chronic pain, back pain, lower back pain, knee pain, hip pain, foot pain and pelvic pain. Two authors independently assessed each record, and any disagreement was resolved by the third author. Data were analysed using a narrative thematic approach owing to the heterogeneity of reported outcome measures. Ninety-seven records were initially identified using a variety of terms associated with children, obesity and musculoskeletal pain. Ten studies were included for thematic analysis when predetermined inclusion criteria were applied. Bone deformity and dysfunction, pain reporting and the impact of children being overweight or obese on physical activity, exercise and quality of life were the three themes identified from the literature. Chronic pain, obesity and a reduction in physical functioning and activity may contribute to a cycle of weight gain that affects a child's quality of life. Future studies are required to examine the sequela of overweight and obese children experiencing chronic musculoskeletal pain. [ABSTRACT FROM AUTHOR]

INFORMAS (International Network for Food and Obesity/non-communicable diseases Research, Monitoring and Action Support) aims to monitor and benchmark the healthiness of food environments globally. In order to assess the impact of food environments on population diets, it is necessary to monitor population diet quality between countries and over time. This paper reviews existing data sources suitable for monitoring population diet quality, and assesses their strengths and limitations. A step-wise framework is then proposed for monitoring population diet quality. Food balance sheets ( FBa S), household budget and expenditure surveys ( HBES) and food intake surveys are all suitable methods for assessing population diet quality. In the proposed 'minimal' approach, national trends of food and energy availability can be explored using FBa S. In the 'expanded' and 'optimal' approaches, the dietary share of ultra-processed products is measured as an indicator of energy-dense, nutrient-poor diets using HBES and food intake surveys, respectively. In addition, it is proposed that pre-defined diet quality indices are used to score diets, and some of those have been designed for application within all three monitoring approaches. However, in order to enhance the value of global efforts to monitor diet quality, data collection methods and diet quality indicators need further development work. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review was to examine the epidemiology of malpractice claims in primary care. Design: A computerised systematic literature search was conducted. Studies were included if they reported original data (≥10 cases) pertinent to malpractice claims, were based in primary care and were published in the English language. Data were synthesised using a narrative approach. Setting: Primary care. Participants: Malpractice claimants. Primary outcome: Malpractice claim (defined as a written demand for compensation for medical injury). We recorded: medical misadventure cited in claims, missed/delayed diagnoses cited in claims, outcome of claims, prevalence of claims and compensation awarded to claimants. Results: Of the 7152 articles retrieved by electronic search, a total of 34 studies met the inclusion criteria and were included in the narrative analysis. Twenty-eight studies presented data from medical indemnity malpractice claims databases and six studies presented survey data. Fifteen studies were based in the USA, nine in the UK, seven in Australia, one in Canada and two in France. The commonest medical misadventure resulting in claims was failure to or delay in diagnosis, which represented 26-63% of all claims across included studies. Common missed or delayed diagnoses included cancer and myocardial infarction in adults and meningitis in children. Medication error represented the second commonest domain representing 5.6-20% of all claims across included studies. The prevalence of malpractice claims in primary care varied across countries. In the USA and Australia when compared with other clinical disciplines, general practice ranked in the top five specialties accounting for the most claims, representing 7.6-20% of all claims. However, the majority of claims were successfully defended. Conclusions: This review of malpractice claims in primary care highlights diagnosis and medication error as areas to be prioritised in developing educational strategies and risk management systems. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this systematic review was to examine the epidemiology of malpractice claims in primary care. Design: A computerised systematic literature search was conducted. Studies were included if they reported original data (=10 cases) pertinent to malpractice claims, were based in primary care and were published in the English language. Data were synthesised using a narrative approach. Setting: Primary care. Participants: Malpractice claimants. Primary outcome: Malpractice claim (defined as a written demand for compensation for medical injury). We recorded: medical misadventure cited in claims, missed/delayed diagnoses cited in claims, outcome of claims, prevalence of claims and compensation awarded to claimants. Results: Of the 7152 articles retrieved by electronic search, a total of 34 studies met the inclusion criteria and were included in the narrative analysis. Twenty-eight studies presented data from medical indemnity malpractice claims databases and six studies presented survey data. Fifteen studies were based in the USA, nine in the UK, seven in Australia, one in Canada and two in France. The commonest medical misadventure resulting in claims was failure to or delay in diagnosis, which represented 26-63% of all claims across included studies. Common missed or delayed diagnoses included cancer and myocardial infarction in adults and meningitis in children. Medication error represented the second commonest domain representing 5.6-20% of all claims across included studies. The prevalence of malpractice claims in primary care varied across countries. In the USA and Australia when compared with other clinical disciplines, general practice ranked in the top five specialties accounting for the most claims, representing 7.6-20% of all claims. However, the majority of claims were successfully defended. Conclusions: This review of malpractice claims in primary care highlights diagnosis and medication error as areas to be prioritised in developing educational strategies and risk management systems. [ABSTRACT FROM AUTHOR]

Although systemic inflammation occurs in most pathological conditions that challenge the neural control of breathing, little is known concerning the impact of inflammation on respiratory motor plasticity. Here, we tested the hypothesis that low-grade systemic inflammation induced by lipopolysaccharide (LPS, 100 µg/kg ip; 3 and 24 h postinjection) elicits spinal inflammatory gene expression and attenuates a form of spinal, respiratory motor plasticity: phrenic long-term facilitation (pLTF) induced by acute intermittent hypoxia (AIH; 3, 5 min hypoxic episodes, 5 min intervals). pLTF was abolished 3 h (vehicle control: 67.1 ± 27.9% baseline; LPS: 3.7 ± 4.2%) and 24 h post-LPS injection (vehicle: 58.3 ± 17.1% baseline; LPS: 3.5 ± 4.3%). Pretreatment with the nonsteroidal anti-inflammatory drug ketoprofen (12.5 mg/kg ip) restored pLTF 24 h post-LPS (55.1 ± 12.3%). LPS increased inflammatory gene expression in the spleen and cervical spinal cord (homogenates and isolated microglia) 3 h postinjection; however, all molecules assessed had returned to baseline by 24 h postinjection. At 3 h post-LPS, cervical spinal iNOS and COX-2 mRNA were differentially increased in microglia and homogenates, suggesting differential contributions from spinal cells. Thus LPS-induced systemic inflammation impairs AIH-induced pLTF, even after measured inflammatory genes returned to normal. Since ketoprofen restores pLTF even without detectable inflammatory gene expression, "downstream" inflammatory molecules most likely impair pLTF. These findings have important implications for many disease states where acute systemic inflammation may undermine the capacity for compensatory respiratory plasticity. [ABSTRACT FROM AUTHOR]

Goldstein RB, Dawson DA, Smith SM, Grant BF. Antisocial behavioral syndromes and 3-year quality-of-life outcomes in United States adults. Objective: To examine 3-year quality-of-life (QOL) outcomes among United States adults with Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) antisocial personality disorder (ASPD), syndromal adult antisocial behavior without conduct disorder (CD) before age 15 [adulthood antisocial behavioral syndrome (AABS), not a DSM-IV diagnosis], or no antisocial behavioral syndrome at baseline. Method: Face-to-face interviews ( n = 34 653). Psychiatric disorders were assessed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule - DSM-IV Version. Health-related QOL was assessed using the Short-Form 12-Item Health Survey, version 2 (SF-12 v2). Other outcomes included past-year Perceived Stress Scale-4 (PSS-4) scores, employment, receipt of Supplemental Security Income (SSI), welfare, and food stamps, and participation in social relationships. Results: Antisocial personality disorder and AABS predicted poorer employment, financial dependency, social relationship, and physical health outcomes. Relationships of antisociality to SSI and food stamp receipt and physical health scales were modified by baseline age. Both antisocial syndromes predicted higher PSS-4, AABS predicted lower SF-12 v2 Vitality, and ASPD predicted lower SF-12 v2 Social Functioning scores in women. Conclusion: Similar prediction of QOL by ASPD and AABS suggests limited utility of requiring CD before age 15 to diagnose ASPD. Findings underscore the need to improve prevention and treatment of antisocial syndromes. [ABSTRACT FROM AUTHOR]

Background/Objectives:Adults often misreport dietary intake; the magnitude varies by the methods used to assess diet and classify participants. The objective was to quantify the accuracy of the Goldberg method for categorizing misreporters on a food frequency questionnaire (FFQ) and two 24-h recalls (24HRs).Subjects/Methods:We compared the Goldberg method, which uses an equation to predict total energy expenditure (TEE), with a criterion method that uses doubly labeled water (DLW), in a study of 451 men and women. Underreporting was classified using recommended cut points and calculated values. Sensitivity and specificity, positive predictive value (PPV) and negative predictive value and the area under the receiver operating characteristic curve (AUC) were calculated. Predictive models of underreporting were contrasted for the Goldberg and DLW methods.Results:AUCs were 0.974 and 0.972 on the FFQ, and 0.961 and 0.938 on the 24HR for men and women, respectively. The sensitivity of the Goldberg method was higher for the FFQ (92%) than the 24HR (50%); specificity was higher for the 24HR (99%) than the FFQ (88%); PPV was high for the 24HR (92%) and FFQ (88%). Simulation studies indicate attenuation in odds ratio estimates and reduction of power in predictive models.Conclusions:Although use of the Goldberg method may lead to bias and reduction in power in predictive models of underreporting, the method has high predictive value for both the FFQ and the 24HR. Thus, in the absence of objective measures of TEE or physical activity, the Goldberg method is a reasonable approach to characterize underreporting. [ABSTRACT FROM AUTHOR]

An electron spin resonance (ESR) study of the effects of pulverization on non-irradiated crystalline sugar was performed. It indicated that the crystalline sugar before being ground did not give any ESR signal but an ESR signal was found in pulverized sugar. These results implied that free radicals were produced by pulverization. Moreover, the free radical density increased as the particle size decreased. From high-performance liquid chromatography analysis and the ESR spectrum of non-irradiated powdered sucrose, it can be inferred that the pulverization-induced free radical in sugar is a sucrose radical. Recently, many researchers have reported that sugar irradiated with 60Co γ-rays at different doses produced stable sucrose radicals. This may imply that the process of sucrose radical formation by mechanical stress is similar to that for irradiation. [ABSTRACT FROM AUTHOR]

Infection with the intracellular protozoan parasite Toxoplasma gondii ( T. gondii) causes health problems to both humans and livestock and has a large economic impact worldwide. The immune response in sheep following infection with T. gondii was evaluated using six different combinations of plasmid DNA, recombinant antigen and adjuvant. Sheep were generally vaccinated twice by intramuscular injection with plasmid DNA containing gene sequences for either the surface antigen (SAG1) or the rhoptry protein (ROP1) of T. gondii. Two of the groups injected with plasmid DNA SAG1 were boosted with recombinant protein (SAG1). We investigated the efficacy of including oligodeoxynucleotides (ODN) that contain CG motifs (CpG) and the gene coding for ovine granulocyte-macrophage colony stimulating factor (GM-CSF) as potential adjuvants. Administration of the plasmid encoding the ROP1 gene significantly enhanced both IFN-γ production from peripheral blood cells when cultured in vitro with Toxoplasma antigen, and ROP1-specific IgG1 and IgG2 antibody levels present in serum. However, injection with SAG1 did not stimulate IFN-γ production. These results indicate the potential of ROP1, given as plasmid DNA, as a potential vaccine candidate to protect sheep against T. gondii infection. [ABSTRACT FROM AUTHOR]

Background: Despite frequent clinical use, information about the pharmacokinetics and efficacy of pantoprazole in camelids is not available. Objectives: To examine the pharmacokinetics of both IV and SC pantoprazole and to determine whether pantoprazole administration would increase 3rd compartment pH in alpacas. Animals: Six healthy adult alpacas. Methods: Alpacas were fitted with a 3rd compartment cannula for measuring gastric pH. After recovery, alpacas received 1 mg/kg pantoprazole IV, q24h for 3 days or 2 mg/kg SC q24h for 3 days. Alpacas received both IV and SC pantoprazole, with a minimum of 3 weeks between treatments. Third compartment pH was recorded and plasma samples were taken for pharmacokinetic analysis. Results: Pantoprazole induced a slow but sustained increase in 3rd compartment pH when given by both the IV and SC routes. Third compartment pH was significantly increased as compared with baseline values (1.81 ± 0.7; mean ± SD) at 24 (2.47 ± 0.8), 48 (3.53 ± 1.0) and 72 hours (4.03 ± 1.3) after daily IV administration of pantoprazole. Third compartment pH increased from 1.73 ± 0.6 at baseline to 3.05 ± 1.1, 4.02 ± 1.4, and 3.61 ± 1.6 at 24, 48, and 72 hours after SC administration, respectively. Pharmacokinetic analysis demonstrated that pantoprazole had a short elimination half-life (0.47 + 0.06 h) and a high clearance rate (12.2 ± 2.9 mL/kg/min) after both IV and SC administration. Conclusions and Clinical Relevance: Based on the results of this study, pantoprazole represents a safe and effective drug for increasing 3rd compartment pH in camelids. Either IV or SC administration is likely to be an effective treatment for gastric ulcers. [ABSTRACT FROM AUTHOR]