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Background Treatment of established depression is the dominant approach to care of older adults, but prevention holds much promise. Self-help interventions are a feasible preventive approach, since they are scalable and low cost. There are few trials in this area. Behavioral Activation (BA) is a credible candidate psychological approach, which has been shown to work in therapist led care but not been trialled in a self-help form. Aim To test the effectiveness of an unguided self-help intervention based on BA for older adults. Methods We compared a self-help intervention based on BA for older people (n = 172) to usual care (n = 160) in a pragmatic randomized controlled trial. Outcomes were depression status and severity (PHQ9) and health related quality of life (SF12). The primary timepoint of the primary outcome was depression at 4 months, with longer term follow up at 12 months to test sustained impact of the primary outcome. Results At 4 months adjusted PHQ-9 scores for BA self-help were 0.79 lower (95% CI: -1.70 to 0.13; p = 0.09) and the proportion of participants with case-level depression was significantly reduced (BA 31/137 (22.6%) versus usual care 41/141 (29.1%); Odds Ratio 0.48; 95% CI: 0.26–0.92; p = 0.03). There was no PHQ-9 difference at 12 months or for health related quality of life at any point (4 or 12 months). Discussion Self-help using BA for older people at risk of depression is a feasible and scalable intervention with potential short-term benefits in preventing depression.

Background Previous studies have identified functional brain abnormalities in pediatric posttraumatic stress disorder (pPTSD) suggesting altered frontoparietal-subcortical function during emotion processing. However, little is known about how the brain functionally changes over time in recovery versus the persistence of pPTSD. Methods This longitudinal study recruited 23 youth with PTSD and 28 typically developing (TD) youth (ages: 8.07-17.99). Within the PTSD group, nine remitted by the 1-year follow-up (Remit) while the remaining 14 persisted (PTSD). At each visit, youth completed an emotional processing task in which they viewed threat and neutral images during functional magnetic resonance imaging (fMRI). Voxelwise activation analyses using linear mixed-effects regression were conducted using a group (TD, Remit, PTSD) by time (baseline, follow-up) by valence (threat, neutral) design. Based on activation findings, a subsequent analysis of hippocampal functional connectivity was performed using a similar model. Results PTSD youth showed significantly increasing hippocampal activation to threatening images compared to TD youth, while the Remit group showed more similar patterns to TD youth. Subsequent hippocampal functional connectivity analyses reveal the Remit group showed increasing functional connectivity between the hippocampus and visual cortex (V4) while viewing threat stimuli. Conclusions These findings represent one of the first preliminary reports of functional brain substrates of persistence and remission in pPTSD. Notably, increased hippocampal activation to threat and decreased connectivity in the hippocampal-V4 network over time may contribute to persistence in pPTSD. These findings suggest potential biomarkers that could be utilized to advance the treatment of pediatric PTSD.

Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström macroglobulinemia (WM). The autoimmune disorders are primarily mediated by autoimmune monoclonal gammopathy, but drug-induced hemolysis should also be considered. Herein, we presented the case of a 63-year-old female WM patient complicated with ITP, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1–2×109/L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WM-related. Given the effects of ibrutinib in controlling WM, secondary AITP and AIHA, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis relieved three days after eltrombopag withdrawal. This is the first report on eltrombopag-induced AIHA in the management of WM-associated ITP.

Part‐MOT, a one‐stage anchor‐free architecture which unifies the object identification representation and detection in one task for visual object tracking is presented. For object representation, a position relevant feature is obtained using the center‐ness information, which takes advantage of the anchor‐free ideal to encode the feature map as the instance‐aware embedding. To adapt to the object's movement, the clustering‐based method to get the global instance feature is introduced. This enables this approach more robust to make better tracking decisions. Part‐MOT achieves the state‐of‐the‐art performance on public datasets, with especially strong results for object deformation and movement changes.

In order to improve the infrared detection and discrimination ability of the smart munition to the dynamic armor target under the complex background, the multi-line array infrared detection system is established based on the combination of the single unit infrared detector. The surface dimension features of ground armored targets are identified by size calculating solution algorithm. The signal response value and the value of size calculating are identified by the method of fuzzy recognition to make the fuzzy classification judgment for armored target. According to the characteristics of the target signal, a custom threshold de-noising function is proposed to solve the problem of signal preprocessing. The multi-line array infrared detection can complete the scanning detection in a large area in a short time with the characteristics of smart munition in the steady-state scanning stage. The method solves the disadvantages of wide scanning interval and low detection probability of single unit infrared detection. By reducing the scanning interval, the number of random rendezvous in the infrared feature area of the upper surface is increased, the accuracy of the size calculating is guaranteed. The experiments results show that in the fuzzy recognition method, the size calculating is introduced as the feature operator, which can improve the recognition ability of the ground armor target with different shape size.

Aims A pragmatic multicentre randomized controlled trial, UK FROzen Shoulder Trial (UK FROST), was conducted in the UK NHS comparing the cost-effectiveness of commonly used treatments for adults with primary frozen shoulder in secondary care. Methods A cost utility analysis from the NHS perspective was performed. Differences between manipulation under anaesthesia (MUA), arthroscopic capsular release (ACR), and early structured physiotherapy plus steroid injection (ESP) in costs (2018 GBP price base) and quality adjusted life years (QALYs) at one year were used to estimate the cost-effectiveness of the treatments using regression methods. Results ACR was £1,734 more costly than ESP ((95% confidence intervals (CIs) £1,529 to £1,938)) and £1,457 more costly than MUA (95% CI £1,283 to £1,632). MUA was £276 (95% CI £66 to £487) more expensive than ESP. Overall, ACR had worse QALYs compared with MUA (-0.0293; 95% CI -0.0616 to 0.0030) and MUA had better QALYs compared with ESP (0.0396; 95% CI -0.0008 to 0.0800). At a £20,000 per QALY willingness-to-pay threshold, MUA had the highest probability of being cost-effective (0.8632) then ESP (0.1366) and ACR (0.0002). The results were robust to sensitivity analyses. Conclusion While ESP was less costly, MUA was the most cost-effective option. ACR was not cost-effective. Cite this article: Bone Jt Open 2021;2(8):685–695.

BackgroundScaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased.ObjectiveTo compare the clinical effectiveness and cost-effectiveness of surgical fixation with cast treatment and early fixation in adults with scaphoid waist fractures that fail to unite.DesignMulticentre, pragmatic, open-label, parallel two-arm randomised controlled trial with an economic evaluation and a nested qualitative study.SettingOrthopaedic departments of 31 hospitals in England and Wales recruited from July 2013, with final follow-up in September 2017.ParticipantsAdults (aged ≥ 16 years) presenting within 2 weeks of injury with a clear, bicortical fracture of the scaphoid waist on plain radiographs.InterventionsEarly surgical fixation using Conformité Européenne-marked headless compression screws. Below-elbow cast immobilisation for 6–10 weeks and urgent fixation of confirmed non-union.Main outcome measuresThe primary outcome and end point was the Patient-Rated Wrist Evaluation total score at 52 weeks, with a clinically relevant difference of 6 points. Secondary outcomes included Patient-Rated Wrist Evaluation pain and function subscales, Short Form questionnaire 12-items, bone union, range of movement, grip strength, complications and return to work.ResultsThe mean age of 439 participants was 33 years; 363 participants were male (83%) and 269 participants had an undisplaced fracture (61%). The primary analysis was on 408 participants with valid Patient-Rated Wrist Evaluation outcome data for at least one post-randomisation time point (surgery,n = 203 of 219; cast,n = 205 of 220). There was no clinically relevant difference in the Patient-Rated Wrist Evaluation total score at 52 weeks: the mean score in the cast group was 14.0 (95% confidence interval 11.3 to 16.6) and in the surgery group was 11.9 (95% confidence interval 9.2 to 14.5), with an adjusted mean difference of –2.1 in favour of surgery (95% confidence interval –5.8 to 1.6;p = 0.27). The non-union rate was low (surgery group,n = 1; cast group,n = 4). Eight participants in the surgery group had a total of 11 reoperations and one participant in the cast group required a reoperation for non-union. The base-case economic analysis at 52 weeks found that surgery cost £1295 per patient more (95% confidence interval £1084 to £1504) than cast treatment. The base-case analysis of a lifetime-extrapolated model confirmed that the cast treatment pathway was more cost-effective. The nested qualitative study identified patients’ desire to have a ‘sense of recovering’, which surgeons should address at the outset.LimitationThere were 17 participants who had initial cast treatment and surgery for confirmed non-union, which in 14 cases was within 6 months from randomisation and in three cases was after 6 months. Three of the four participants in the cast group who had a non-union at 52 weeks were not offered surgery.ConclusionsAdult patients with an undisplaced or minimally displaced scaphoid waist fracture should have cast immobilisation and suspected non-unions immediately confirmed and urgently fixed. Patients should be followed up at 5 years to investigate the effect of partial union, degenerative arthritis, malunion and screw problems on their quality of life.Trial registrationCurrent Controlled Trials ISRCTN67901257.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 24, No. 52. See the NIHR Journals Library website for further project information.

Background\ud Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less.\ud Methods\ud This pragmatic, parallel-group, multicentre, open-label, two-arm, randomised superiority trial included adults (aged 16 years or older) who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear bicortical fracture of the scaphoid waist on radiographs. An independent remote randomisation service used a computer-generated allocation sequence with randomly varying block sizes to randomly assign participants (1:1) to receive either early surgical fixation (surgery group) or below-elbow cast immobilisation followed by immediate fixation if non-union of the fracture was confirmed (cast immobilisation group). Randomisation was stratified by whether or not there was displacement of either a step or a gap of 1–2 mm inclusive on any radiographic view. The primary outcome was the total patient-rated wrist evaluation (PRWE) score at 52 weeks after randomisation, and it was analysed on an available case intention-to-treat basis. This trial is registered with the ISRCTN registry, ISRCTN67901257, and is no longer recruiting, but long-term follow-up is ongoing.\ud Findings\ud Between July 23, 2013, and July 26, 2016, 439 (42%) of 1047 assessed patients (mean age 33 years; 363 [83%] men) were randomly assigned to the surgery group (n=219) or to the cast immobilisation group (n=220). Of these, 408 (93%) participants were included in the primary analysis (203 participants in the surgery group and 205 participants in the cast immobilisation group). 16 participants in the surgery group and 15 participants in the cast immobilisation group were excluded because of either withdrawal, no response, or no follow-up data at 6, 12, 26, or 52 weeks. There was no significant difference in mean PRWE scores at 52 weeks between the surgery group (adjusted mean 11·9 [95% CI 9·2–14·5]) and the cast immobilisation group (14·0 [11·3 to 16·6]; adjusted mean difference −2·1 [95% CI −5·8 to 1·6], p=0·27). More participants in the surgery group (31 [14%] of 219 participants) had a potentially serious complication from surgery than in the cast immobilisation group (three [1%] of 220 participants), but fewer participants in the surgery group (five [2%]) had cast-related complications than in the cast immobilisation group (40 [18%]). The number of participants who had a medical complication was similar between the two groups (four [2%] in the surgery group and five [2%] in the cast immobilisation group).\ud Interpretation\ud Adult patients with scaphoid waist fractures displaced by 2 mm or less should have initial cast immobilisation, and any suspected non-unions should be confirmed and immediately fixed with surgery. This treatment strategy will help to avoid the risks of surgery and mostly limit the use of surgery to fixing fractures that fail to unite.\ud Funding\ud National Institute for Health Research Health Technology Assessment Programme.

As artificial intelligence (AI) is enabling the automation of many facets of management and is increasingly used in a wide range of strategic tasks, it is necessary to better understand its relevance for strategic management. However, research on the interplay of AI and strategic management is unbalanced and lacks a coherent structure due to its multidisciplinarity. This article contributes to the emerging academic discussion by systematically reviewing and categorizing the substantial amount of research that has been conducted since the first article in the field was published in 1979. Furthermore, it introduces a comprehensive framework that integrates and synthesizes existing concepts. The framework displays the structure of the research field by classifying 58 relevant articles into two research scopes: condition-oriented research, which explores antecedents for leveraging the use of AI in strategic management, and outcome-oriented research, which studies the consequences of AI in strategic management at both the individual and the organizational level. Given the exponential potential of AI to reshape the field in its current form and the need for a realistic assessment of its impact, this review proposes promising research avenues for studying the quantifiable effects of the interplay of AI and strategic management based on the developed framework.

Background/Aims: There is growing interest in the use of adaptive designs to improve the efficiency of clinical trials. We apply a Bayesian decision-theoretic model of a sequential experiment using cost and outcome data from the ProFHER pragmatic trial. We assess the model’s potential for delivering value-based research. Methods: Using parameter values estimated from the ProFHER pragmatic trial, including the costs of carrying out the trial, we establish when the trial could have stopped, had the model’s value-based stopping rule been used. We use a bootstrap analysis and simulation study to assess a range of operating characteristics, which we compare with a fixed sample size design which does not allow for early stopping. Results: We estimate that application of the model could have stopped the ProFHER trial early, reducing the sample size by about 14%, saving about 5% of the research budget and resulting in a technology recommendation which was the same as that of the trial. The bootstrap analysis suggests that the expected sample size would have been 38% lower, saving around 13% of the research budget, with a probability of 0.92 of making the same technology recommendation decision. It also shows a large degree of variability in the trial’s sample size. Conclusions: Benefits to trial cost stewardship may be achieved by monitoring trial data as they accumulate and using a stopping rule which balances the benefit of obtaining more information through continued recruitment with the cost of obtaining that information. We present recommendations for further research investigating the application of value-based sequential designs.

Background Dupuytren’s contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery—collagenase clostridium histolyticum (collagenase)—is better than a placebo in the treatment of Dupuytren’s contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren’s intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap. Methods/design The DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy). We aim to recruit 710 adult participants with Dupuytren’s contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed. An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants’ experiences and preferences of the treatments. Discussion The DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren’s contracture. Trial registration Clinical.Trials.gov ISRCTN18254597. Registered on April 11, 2017.

AimsThis systematic review places a recently completed multi-centre randomised controlled trial (RCT) UK FROST, in the context of existing randomised evidence for the management of primary frozen shoulder. UK FROST compared the effectiveness of pre-specified physiotherapy techniques with a steroid injection (PTSI), manipulation under anaesthesia (MUA) with a steroid injection and arthroscopic capsular release (ACR). This review updates a 2012 review focusing on the effectiveness of MUA, ACR, hydrodilatation, and PTSI. MethodsMEDLINE, Embase, PEDro, Science Citation Index, Clinicaltrials.gov, CENTRAL and WHO International Clinical Trials Registry were searched up-to December 2018. Reference lists of included studies were screened. No language restrictions applied. Eligible studies were RCTs comparing the effectiveness of MUA, ACR, PTSI and hydrodilatation against each other or supportive care or no treatment for the management of primary frozen shoulder. ResultsNine RCTs were included. The primary outcome of patient reported shoulder function at long-term follow-up (>6 months and ≤ 12 months) was reported for five treatment comparisons across four studies. Standardised mean difference (SMD) were: ACR vs MUA: 0.21 (95% CI: 0.00 to 0.42), ACR vs supportive care: -0.13 (95% CI: -1.10 to 0.83), and ACR vs PTSI:0.33 (95% CI: 0.07 to 0.59) and 0.25 (95% CI: -0.34 to 0.85) all favouring ACR; MUA vs Supportive care: 0 (95% CI: -0.44 to 0.44) not favouring either; and MUA vs PTSI: 0.12 (95% CI: -0.14 to 0.37) favouring MUA. None of these differences met the threshold of clinical significance agreed for the UK FROST and most confidence intervals included zero. ConclusionThe findings from a recent multi-centre RCT provided the strongest evidence that, when compared with each other, neither PTSI, MUA nor ACR are clinically superior. Evidence from smaller RCTs did not change this conclusion. Hydrodilatation’s effectiveness based on four RCTs was inconclusive and remains an evidence gap. Where does this fit in the literature?•There were few high quality and adequately powered randomised studies that evaluated key treatment choices in the management of patients with primary frozen shoulder.•UK FROST has addressed this and provided the strongest evidence that when compared with each other neither PTSI, MUA nor ACR are clinically superior. Evidence from smaller RCTs did not change this conclusion.•There is an evidence gap suggesting the need for a rigorously designed and adequately powered RCT to evaluate the comparative effectiveness of hydrodilatation.

Summary Integrating nutrition communication in agricultural intervention programs aimed at increased food availability and accessibility in resource-poor areas is crucial. To enhance the sustainability and scalability of nutrition communication, the present study piloted the approach of ‘nutrition integrated agricultural extension’ and tested nutrition-related outcomes with two types of nutrition messages (specific vs. sensitive) and two delivery channels (public sector vs. private sector). The study intervention comprised (i) vegetable seed kit distribution, (ii) ongoing agricultural extension activities by public or private sectors and (iii) nutrition communication with two different messages. The intervention was tested with three treatment arms and reached 454 farmers (>65% female) in rural Kakamega County, Western Kenya. Pre-/post-surveys measured outcome variables focused on farmers’ nutrition-related knowledge, attitudes and practices in vegetable production and consumption, and household dietary diversity score. Results showed that all treatments increased nutrition knowledge (p

Infants exposed to Zika virus (ZIKV) prenatally may develop birth defects, developmental deficits, or remain asymptomatic. It is unclear why some infants are more affected than others, although enhancement of maternal ZIKV infection via immunity to an antigenically similar virus, dengue virus (DENV), may play a role. We hypothesized that DENV immunity may worsen prenatal ZIKV infection and developmental deficits in offspring. We utilized a translational macaque model to examine how maternal DENV immunity influences ZIKV-exposed infant macaque neurodevelopment in the first month of life. We inoculated eight macaques with prior DENV infection with ZIKV, five macaques with ZIKV, and four macaques with saline. DENV/ZIKV-exposed infants had significantly worse visual orientation skills than ZIKV-exposed infants whose mothers were DENV-naive, with no differences in motor, sensory or state control development. ZIKV infection characteristics and pregnancy outcomes did not individually differ between dams with and without DENV immunity, but when multiple factors were combined in a multivariate model, maternal DENV immunity combined with ZIKV infection characteristics and pregnancy parameters predicted select developmental outcomes. We demonstrate that maternal DENV immunity exacerbates visual orientation and tracking deficits in ZIKV-exposed infant macaques, suggesting that human studies should evaluate how maternal DENV immunity impacts long-term neurodevelopment.

BackgroundThe faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme.AimTo determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC.Design and settingPatients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation.MethodThe diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results.ResultsIn total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively.ConclusionFIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.

Background: Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström Macroglobulinemia (WM). The cause of AIHA should be carefully distinguished during the disease management. Case Presentation: A 63-year-old female WM patient complicated with thrombocytopenia, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1-2×109/L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WM-related. Given the effects of ibrutinib in controlling WM, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis alleviated within three days after eltrombopag withdrawal. Conclusion: This is the first report on eltrombopag-induced AIHA, and we should always keep in mind of the drug induced hemolysis even in disorders with autoimmune background.

In dynamic scene monocular visual SLAM, it is important to recognize static object imaging features for mapping. The optical flow of noise and the object moving in the same orientations would have the same orientations of static feature for two frames image, that would disturb static feature point recognition. Because the translational motion optical flow orientations method judges with optical flow of single feature point and translational motion orientations, it is not reliable for static feature point recognition. Therefore, a 3D motion segmentation combined for static object imaging features recognition is proposed, which clusters the same optical flow of feature points in 3D motion subspace, including orientations and amplitude of translation and rotation. The simulation results show that the proposed static object imaging features recognition method improves the recognition correct rate and reliability of static features. So, it is effective for static object imaging features recognition in dynamic scene mapping.

Volatile organic compounds (VOCs) have an important influence on the formation of photochemical smog and secondary organic aerosols in the atmosphere. In this paper, we investigated 104 VOCs in Heshan from 22 October to 22 November 2014 to identify the sources and abatement mechanisms of VOCs in southern China. Weather conditions, species correlations, daytime and nighttime abatement mechanisms, secondary pollutant transformations, air-mass origins and source apportionments were studied. During the observation period, the average concentration of VOCs in the atmosphere of Heshan was 61.0 ± 35.5 ppbv, and the wind speed played a pivotal role in the diffusion and dilution of VOCs. The study on the rates of OH, O3 and NO3 radicals found that alkenes, aromatics, hydrocarbons and carbonyl compounds were the most active volatile organic compounds in Heshan. For alkanes, alkynes, and aromatics, removal is determined by their reactions with OH radicals. For highly reactive alkenes and styrene, nighttime removal via O3 and NO3 radicals was also significant. The backward-trajectory cluster analysis of air masses indicated that pollution mainly derived from the east-northeast. The paint solvent usage, paint solvent usage + liquefied petroleum gas (LPG) usage, biomass burning, coal burning + industrial combustion sources, gasoline vehicle exhaust, diesel vehicle exhaust, industrial sources, and fuel evaporation (gasoline) contributed 11%, 22%, 13%, 17%, 12%, 8%, 11%, and 6% to VOCs during the observation period, respectively.

Background Prior studies of pediatric posttraumatic stress disorder (PTSD) have reported cross-sectional and age-related structural and functional brain abnormalities in networks associated with cognitive, affective, and self-referential processing. However, no reported studies have comprehensively examined longitudinal gray matter development and its intrinsic functional correlates in pediatric PTSD. Methods Twenty-seven youths with PTSD and 21 nontraumatized typically developing (TD) youths were assessed at baseline and 1-year follow-up. At each visit, youths underwent structural magnetic resonance imaging and resting-state functional magnetic resonance imaging. Regions with volumetric abnormalities in whole-brain structural analyses were identified and used as seeds in exploratory intrinsic connectivity analyses. Results Youths with PTSD exhibited sustained reductions in gray matter volume (GMV) in right ventromedial prefrontal cortex (PFC) and bilateral ventrolateral PFC. Group-by-time analyses revealed aberrant longitudinal development in dorsolateral PFC, where typically developing youths exhibited normative decreases in GMV between baseline and follow-up, and youths with PTSD showed increases in GMV. Using these regions as seeds, patients with PTSD exhibited atypical longitudinal decreases in intrinsic PFC–amygdala and PFC–hippocampus connectivity, in contrast to increases in typically developing youths. Specifically, youths with PTSD showed decreasing ventromedial PFC–amygdala connectivity as well as decreasing ventrolateral PFC–hippocampus connectivity over time. Notably, volumetric abnormalities in ventromedial PFC and ventrolateral PFC were predictive of symptom severity. Conclusions These findings represent novel longitudinal volumetric and connectivity changes in pediatric PTSD. Atypical prefrontal GMV and prefrontal-amygdala/hippocampus development may underlie persistence of PTSD in youths and could serve as future therapeutic targets.

We design a novel phase real-time microscope camera (PhaseRMiC) for live cell phase imaging. PhaseRMiC has a simple and cost-effective configuration only consisting of a beam splitter and a board-level camera with two CMOS imaging chips. Moreover, integrated with 3-D printed structures, PhaseRMiC has a compact size of 136×91×60 mm3, comparable to many commercial microscope cameras, and can be directly connected to the microscope side port. Additionally, PhaseRMiC can be well adopted in real-time phase imaging proved with satisfied accuracy, good stability and large field of view. Considering its compact and cost-effective device design as well as real-time phase imaging capability, PhaseRMiC is a preferred solution for live cell imaging.

Ding Ye,1 Bin Liu,1 Zhixing He,2 Lin Huang,2 Yu Qian,1 Keding Shao,2 Chengping Wen,2 Yingying Mao1 1Department of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Institute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaCorrespondence: Yingying MaoDepartment of Epidemiology and Biostatistics, Zhejiang Chinese Medical University School of Public Health, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8661-3536Email myy@zcmu.edu.cnChengping WenInstitute of Basic Research in Clinical Medicine, Zhejiang Chinese Medical University School of Basic Medical Sciences, Hangzhou, Zhejiang, 310053, People’s Republic of ChinaTel +86-571-8663-3377Email wengcp@163.comObjective: To investigate the potential causal associations of circulating levels of growth differentiation factor 15 (GDF-15) with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) using a Mendelian randomization (MR) design.Methods: A genome-wide association study (GWAS) of GDF-15 among 5,440 individuals of European ancestry was used to identify genetic instruments. Summary statistics of SLE, RA and IBD were obtained from publicly available GWASs. We conducted an MR study using the inverse-variance weighted (IVW) method, supplemented with simple-median and weighted-median methods. Cochran Q test and MR-Egger regression were used to detect potential heterogeneity and directional pleiotropy. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.Results: We found that genetically predicted high circulating GDF-15 levels were associated with a decreased risk of SLE (OR 0.80, 95% CI 0.68– 0.92 by IVW), with similar results in sensitivity analyses. In replication analysis using summary data from another SLE GWAS, the results were consistent (OR 0.82, 95% CI 0.71– 0.93 by IVW). Moreover, no evidence of heterogeneity or pleiotropy was detected. However, genetically determined circulating levels of GDF-15 were not associated with risk of RA or IBD in the primary analysis and subsequent sensitivity analyses.Conclusions: Our study suggested an inverse association between circulating GDF-15 levels and risk of SLE, and further studies are warranted to elucidate the underlying biological mechanisms. There was limited evidence supporting a causal association of circulating GDF-15 levels with risk of RA and IBD.Keywords: growth differentiation factor 15, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Mendelian randomization, single nucleotide polymorphism

Objective Observational epidemiologic studies have reported a relationship between selenium status and risk for autoimmune diseases. However, the associations are susceptible to confounding or reverse causality. Thus, the aim of this study was to investigate the potential causal associations of selenium concentrations with the risk for common autoimmune diseases using a two-sample Mendelian randomization (MR) design. Methods A meta-analysis of genome-wide association studies (GWASs) of selenium among 9639 individuals of European ancestry was used to identify genetic instruments. Summary statistics of systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease were obtained from publicly available GWASs, respectively. We conducted MR study using the inverse-variance weighted method, supplemented with weighted median and likelihood-based methods as sensitivity analysis. Cochran Q test and MR-Egger regression were used to detect heterogeneity and potential directional pleiotropy. MR-Pleiotropy RESidual Sum and Outlier test was used to identify outlier single-nucleotide polymorphisms. Results Genetically predicted high selenium level was associated with a decreased risk for SLE (odds ratio, 0.85; 95% confidence interval, 0.77–0.93; P = 0.001) per natural log-transformed selenium concentrations, with similar results in sensitivity analyses. No evidence of heterogeneity, pleiotropy, or outlier single-nucleotide polymorphisms were detected (all P > 0.05). However, genetically determined selenium concentrations may be not associated with risk for rheumatoid arthritis or inflammatory bowel disease in the primary analysis and subsequent sensitivity analyses. Conclusions The present study suggested a protective role of selenium on the risk for systemic lupus erythematosus. Further studies are warranted to elucidate the underlying mechanisms.

Aims A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients’ quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. Methods A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. Discussion The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150–163.

Ebola virus remains a global threat to public health and biosecurity, yet we still know relatively little about its pathogenesis and the complications that arise following recovery. With nearly 20,000 survivors from the 2013–2016 West African outbreak, as well as over 1,000 survivors of the recent outbreak in the DRC, we must consider the consequences of virus persistence and recrudescent disease, even if they are rare., Ebola virus (EBOV) is responsible for numerous devastating outbreaks throughout Africa, including the 2013–2016 West African outbreak as well as the two recent outbreaks in the Democratic Republic of the Congo (DRC), one of which is ongoing. Although EBOV disease (EVD) has typically been considered a highly lethal acute infection, increasing evidence suggests that the virus can persist in certain immune-privileged sites and occasionally lead to EVD recrudescence. Little is understood about the processes that contribute to EBOV persistence and recrudescence, in part because of the rarity of these phenomena but also because of the absence of an animal model that recapitulates them. Here, we describe a case of EBOV persistence associated with atypical EVD in a nonhuman primate (NHP) following inoculation with EBOV and treatment with an experimental monoclonal antibody cocktail. Although this animal exhibited only mild signs of acute EVD, it developed severe disease 2 weeks later and succumbed shortly thereafter. Viremia was undetectable at the time of death, despite abundant levels of viral RNA in most tissues, each of which appeared to harbor a distinct viral quasispecies. Remarkably, sequence analysis identified a single mutation in glycoprotein (GP) that not only resisted antibody-mediated neutralization but also increased viral growth kinetics and virulence. Overall, this report represents the most thoroughly characterized case of atypical EVD in an NHP described thus far, and it provides valuable insight into factors that may contribute to EBOV persistence and recrudescent disease.

Background: Recent findings in neuroimaging and epigenetics offer important insights into brain structures and biological pathways of altered gene expression associated with posttraumatic stress disorder (PTSD). However, it is unknown to what extent epigenetic mechanisms are associated with PTSD and its neurobiology in youth. Methods: In this study, we combined a methylome-wide association study and structural neuroimaging measures in a Dutch cohort of youths with PTSD (8–18 years of age). We aimed to replicate findings in a similar independent U.S. cohort. Results: We found significant methylome-wide associations for pediatric PTSD (false discovery rate p < .05) compared with non-PTSD control groups (traumatized and nontraumatized youths). Methylation differences on nine genes were replicated, including genes related to glucocorticoid functioning. In both cohorts, methylation on OLFM3 gene was further associated with anterior hippocampal volume. Conclusions: These findings point to molecular pathways involved in inflammation, stress response, and neuroplasticity as potential contributors to neural abnormalities and provide potentially unique biomarkers and treatment targets for pediatric PTSD.

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic, stigmatizing skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (ClinicalTrials.gov: NCT02894008) was an open-label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration, 30 months; range, 6–180 months). Patients received a single intramuscular vaccination of 1 × 1010 viral particles (v.p.; adults only) or 7.5 × 1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42–120 days follow-up. AmBisome was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole-blood transcriptomics and ELISpot. 7/23 patients (30.4%) monitored to study completion showed >90% clinical improvement, and 5/23 (21.7%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomized controlled trial to determine whether these clinical responses were vaccine-related and whether ChAd63-KH vaccine has clinical utility is underway., Graphical abstract, Post-kala-azar dermal leishmaniasis (PKDL) is a chronic parasitic disease with limited treatment options. Here, Musa and colleagues report on a phase IIa therapeutic trial of the adenoviral-vectored leishmaniasis vaccine ChAd63-KH. Single-dose vaccination with ChAd63-KH was safe and induced innate and T cell responses in Sudanese patients with PKDL.

With the development of new energy industry, it’s beneficial to analyze the characteristics of new energy which stabilize the operation of the power grid and economic dispatch. It’s more and more important to model the uncertainty of new energy. Although there are some probabilistic modeling methods based on real load data for wind power output, they are not accurate and have high computational complexity. In order to solve these problems, this paper proposes a source-charge probability distribution model based on variational autoencoder. The model uses deep learning techniques to perform variational autoencoder and probabilistic modeling for real-time wind power data. This unsupervised method can learn the characteristics of wind power data and generate new data based on the characteristics of the observation without the scene reduction process. It improves the efficiency and quality of scene generation.

The ability to read other people’s emotions among older people decline with age, which may result in weakened ability to detect deception. Microexpression is closely related to deception; and microexpression can be a valid cue to deception. Therefore, we hypothesized that there existed a positive correlation between microexpression recognition and deception detection in the older adults. To test the hypothesis, twenty-eight older adults (14 females, mean age=70 years, SD=6.2 years) were recruited for this study. They completed the tasks of the microexpression recognition and deception detection. The results showed that: (1) there was a positive correlation between fear macroexpression recognition and deception detection in the elderly (r=0.416, p =.028); (2) the ability of the elderly to detect truth (i.e., truth detection, mean accuracy=0.53) was significantly higher than the ability to detect deception (lie detection), t$(27)$=2.856, p=0.008; (3) there was significant main effect of type of emotional expressions$(F(2,25)$=11.721, p

BACKGROUND: Smoking cessation is important in patients with tuberculosis because it can reduce the high rates of treatment failure and mortality. We aimed to assess the effectiveness and safety of cystine as a smoking cessation aid in patients with tuberculosis in Bangladesh and Pakistan.; METHODS: We did a randomised, double-blind, placebo-controlled, trial at 32 health centres in Bangladesh and Pakistan. Eligible patients were adults (aged >18 years in Bangladesh; aged >15 years in Pakistan) with pulmonary tuberculosis diagnosed in the previous 4 weeks, who smoked tobacco on a daily basis and were willing to stop smoking. Patients were randomly assigned (1:1) to receive behavioural support plus either oral cytisine (9 mg on day 0, which was gradually reduced to 1·5 mg by day 25) or placebo for 25 days. Randomisation was done using pregenerated block randomisation lists, stratified by trial sites. Investigators, clinicians, and patients were masked to treatment allocation. The primary outcome was continuous abstinence at 6 months, defined as self-report (of not having used more than five cigarettes, bidis, a water pipe, or smokeless tobacco products since the quit date), confirmed biochemically by a breath carbon monoxide reading of less than 10 parts per million. Primary and safety analysis were done in the intention-to-treat population. This trial is registered with the International Standard Randomised Clinical Trial Registry, ISRCTN43811467, and enrolment is complete.; FINDINGS: Between June 6, 2017, and April 30, 2018, 2472 patients (1527 patients from Bangladesh; 945 patients from Pakistan) were enrolled and randomly assigned to receive cytisine (n=1239) or placebo (n=1233). At 6 months, 401 (32·4%) participants in the cytisine group and 366 (29·7%) participants in the placebo group had achieved continuous abstinence (risk difference 2·68%, 95% CI -0·96 to 6·33; relative risk 1·09, 95% CI 0·97 to 1·23, p=0·114). 53 (4·3%) of 1239 participants in the cytisine group and 46 (3·7%) of 1233 participants in the placebo group reported serious adverse events (94 events in the cytisine group and 90 events in the placebo group), which included 91 deaths (49 in the cytisine group and 42 in the placebo group). None of the adverse events were attributed to the study medication.; INTERPRETATION: Our findings do not support the addition of cytisine to brief behavioural support for the treatment of tobacco dependence in patients with tuberculosis.; FUNDING: European Union Horizon 2020 and Health Data Research UK.; TRANSLATIONS: For the Bengali and Urdu translations of the abstract see Supplementary Materials section. Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508. Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release). All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective. The National Institute for Health Research Health Technology Assessment programme. [Abstract copyright: Copyright © 2020 The Author(s). Publishedx by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.]

Post kala azar dermal leishmaniasis (PKDL) is a chronic, stigmatising skin condition occurring frequently after apparent clinical cure from visceral leishmaniasis. Given an urgent need for new treatments, we conducted a Phase IIa safety and immunogenicity trial of ChAd63-KH vaccine in Sudanese patients with persistent PKDL. LEISH2a (NCT02894008) was an open label three-phase clinical trial involving sixteen adult and eight adolescent patients with persistent PKDL (median duration 30 months; range 6 -180 months). Patients received a single intramuscular vaccination of 1×1010 viral particles (v.p.; adults only) or 7.5×1010 v.p. (adults and adolescents), with primary (safety) and secondary (clinical response and immunogenicity) endpoints evaluated over 42-120 days follow up. AmBisome® was provided to patients with significant remaining disease at their last visit. ChAd63-KH vaccine showed minimal adverse reactions in PKDL patients and induced potent innate and cell-mediated immune responses measured by whole blood transcriptomics and ELISpot. 7 patients (30.4%) monitored to study completion showed >90% clinical improvement and 6 (25%) showed partial improvement. A logistic regression model applied to blood transcriptomic data identified immune modules predictive of patients with >90% clinical improvement. A randomised controlled trial to determine whether these clinical responses were vaccine related and whether ChAd63-KH vaccine has clinical utility is underway.

Context: Vision rehabilitation (VR) services in England promote users’ health and wellbeing, and support all aspects of daily living through two dominant models: in-house and contracted-out VR services. The two models differ in terms of service delivery, but they share a common aim to enhance service users’ quality of life and reduce utilisation of social and health care services.Objective: This study investigated the cost-effectiveness of in-house versus contracted-out VR services.Methods: The analysis was performed from a social care perspective and a social and health care perspective. The analyses used data from a six-month follow-up observational study of VR users. Regression analysis was used to estimate differential outcomes and costs, taking user and local authority characteristics into account.Findings: At a cost-effectiveness threshold of £13,000 and £30,000 per QALY, in-house VR services have a high probability (greater than 90% vs. contracted-out VR services) of being cost-effective from a social care perspective. In-house VR services have a lower probability (lower than 25% vs. contracted-out VR services) of being cost-effective from a social and health care perspective.Limitations: Observational studies are prone to selection bias compared to randomised controlled trials due to confounding. We employed econometric techniques that control for several user and LA characteristics to reduce potential bias.Implications: Contracted-out VR services may be better value for money compared to in-house VR services in the context of integrated social and health care due to substantial healthcare resource savings.

Introduction Smoking has a negative impact on TB outcomes. We estimated the proportion of TB patients who smoke and are willing to quit in two high TB burden countries, Bangladesh and Pakistan. Methods A cross-sectional survey was conducted among TB patients to assess their eligibility and recruit them to a smoking cessation randomized controlled trial. Adults diagnosed with TB were recruited from 32 health facilities in Bangladesh and Pakistan. Data on smoking behaviour and willingness to quit were collected and analysed. Results In total, 13934 TB patients completed the survey between June 2017 and April 2018. The prevalence of smoking in these TB patients was estimated to be 22.5% (95% CI: 21.8, 23.2). Moreover, the prevalence of smoking in TB patient population was 8% (RR=1.49; 95% CI: 7.1–8.9; p

Intense pulsed light (IPL) is capable of entirely replacing thermal annealing (curing and contact formation) within back end processing of silicon heterojunction solar cells. In order to demonstrate this, full-size silicon heterojunction (SHJ) cells with IPL-processed screen-printed metal contacts are evaluated. Such cells reach conversion efficiencies of up to 23.0%. On average, IPL-annealed SHJ cells outperform their thermally treated pendants by 0.3-0.4% abs , in particular because of higher open-circuit voltages and fill factors. Moreover, IPL offers high throughput and low footprint. This results in a cost of ownership reduction potential of 6% rel compared to state-of-the-art thermal annealing.

Objectives The objective of this study was to assess whether timing of short messaging service (SMS) reminders improved postal questionnaire return rates from participants in a randomized controlled trial (RCT). Study Design and Setting A Study Within A Trial (SWAT) embedded in a multicenter RCT evaluating three treatments for the frozen shoulder. Participants who provided a mobile telephone number were randomized to either prenotification SMS on the day of the questionnaire mail-out or postnotification SMS 4 days after questionnaire mail-out for the 3-month follow-up. The primary outcome was the proportion of participants who returned a valid questionnaire. A systematic review was undertaken to identify other embedded trials to perform a meta-analysis. Results Of the 269 participants, 122/135 (90.4%) returned a valid questionnaire in the prenotification arm and 119/134 (88.8%) in the postnotification arm (difference of −1.6%; 95% CI of difference: −8.9%, 5.7%). There was no difference in time to response (HR = 1.04; 95% CI: 0.80 to 1.34) or need for additional reminders (OR = 0.71; 95% CI: 0.43 to 1.17). Meta-analysis of two RCTs showed no difference in response rates between prenotification and postnotification reminders (OR = 0.78 95% CI: 0.42 to 1.45). Conclusion Timing of SMS reminders did not improve response rates and time to response or affect the need for additional reminders.

Background: Printed participant information about randomised controlled trials is often long, technical and difficult to navigate. Improving information materials is possible through optimisation and user-testing, and may impact on participant understanding and rates of recruitment. Methods: A study within a trial (SWAT) was undertaken within the CASPER trial. Potential CASPER participants were randomised to receive either the standard trial information or revised information that had been optimised through information design and user testing. Results: A total of 11,531 patients were randomised in the SWAT. Rates of recruitment to the CASPER trial were 2.0% in the optimised information group and 1.9% in the standard information group (odds ratio 1.027; 95% CI 0.79 to 1.33; p=0.202). Conclusions: Participant information that had been optimised through information design and user testing did not result in any change to rate of recruitment to the host trial. Registration: ISRCTN ID ISRCTN02202951; registered on 3 June 2009.

Background Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? Methods The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years, The primary outcome is cotinine/anabasine-validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with SSS, quit rates at 4 weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention to treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case-study approach will identify opportunities to improve recruitment and learning for future implementation. Research questions include: what is the therapeutic efficacy of incentives; are incentives cost-effective; and what are the potential facilitators and barriers to implementing incentives in different parts of the UK? Discussion This phase III trial in Scotland, England and Northern Ireland follows a successful phase II trial in Glasgow, UK. The participating sites have diverse SSS that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective, this trial could demonstrate that financial incentives are effective and transferable to most UK SSS for pregnant women. Trial registration Current Controlled Trials, ISRCTN15236311. Registered on 9 October 2017.

AimsThe aim of this study was to explore whether time to surgery affects functional outcome in displaced proximal humeral fracturesMethodsA total of 250 patients presenting within three weeks of sustaining a displaced proximal humeral fracture involving the surgical neck were recruited at 32 acute NHS hospitals in the United Kingdom between September 2008 and April 2011. Of the 125 participants, 109 received surgery (fracture fixation or humeral head replacement) as per randomization. Data were included for 101 and 67 participants at six-month and five-year follow-up, respectively. Oxford Shoulder Scores (OSS) collected at six, 12, and 24 months and at three, four, and five years following randomization was plotted against time to surgery. Long-term recovery was explored by plotting six-month scores against five-year scores and agreement was illustrated with a Bland-Altman plot.ResultsThe mean time from initial trauma to surgery was 10.5 days (1 to 33). Earlier surgical intervention did not improve OSS throughout follow-up, nor when stratified by participant age (< 65 years vs ≥ 65 years) and fracture severity (one- and two-part vs three- and four-part fractures). Participants managed later than reported international averages (three days in the United States and Germany, eight days in the United Kingdom) did not have worse outcomes. At five-year follow-up, 50 participants (76%) had the same or improved OSS compared with six months (six-month mean OSS 35.8 (SD 10.0); five-year mean OSS 40.1 (SD 9.1); r = 0.613). A Bland-Altman plot demonstrated a positive mean difference (3.3 OSS points (SD 7.92)) with wide 95% limits of agreement (-12.2 and 18.8 points).ConclusionTiming of surgery did not affect OSS at any stage of follow-up, irrespective of age or fracture type. Most participants had maximum functional outcome at six months that was maintained at five years. These findings may help guide providers of trauma services on surgical prioritization. Cite this article: Bone Joint J 2020;102-B(1):33–41

The basic experimental data of traditional Chinese medicine are generally obtained by high-performance liquid chromatography and mass spectrometry. The data often show the characteristics of high dimensionality and few samples, and there are many irrelevant features and redundant features in the data, which bring challenges to the in-depth exploration of Chinese medicine material information. A hybrid feature selection method based on iterative approximate Markov blanket (CI_AMB) is proposed in the paper. The method uses the maximum information coefficient to measure the correlation between features and target variables and achieves the purpose of filtering irrelevant features according to the evaluation criteria, firstly. The iterative approximation Markov blanket strategy analyzes the redundancy between features and implements the elimination of redundant features and then selects an effective feature subset finally. Comparative experiments using traditional Chinese medicine material basic experimental data and UCI’s multiple public datasets show that the new method has a better advantage to select a small number of highly explanatory features, compared with Lasso, XGBoost, and the classic approximate Markov blanket method.

In recent years the growing popularity of Convolutional Neural Networks (CNNs) has driven the development of specialized hardware, so called Deep Learning Accelerators (DLAs). The large market for DLAs and the huge amount of papers published on DLA design show that there is currently no one-size-fits-all solution. Depending on the given optimization goals such as power consumption or performance, there may be several optimal solutions for each scenario. A commonly used method for finding these solutions as early as possible in the design cycle, is the employment of analytical models which try to describe a design by simple yet insightful and sufficiently accurate formulas. The main contribution of this work is the generic Analytical Model for AI accelerators (AMAIX) for the estimation of CNN inference performance on DLAs. It is based on the popular Roofline model. To show the validity of our approach, AMAIX was applied to the Nvidia Deep Learning Accelerator (NVDLA) as a case study using the AlexNet and LeNet CNNs as workloads. The resulting performance predictions were verified against an RTL emulation of the NVDLA using a Synopsys ZeBu Server-based hybrid prototype. AMAIX predicted the inference time of AlexNet and LeNet on the NVDLA with an accuracy of up to 88% and 98% respectively. Furthermore, this work shows how to use the obtained results for root-cause analysis and as a starting point for design space exploration.

Faecal calprotectin (FC) and the faecal immunochemical test for haemoglobin (FIT) are recommended for use in primary care where colorectal cancer (CRC) is not suspected.1 2 We are unclear how best to use these two biomarkers in younger patients where lower gastrointestinal symptoms are extremely common. Distinguishing irritable bowel syndrome from inflammatory bowel disease (IBD) from CRC on clinical grounds is often an uncertain exercise. Currently, there is no direct comparative evidence base on which to identify the optimal use of each biomarker. We undertook an illustrative comparison of the diagnostic accuracy of FC in a patient dataset at ‘low risk’ of CRC stratified by age and symptoms, and of FIT, from three existing published studies that included both CRC and IBD in their outcomes.3–11 From an existing dataset of patients using the York Faecal Calprotectin Care Pathway (YFCCP), we identified 1919 patients fulfilling National Institute for Health and Care Excellence (NICE) DG30 criteria. …

Female farmers are often overburdened with the multiple roles they assume in households, farming, childcare and the community. Horticultural projects that aim to improve nutrition and livelihoods usually address the women's domain of home gardens and vegetable farming. As a consequence, interventions tend to increase the workload of female farmers and run the risk of negatively affecting the well-being of women as well as the nutritional status of households. This paper explores gender challenges of horticultural projects using two case studies from Ethiopia and Madagascar, where an attempt is made to promote horticultural production in agroforestry systems without increasing the burden on already overstrained women farmers. Data were collected through ethnography, 42 gender-disaggregated focus group discussions and 25 in-depth interviews with smallholder farmers, as well as 19 key stakeholder interviews in four village sites in Oromia, Ethiopia, and two sites in south-eastern Madagascar. The do-no-harm framework was used as the conceptual framework. It identifies so-called connectors and dividers in households and communities to prevent “gender harms”, to offset the negative effects of interventions, and to develop mitigation strategies to improve project outcomes. Research results showed that many factors can become connectors or dividers depending on the project objectives and approach. In both locations, vital dividers for the project are the immense workload of women that prevents the expansion of vegetable cultivation and the low value that is attached to (indigenous) vegetable and fruit crops, especially by men, which does not match with their important role for diet and family nutrition. Other dividers are male-dominated extension services, the executive role of women in horticulture and low access to inputs. Mitigation strategies that should be developed can include territorial, technological and training solutions that aim to change behavior.

AI-augmented decision-making processes promise to transform strategic decisions around innovation management. However, despite a growing body of research on algorithmic management, very little is known about the behavioral effects of the AI-augmented decision-making process. This article utilizes a psychological perspective to research the interaction of artificial intelligence and human judgment, suggesting that AI-based advice affects human decision-making behavior and skews perceptions of decision outcomes. We present a vignette-based decision experiment involving 150 senior executives to examine the perception of AI-augmented decision-making at the individual level. In contrast to earlier research on algorithm aversion, we find that employing AI-based advisory systems positively affects choice behavior and amplifies decision quality perception. We further show how this overreliance on an AI-augmented decision-making process can be explained through both a higher degree of trust in the advisor and the attribution of a more structured process. This paper contributes to the emerging discussion as to the role of AI in management and the novel phenomenon of algorithm appreciation by investigating the interplay of human and artificial intelligence in strategic decision-making to show that AI-based advice is perceived as more trustworthy than human advice in an R&D investment context.

The laser ignition has been proposed for the realization of safe and reliable ignition of explosives. However, the high energy of laser ignition has seriously hindered its practical application. Therefore, it is of great significance to the wide application of laser ignition for developing a photosensitizer with good laser ignition performance under low laser energy. Herein, a free-standing graphene oxide (GO)/cyclotrimethylene trinitramine (RDX) composite film, known as GxRy (x: the mass of GO, y: the mass of RDX) composite film, was obtained to investigate the laser ignition performance. The results showed that the laser photothermal properties of GxRy composite films could be significantly improved by mixing GO with RDX. The temperature of G20R5 composite film could raise from 25 to 1040 °C under the pulsed laser irradiation (450 nm, 0.7 W), showing excellent photothermal properties. The high temperature rise of G20R5 film under laser irradiation might be due to the decomposition and combustion of RDX in the G20R5 film. The G20R5 composite film would be a promising laser photothermal conversion device for low initial energy photothermal ignition and provide a new idea for the preparation of photosensitizers with high laser photothermal properties.

ObjectiveTo compare the efficacy of modified treatments based on “kidney reinforcing” in the management of chronic aplastic anemia (CAA), and explore their advantages and specialties.MethodsOne hundred and eleven patients with CAA were randomly divided into three groups: kidney reinforcing alone (KA), “kidney reinforcing and Qi tonifying” (KQ), and “kidney reinforcing and blood circulation invigorating” (KC). Normal and positive control groups were also formed. All patients were treated for 6 months (two courses). Hemograms, Traditional Chinese Medicine (TCM) syndrome scores, and therapeutic effects were assessed, and changes in T-lymphocyte subsets, regulatory T cells and cytokines were detected.ResultsThe KQ and KC groups had lower TCM syndrome scores than the positive control group after 6 months (P < 0.05). The KQ group had a higher overall efficacy than the positive control group after 3 months (P < 0.05), while platelet counts increased in the KC group after 6 months (P < 0.05). CD3+T-lymphocyte ratios decreased only in the KQ group, while CD3 + CD4+ CD8− Tlymphocytes increased only in the KC group after 6 months (P < 0.05). Levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-2 and IL-6 decreased and levels of IL-4 and IL-10 increased in all treated groups after 6 months. Levels of IL-6 in the KQ and KC groups were lower than those in the positive control group (P < 0.05).ConclusionTreatments based on kidney reinforcing have a rebalancing effect on cytotoxic and T helper cells, and regulate expression of interferon-γ, IL-2, IL-6 and IL-4. KQ may be more effective in treating CAA, and KC may have an advantage in platelet recovery.

Background: An economic evaluation alongside the Hydroxychloroquine Effectiveness in Reducing symptoms of hand Osteoarthritis (HERO) trial was undertaken to assess the cost-effectiveness of hydroxychloroquine compared with placebo for symptomatic treatment of hand osteoarthritis for patients with at least moderate hand pain and inadequate response to current therapies. Methods: A trial-based cost–utility analysis was undertaken from the perspective of the UK National Health Service and Personal Social Services over a 12-month time horizon, using evidence from 248 participants included in the HERO trial, conducted in England. Patient-level data were collected prospectively over a 12-month period, using participant-completed questionnaires and investigator forms, to collect healthcare utilisation, costs and quality-adjusted life years (QALYs) using the EQ-5D-5L. The base-case analysis was conducted on an intention-to-treat basis and used multiple imputation methods to deal with missing data. Results were presented in terms of incremental cost-effectiveness ratios (incremental cost per QALY) and net health benefit, with uncertainty surrounding the findings explored using cost-effectiveness acceptability curves. Results: The base-case analysis estimated slightly lower costs on average (−£11.80; 95% confidence interval (CI) −£15.60 to −£8.00) and marginally fewer QALYs (−0.0052; 95% CI −0.0057 to −0.0047) for participants in the hydroxychloroquine group versus placebo group at 12 months. The resulting incremental cost-effectiveness ratio of £2,267 per QALY lost indicated that although costs were saved, health-related quality of life was lost. Even assuming symmetrical preferences regarding losses and gains for health benefits, the findings do not fall within the cost-effective region. Similar findings arose for analyses conducted from the societal perspective and using complete cases only. Conclusions: This economic evaluation indicates that hydroxychloroquine is unlikely to provide a cost-effective pain relief option for improving health-related quality of life in adult patients with moderate-to-severe hand osteoarthritis.