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Electric vehicles encounter significant challenges in colder climates due to reduced battery efficiency at low temperatures and increased electricity demand for cabin heating, which impacts vehicle propulsion. This study aims to address these challenges by implementing a thermal management system utilizing Phase Change Materials (PCMs) and validating the performance of a Multilayer Perceptron (MLP) model in predicting PCMs behavior and battery temperature distributions. The study employs an MLP model trained with 160 samples of diverse heat inputs, including pulsating, constant, wiener, discharging, and random temperatures. The model uses these temperatures as inputs and liquid fractions as target values. Performance evaluation is conducted using the MATLAB platform and is benchmarked against existing approaches, such as Long Short‐term Memory (LSTM), spatiotemporal convolutional neural network (CNN), and pooled CNN‐LSTM. The MLP model's accuracy in predicting PCMs phase transitions is validated by comparing predicted liquid fractions with numerically obtained values. Additionally, this study forecasts temperature distributions within a standard battery pack under various discharge scenarios, considering the performance of commercial lithium‐ion batteries. The proposed MLP model demonstrates high efficacy, achieving a correlation of up to 0.999 and root mean squared error below 0.013 compared with numerical results. [ABSTRACT FROM AUTHOR]

SUMMARY: Monoterpene synthases (MTSs) catalyze the first committed step in the biosynthesis of monoterpenoids, a class of specialized metabolites with particularly high chemical diversity in angiosperms. In addition to accomplishing a rate enhancement, these enzymes manage the formation and turnover of highly reactive carbocation intermediates formed from a prenyl diphosphate substrate. At each step along the reaction path, a cationic intermediate can be subject to cyclization, migration of a proton, hydride, or alkyl group, or quenching to terminate the sequence. However, enzymatic control of ligand folding, stabilization of specific intermediates, and defined quenching chemistry can maintain the specificity for forming a signature product. This review article will discuss our current understanding of how angiosperm MTSs control the reaction environment. Such knowledge allows inferences about the origin and regulation of chemical diversity, which is pertinent for appreciating the role of monoterpenoids in plant ecology but also for aiding commercial efforts that harness the accumulation of these specialized metabolites for the food, cosmetic, and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Aim: Patient‐reported outcome measures (PROMs) provide valuable information and promote shared decision‐making but are infrequently used in psychosis. Self‐rated Health (SRH) and Self‐rated Mental Health (SRMH) are single‐item PROMs in which respondents rate their health and mental health from 'poor' to 'excellent'. We examined the psychometric properties of the SRH and SRMH in early psychosis services in Chennai, India and Montreal, Canada. Methods: Assessments were completed in Tamil/English in Chennai and French/English in Montreal. Test–retest reliability included data from 59 patients in Chennai and Montreal. Criterion validity was examined against clinician‐rated measures of depression, anxiety, positive and negative symptoms, and a quality‐of‐life PROM for 261 patients in Chennai and Montreal. Results: SRH and SRMH had good to excellent test–retest reliability (ICC >0.63) at both sites and in English and Tamil (but not French). Results for criterion validity were mixed. In Montreal, low SRH was associated with not being in positive symptom remission, and poorer functioning and quality of life. SRH was associated only with functioning in Chennai. No associations were found for SRMH in Montreal. In Chennai, low SRMH was associated with not being in positive symptom remission and poorer functioning. Conclusions: Patient‐reported outcome measures may perform differently across contexts as a potential function of variations in sociodemographics, illness characteristics/course, understandings of health/mental health, and so forth. More work is needed to understand if discrepancies between PROMs and CROMs indicate poor validity of PROMs or 'valid' differences between patient and clinician perceptions. Our work suggests that single‐item PROMs can be feasibly integrated into clinical settings. [ABSTRACT FROM AUTHOR]

The reaction of substituted acylthiourea derivatives (L1–L4) with [(PPh3)2Cu(μ‐Cl)2Cu(PPh3)] in a proper stoichiometric proportion gave the complexes (1–4) in good yields. The structures of the compounds (ligands and complexes) were advocated through spectroscopic analyses and x‐ray diffraction (XRD) studies; the latter confirmed their molecular structures. The complexes (1–4) were assessed for their cytotoxic potential through MTT assay against A549, T24, and HepG2 cancer cells, and their toxicity was evaluated using Vero and MCF‐10a normal cells. The complexes (1–4) displayed better cytotoxic action toward HepG2 cancer cells than cisplatin. Complexes 3 and 4 significantly destroyed A549 cancer cells with the IC50 values of 16.25 and 4.90 μM, respectively, which were lower than that of cisplatin (IC50 = 17.73 μM). Furthermore, the higher IC50 values in normal cells showed that the complexes were less hazardous to the normal cells except complex 3. The biocompatibility study showed that the complexes had minimal impact on normal human dermal fibroblast (NHDF) cells. The mode of cell death of complexes 3 and 4 against cancer cells was evaluated using staining assays. Both compounds demonstrated a significant reduction in live cells, an increase in early apoptotic cells, and pronounced proapoptotic effects, as evidenced by fragmented nuclei. Flow cytometry revealed a distinctive subpopulation in the subG0 phase, highlighting the compounds' ability to induce apoptosis and inhibit cell cycle progression. [ABSTRACT FROM AUTHOR]

Background: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA‐mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes. Methods: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real‐time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool. Results: Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet‐specific, acinar cell‐specific and liver‐specific miRNAs were elevated at 6 h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre‐transplant levels 1‐year post‐transplant. Circulating miRNAs measured before and 6 h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post‐transplant. Conclusions: miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation. [ABSTRACT FROM AUTHOR]

The radical decline in climatic conditions coerces the world to take steps progressive toward implementing green energy technologies in all facets. The electric vehicle is one such huge leap toward providing a pollution‐free environment to the future generation, but the charging techniques in most cases utilize the power that is obtained using thermal power stations, and so on. This concludes it to be not completely green energy, therefore in this paper, considered two far‐reaching sources viz. photovoltaic and wind energy storage systems. The sources are also supported with the presence of an additional storage unit of battery energy storage system (BESS) and the overall system is managed by energy management system (EMS) that is designed using a simple state flow algorithm instead of complex machine learning methods. The electric vehicle (EV) is charged using wireless power transfer technology. The model is built using MATLAB—Simulink software and the simulation results are validated against the physical calculation carried out over the equivalent circuit model reduction method. The values were taken from the TATA Nexon EV for consideration and the output values are 400 V and 15 A to be provided for the charging of the EV at the receiving end of the wireless charging. [ABSTRACT FROM AUTHOR]

The research and development department continues searching for effective and definite anticancer medications that would help eradicate cancer. The thiosemicarbazone ligands with indole fragment were utilized to create four new copper(I) complexes. Several spectral examinations and elemental analyses validated the formation of the complexes (1–4). Single crystal X‐ray diffraction (XRD) also proved that complex 4 had the expected tetrahedral structure. Complexes 1–4 were assessed for their cytotoxic property on different cell lines such as immortalized human vascular endothelial (EAhy.926), hepatocellular carcinoma (HepG‐2), and bladder cancer (T24), and kidney epithelial normal cells extracted from an African green monkey (Vero). The complexes showed reduced toxicity towards healthy Vero cells while being active in cancer cell lines. While the standard cisplatin revealed IC50 values of 26.60 and 49.90 μM, the N‐phenyl substituted complex 3 displayed a superior cytotoxic effect with IC50 values of 13.82 and 24.93 μM towards EAhy.926 and HepG‐2 cells, respectively. [ABSTRACT FROM AUTHOR]

Aim: Despite their emphasis on engagement, there has been little research on patients' and families' experiences of care in early intervention services for psychosis. We sought to compare patients' and families' experiences of care in two similar early psychosis services in Montreal, Canada and Chennai, India. Because no patient‐ or family‐reported experience measures had been used in a low‐ and middle‐income context, we created a new measure, Show me you care. Here we present its development and psychometric properties. Methods: Show me you care was created based on the literature and stakeholder inputs. Its patient and family versions contain the same nine items (rated on a 7‐point scale) about various supportive behaviours of treatment providers towards patients and families. Patients (N = 293) and families (N = 237) completed the measure in French/English in Montreal and Tamil/English in Chennai. Test–retest reliability, internal consistency, convergent validity, and ease of use were evaluated. Results: Test–retest reliability (intra‐class correlation coefficients) ranged from excellent (0.95) to good (0.66) across the patient and family versions, in Montreal and Chennai, and in English, French, and Tamil. Internal consistency estimates (Cronbach's alphas) were excellent (≥0.87). The measure was reported to be easy to understand and complete. Conclusion: Show me you care fills a gap between principles and practice by making engagement and collaboration as central to measurement in early intervention as it is to its philosophy. Having been co‐designed and developed in three languages and tested in a low‐and‐middle‐income and a high‐income context, our tool has the potential for global application. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy (DMD) is a rare genetic disorder caused by decreased or absent dystrophin gene leading to progressive muscle degeneration and weakness in young boys. Disease progression models for the North Star Ambulatory Assessment (NSAA), a functional measurement widely used to assess outcomes in clinical trials, were developed using a longitudinal population modeling approach. The relationship between NSAA total score over time, loss of ambulation, and potential covariates that may influence disease progression were evaluated. Data included individual participant observations from an internal placebo‐controlled phase II clinical trial and from the external natural history database for male patients with DMD obtained through the Cooperative International Neuromuscular Research Group (CINRG). A modified indirect response model for NSAA joined to a loss of ambulation (LOA) time‐to‐event model described the data well. Age was used as the independent variable because ambulatory function is known to vary with age. The NSAA and LOA models were linked using the dissipation rate constant parameter from the NSAA model by including the parameter as a covariate on the hazard equation for LOA. No covariates were identified. The model was then used as a simulation tool to explore various clinical trial design scenarios. This model contributes to the quantitative understanding of disease progression in DMD and may guide model‐informed drug development decisions for ongoing and future DMD clinical trials. [ABSTRACT FROM AUTHOR]

Background: Nivolumab at a dose of 480 mg every 4 weeks (Q4W) is approved for the adjuvant treatment of melanoma. However, real‐world data on this regimen are limited in this setting. Methods: This retrospective observational study utilized data from the US Oncology Network iKnowMed electronic health record database and patient medical charts. Eligible patients were diagnosed with melanoma and received adjuvant nivolumab monotherapy from March to August 2018. Patients were grouped by dosing regimen: cohort 1 (C1), de novo nivolumab 480 mg Q4W; cohort 2 (C2), switched to nivolumab 480 mg Q4W after nivolumab 240 mg or 3 mg/kg every 2 weeks (Q2W); cohort 3 (C3), de novo nivolumab 3 mg/kg Q2W; or cohort 4 (C4), de novo nivolumab 240 mg Q2W. Patients were followed for up to 12 months. Duration of therapy and safety/tolerability were assessed. Results: One hundred ninety‐one patients were included (C1, n = 40; C2, n = 74; C3, n = 22; C4, n = 55). Duration of therapy was relatively consistent across cohorts (median, 10.3 months; range, 8.3–10.7). Likewise, proportions of patients experiencing treatment‐related adverse events (TRAEs) were similar (range, 54.5%–60.1%), as were the most common events (fatigue, rash, diarrhea, hypothyroidism, nausea, and pruritus). However, proportions experiencing 'significant' TRAEs varied between cohorts. Proportions discontinuing treatment were relatively consistent across cohorts. Propensity score matching and sensitivity analyses generally supported the unadjusted findings. Conclusions: Real‐world safety profiles of nivolumab 240 mg Q2W and 480 mg Q4W were similar, and both were comparable to the well‐documented safety of weight‐based dosing (3 mg/kg Q2W), further supporting their approval and use in the adjuvant setting for melanoma. [ABSTRACT FROM AUTHOR]

Aim: To compare social, recreational and independent functioning among persons with psychosis across two geo‐cultural contexts, we adapted the well‐established Social Functioning Scale (SFS) and translated it into French and Tamil. We present the development and psychometric testing of this adaptation, the SFS‐Early Intervention. Methods: Sixteen items were added to reflect contemporary youth activities (e.g., online games) and 31 items adapted to enhance applicability and/or include context‐specific examples (e.g., 'church activity' replaced with 'religious/spiritual activity'). Psychometric properties and participant feedback were evaluated. Results: Test–retest reliability (ICCs) ranged from 0.813 to 0.964. Internal consistency (Cronbach's α) ranged from.749 to.936 across sites and languages. Correlations with original subscales were high. The scale was rated easy to complete and understand. Conclusions: The SFS‐Early Intervention is a promising patient‐reported measure of social, recreational and independent functioning. Our approach shows that conceptually sound existing measures are adaptable to different times and contexts. [ABSTRACT FROM AUTHOR]

Denticity plays a prominent role in the cytotoxicity of metal complexes. The impact of ligand denticity of chromone/chromene thiosemicarbazones (TSCs) in the Ru(II)‐DMSO complexes on the cytotoxicity of cancer cells was evaluated. Ru(II)‐DMSO complex containing tridentate chromone TSC (D1) exhibited better in vitro anticancer activity than the one with bidentate chromene TSC (D2). Using the optimized structures of the complexes, the reason behind the same was attributed to the thermodynamically stable nature of the tridentate system. Hydrolysis study of the complexes showed the kinetically labile nature of the chloride ligand in the tridentate species with respect to the bidentate counterpart. The selective cytotoxicity of complex D1 against breast cancer cells and its less toxicity against normal cells demonstrated the effective anticancer potential of the complex. Further, the binding efficacy of the complexes against DNA and BSA, along with imaging and flow cytometry experiments, warranted the effective cell death induced by the complexes against breast cancer cells via apoptosis. [ABSTRACT FROM AUTHOR]

Introduction: The application of various lasers to treat periodontal and peri‐implant diseases is gaining momentum. While laser‐related dental research is ongoing, it is important to determine if current periodontal training programs are keeping pace with these new treatment modalities and actively incorporating them into their training. Materials and methods: An electronic survey was created to evaluate the extent to which lasers are currently being used in North American periodontal programs. A brief explanation of the study and a link to the 15‐question survey was emailed to 61 periodontal program directors requesting participation in the survey. The data regarding the prevalence of laser training in all the programs, which types of laser devices are used, and which surgical procedures are performed were collected and analyzed. Results: The response rate was 49.1% (n = 30). Among those responding to the survey, 76.7% (n = 23) of these programs reported providing clinical training in lasers, with the diode laser being the most frequently used (65.2%), followed by carbon dioxide (39.1%), neodymium‐doped yttrium aluminum garnet (26.1%), and erbium:yttrium aluminum garnet lasers (26.1%). Two major reasons for not utilizing lasers as part of regular patient care were cost and lack of evidence to support laser efficacy. Three out of seven programs that do not currently use lasers plan to provide laser training in the future. Over half (56.7%) of program directors did not think that lasers would become the standard of periodontal/implant care within the next 10 years, while 20% of them believed that they would. Conclusions: Laser training and education in postgraduate periodontal programs is still limited, and the majority of periodontal residents are not exposed to many types of laser devices. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether first‐episode psychosis patients receiving extended early intervention had better functional outcomes than those in regular care and to examine the predictors of functional outcomes. Methods: This is a randomized controlled single‐blind trial of 220 patients randomized after 2 years of early intervention to receive early intervention or regular care for the subsequent 3 years. Outcomes included cumulative time in functional recovery during the 3‐year trial assessed using the Social and Occupational Functioning Assessment Scale (SOFAS); and employment/education at last assessment which were, respectively, analyzed using multiple linear regression and logistic regression, accounting for well‐known predictors. Linear mixed and generalized linear models were also used to examine the course of SOFAS and employment/education over the 3‐year period. Results: The extended early intervention and regular care groups did not differ on time in functional recovery (mean = 50.17 weeks, SD = 46.62 vs. mean = 46.18 weeks, SD = 51.54); percent employed/in school (60.4% vs. 68.8%) or change in SOFAS or employment/education status over time. SOFAS scores were stable between years 2 and 5. Individuals with longer periods of total symptom remission experienced significantly longer periods of functional recovery and were likelier to be employed/in school. Those who had completed high school were nine times likelier to be employed/studying. Conclusion: Most individuals maintained functional gains accrued from 2 years of early intervention with no further improvement whether in extended early intervention or regular care. There was a gap between symptomatic and functional recovery, and one‐third were unemployed/not in school at year 5. The lack of additional progress even in extended early intervention suggests that specific interventions addressing functional roles need to be provided beyond the first 2 years of early intervention. Sustaining symptom remission and high‐school completion may be additional avenues for targeting functional recovery. [ABSTRACT FROM AUTHOR]

Aim: Nearly half of the patients with stillbirths experience reduced fetal movements (RFM) in the preceding week. The standardized evaluation will help reduce stillbirths. Placental dysfunction is the underlying pathophysiology for RFM and low cerebroplacental ratio (CPR). We attempted to determine the application of CPR in evaluation of RFM. Methods: A prospective case–control study with 100 patients each of cases and controls were studied at a tertiary care hospital. Middle cerebral artery pulsatility index (MCA‐PI), umbilical artery PI (UA‐PI), and CPR were calculated as multiples of median (MoM) in patients presenting with RFM after 30 weeks and their matched controls and followed up. CPR values of various gestation ranges and single versus multiple episodes of RFM were analyzed. Results: Compared to controls, women with RFM showed a significantly low MCA PI MoM (0.94 vs 1.4; p = 0.00008) and low CPR MoM (1.48 vs 1.6; p = 0.015). Women with multiple RFM episodes had lower CPR MoM (1.2 vs 1.5; p < 0.00001) compared to single episode RFM. Multiple RFM episode patients had low MCA PI MoM (1.3 vs 1.4; p = 0.0038) and low CPR MoM (1.2 vs 1.6; p < 0.00001) compared to controls. There was a significantly low CPR in 32–34 weeks (1.35 vs 1.81; p = 0.004) and 36–38 weeks subgroups (1.39 vs 1.58; p = 0.002). No significant difference in birthweight centiles or AGA versus SGA categories between cases and controls was noted questioning current guidelines where ultrasound evaluation is done for RFM patients with FGR. Conclusion: Incorporation of routine CPR measurements can standardize evaluation of RFM patients, especially those with AGA to pick up patients at risk of poor outcome and bring down stillbirth rates. [ABSTRACT FROM AUTHOR]

Objectives: There is growing policy impetus for including youth voices in health services research and health system reform. This article examines the perspectives of professionals in a mental healthcare organization charged with engaging young people as advisors in service transformation. Methods: An institutional ethnography of a youth mental health services organization in Ontario, Canada, was conducted. Fieldwork consisted of twelve months of observation of meetings, interviews with youth advisors and adult service providers, with subsequent text analysis of engagement training and policy materials. The present article reports data from six adult professionals and related field observations. Results: Service providers' efforts to engage youth were observed in three areas: a) supporting youth's development as advisors, b) retaining and deepening youth participation while waiting for organizational change and c) embedding relationships between youth and adults at various levels within the system of care. This work denotes existing tensions between the values and ideals of youth engagement and the everyday demands of services delivery. Conclusion: In this setting, a fundamental dimension of this work consisted of negotiating tensions between the policy enthusiasm for engagement and its realization in a health services context. In describing these contextual challenges, we outline implications for consideration by other youth mental health services. Engagement efforts that are authentic and sustained require resources and flexibility, and leadership commitment to instil service users' perspectives throughout multiple levels within the organization. [ABSTRACT FROM AUTHOR]

Cinnamon contains bioactive substances with diverse medicinal properties. We investigated the anticancer potential of abundant monophenols from cinnamon, namely, cinnamaldehyde, cinnamic acid, and eugenol, by hypothesizing that they possess proteasome inhibitory activities capable of suppressing cancer cell proliferation and inducing apoptosis. This hypothesis was tested by evaluating proteasome inhibitory activities of the compounds, and assessing downstream molecular and cellular events that are known to be impacted by proteasome inhibitors. The cinnamon compounds inhibited the catalytic activities of the proteasome in prostate cancer cells, but not in normal cells. Treatment with cinnamon compounds or the synthetic proteasome inhibitor MG132 upregulated p27 and IkBα proteins, and downregulated FoxM1 and angiogenic markers. These molecular events were associated with the decreased proliferation of prostate cancer cells. Treatment with cinnamon compounds or MG132 upregulated the expression of genes associated with endoplasmic reticulum (ER) stress/unfolded protein response (BIP, PERK, CHOP, and XBP1(S)). Furthermore, cinnamon compounds or MG132 upregulated the expression of genes required for the assembly of the caspase-8 activation platform in autophagosomes (LC3B, ATG5, p62, and Beclin1). The autophagy inhibitor, 3-methyladenine, blocked the compounds-mediated activation of caspase-8 and its downstream target caspase-3. In conclusion, proteasome inhibition by aromatic monophenols from cinnamon inhibits proliferation and leads to the death of prostate cancer cells by autophagy-dependent apoptosis. [ABSTRACT FROM AUTHOR]

Introduction: To study whether paternal age exerts an effect, independent of maternal age, on the outcomes of fresh in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Semen quality deteriorates with increasing paternal age; however, there is conflicting evidence for any impact paternal age may have on the outcome of IVF/ICSI. Several retrospective and prospective cohort studies have shown that paternal age increases the miscarriage rate and reduces the live birth rate. Some studies have shown no effect of paternal age on live birth rate or miscarriage rate. Studies involving donor oocytes have tended to show no independent effect of paternal age on assisted reproductive technology (ART) outcomes. The age at which paternal age may exert a significant deleterious effect on outcome is not known and there is no limit to paternal age in IVF/ICSI treatment. Material and methods: A single‐center retrospective cohort study was carried out at the Centre for Reproductive and Genetic Health, London, UK. Included in the analysis were all couples with primary or secondary infertility undergoing IVF/ICSI cycles in which the male partner produced a fresh semen sample and the cycle proceeded to fresh embryo transfer. All cycles of IVF/ICSI that used donor oocytes—donor sperm, frozen sperm, cycles leading to embryo storage and cycles including preimplantation genetic testing (PGT‐A/PGT‐M)—were excluded from analysis. The primary outcome was live birth rate and secondary outcomes were clinical pregnancy rate and miscarriage rate. Multivariate logistic regression analysis with live birth as a dependent variable and maternal and paternal age class as independent variables was performed. Results: During the study period there were 4833 cycles, involving 4271 men, eligible for analysis; 1974/4833 (40.8%, 95% confiene intervals [CI] 39.5–42.2%) cycles resulted in a live birth. A significantly lower proportion of men over 51 years met World Health Organization semen analysis criteria (56/133, [42.1%, 95% CI 34.1–50.6]) compared with men under 51 years of age (2530/4138 [61.1%, 95% CI 60.0–62.6]) (p = 0.001). Both maternal and paternal age were retained in the multivariate model and for all maternal age subgroups the probability of live birth decreased with paternal age over 50 years (odds ratio [OR] 0.674, 95% CI 0.482–0.943) (p = 0.021). Paternal age over 50 years was not an independent predictor of miscarriage (OR 0.678, 95% CI 0.369–1.250) (p = 0.214). Conclusions: Paternal age over 50 significantly affects the chance of achieving a live birth following ART. Paternal age does not independently affect the risk of miscarriage following ART. There should be a public health message for men not to delay fatherhood. [ABSTRACT FROM AUTHOR]

Aim: The issue of youth who are not engaged in education, employment or training has been a focus of policymakers for decades. Although interventions exist for these youth, they often measure success in ways that fail to capture what youth seek to gain. The project aims to address this gap by assessing youth‐oriented outcomes for interventions targeting upcoming youth. Acknowledging the stigma attached to the deficit‐based notion of not engaged in education, employment or training, hereafter we refer to 'upcoming youth', a term coined by youth partners on the project. This study asks what youth want to achieve by participating in an intervention for upcoming youth, with a view to guiding service and research design. Methods: A mixed‐methods discrete choice experiment will be conducted with youth engaged as partners. A qualitative (focus group) stage will be conducted to design discrete‐choice experiment attributes and levels. The experiment will be piloted and administered online to approx. 500 youth (aged 14‐29) across Canada to identify the outcomes that youth prioritize for interventions. Latent class analyses will then be conducted to explore clusters of outcomes that different groups of youth prioritize. Conclusions: From a strengths‐based recovery‐oriented framework, hearing the voices of the target population is important in designing and evaluating services. This youth‐oriented research project will identify the intervention outcomes that are the highest priority for upcoming youth. Findings will inform the development, implementation and testing of interventions targeting relevant outcomes for youth who are not engaged in education, employment or training. [ABSTRACT FROM AUTHOR]

Recombinant factor VIII Fc fusion protein (rFVIIIFc) has been indicated for adults and children with hemophilia A. The objective of this article was to build a population pharmacokinetic (PK) model using adult and pediatric data sets and explore relevant dosing scenarios across all ages. The activity‐time profiles of rFVIIIFc from 3 clinical studies (all trials registered at https://www.clinicaltrials.gov: NCT01027377, NCT01181128, and NCT01458106) were characterized, and covariates that determine variability of rFVIIIFc PK in children and adults were identified and implemented. Data sets were pooled to estimate population PK parameters. Simulations were conducted to generate activity‐time profiles at steady state (SS). The proportion of subjects maintaining SS trough >1 and >3 IU/dL and time >10 IU/dL were estimated. The rFVIIIFc model was a two‐compartment model that identified weight and von Willebrand factor as significant covariates. Model‐predicted SS peaks and troughs of rFVIIIFc activity‐time profiles confirmed the necessity of modifying dosing in pediatric subjects. The model also predicted that the average subject in the adult and adolescent group dosed with 40 IU/kg every 2 days maintained factor VIII activity >10 IU/dL for the entire duration. Children aged <6 years and aged 6 to <12 years receiving this dose maintained factor VIII activity of >10 IU/dL for nearly two‐thirds and three‐quarters of their time, respectively. In conclusion, these population PK analyses characterize activity‐time profiles for rFVIIIFc among pediatric and adult subjects. The model was used for simulation of clinically relevant dosing scenarios, which can provide better protection and better clinical outcomes. [ABSTRACT FROM AUTHOR]

In this Perspective Statement from The Obesity Society, the Clinical Committee discusses the use of weight loss supplements in the United States and the lack of regulatory oversight and rigorous testing of their efficacy and safety. A number of products and services claiming to promote weight loss are directly marketed to individuals with obesity and those wanting to lose weight. These products are not regulated as "drugs" by the Federal Drug Administration but, rather, are treated as dietary supplements if ingredients are "generally regarded as safe," requiring little or no testing to show efficacy or safety. Health care providers should be aware of the lack of evidence and deficiencies in regulatory oversight of dietary supplements marketed for weight loss. Regulatory authorities should protect consumers by ensuring accurate and safe marketing claims and preventing promotion of unproven and potentially unsafe products and claims. [ABSTRACT FROM AUTHOR]

Aim: We investigated whether individuals varied in their satisfaction with being randomized to an extension of early intervention (EI) for psychosis or regular care after 2 years of EI, and whether satisfaction was associated with service engagement 3 years later. Methods: Following randomization, patients (N = 220) indicated if they were happy with, unhappy or indifferent to their group assignment. Follow‐up with service providers was recorded monthly. Results: Patients randomized to extended EI were more likely to express satisfaction with their group assignment than those in the regular care group (88.2% vs 31.5%, χ2 = 49.96, P <.001). In the extended EI group, those happy with their assigned group were likelier to continue seeing their case manager for the entire five‐year period than those who were unhappy/indifferent (χ2 = 5.61, P =.030). Conclusions: Perceptions about EI, indicated by satisfaction with being assigned to extended EI, may have lasting effects on service engagement. [ABSTRACT FROM AUTHOR]

Background: India has a large youth population whose mental health needs must be addressed. This includes promotion of positive mental health, with early detection and effective intervention for mental health disorders. Understanding the perspectives of community stakeholders working with youth is pivotal to this effort. Current study aimed to bring together a group of community stakeholders (eg, parents, teachers, policy makers) to understand their perspectives on youth mental health problems, challenges in provision of care, and to provide recommendations to address these concerns at national level. Materials and methods: The study was conducted across two sites in India: Chennai and New Delhi. Three group meetings were conducted involving 52 participants, including governmental, non‐governmental and community representatives working with youth. The proceedings were manually recorded, transcribed, and analyzed using thematic analysis method. Results: Many youth mental health problems were similar across the two sites. The commonest drivers of mental health problems were reported to be academic pressure, substance use and problematic internet/social media use. Stigma and lack of awareness were identified as the most important challenges acting as barriers to seeking mental health help by youth. Prioritizing youth mental health as a national programmes along with strong political will were the major recommendations suggested by the stakeholders. Conclusion: Initial findings suggest that prioritizing youth mental health programmes in India would be advantageous. Inclusive and collaborative approach, involving community stakeholders working with youth in providing services that promote mental health and early access to care will help in developing healthy young citizens. [ABSTRACT FROM AUTHOR]

Fourteen new RuII–arene (p‐cymene/benzene) complexes (C1–C14) have been synthesized by varying the N‐terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure–activity relationships of the Ru–p‐cymene and Ru–benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR‐32 cancer cells, with C5 (Ru–p‐cymene complex containing C6H2(CH3)3 as N‐terminal substituent) and C13 (Ru–benzene complex containing C6H4(CF3) as N‐terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim‐1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells. [ABSTRACT FROM AUTHOR]

Over the last few decades, the advancement in reproductive technologies and protocols to improve embryo quality through culture techniques and genetic testing to eliminate chromosomally abnormal embryos resulted in better pregnancy rates and outcomes after fertility treatments. Unfortunately, some patients still struggle with recurrent implantation failures (RIFs) and recurrent pregnancy losses (RPLs). Immune etiologies have been attributed to play an important role in some of those patients. Maintaining a pre‐conceptional anti‐inflammatory environment for implantation and pregnancy continuation yields superior results. Intravenous immunoglobulin G (IVIG) treatment has been reported to enhance reproductive outcome in patients with RIF and RPL with immune dysregulations. In this systemic review, we analyzed outcomes of IVIG trials for RIF and RPL, its mechanism of action, dosing, administration, side‐effects, and evidence for its use in women with RIF and RPL. [ABSTRACT FROM AUTHOR]

This double‐blind, randomized, placebo‐controlled, dose‐ascending, first‐in‐human study (NCT02766621) assessed the safety, tolerability, and pharmacokinetics (PK) of PF‐06823859, an anti–interferon β monoclonal antibody. Healthy subjects were randomized to single ascending doses (SADs) of intravenous PF‐06823859 30, 100, 300, 900, or 2000 mg or placebo; to multiple ascending doses (MADs) of subcutaneous PF‐06823859 100 or 300 mg or placebo (once every 2 weeks for a total of 3 doses); or to MAD of intravenous PF‐06823859 600 mg or placebo (once every 3 weeks or once every 4 weeks for a total of 2 doses). The incidence, severity, and causal relationship of adverse events (AEs) were assessed, along with immunogenicity and PK. In total, 62 subjects were randomized to treatment (SAD, n = 35; MAD, n = 27). There were 76 treatment‐emergent all‐causality AEs in the SAD (PF‐06823859: n = 25; placebo: n = 4) and MAD (PF‐06823859: n = 40; placebo: n = 7) cohorts. In the SAD cohorts, all treatment‐emergent all‐causality AEs were mild in severity; 4 AEs of moderate severity were identified in the MAD cohorts. No dose‐limiting AEs, serious AEs, treatment‐related discontinuations, dose reductions, or deaths occurred. PF‐06823859 exposure increased dose‐proportionally, with half‐life values ranging between 23 and 35 days. The estimated subcutaneous bioavailability was 43% to 44%. Immunogenicity incidence rates were low (antidrug antibodies, 12.5%; neutralizing antibodies, 2.1%). No immunogenically related clinical responses of concern were observed. In conclusion, PF‐06823859 demonstrated an acceptable safety, tolerability, and PK profile that supports clinical development for treating disorders associated with increased interferon β levels, such as dermatomyositis or systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ageing is associated with an impaired cellular function that can affect tissue architecture and wound healing in gingival and periodontal tissues. However, the impact of oral fibroblast ageing on the structural organization of the extracellular matrix (ECM) proteins is poorly understood. Hence, in this study, we investigated the impact of cellular ageing of oral fibroblasts on the production and structural organization of collagen and other ECM proteins. Methods: Oral fibroblasts were serially subcultured, and replicative cellular senescence was assessed using population doubling time, Ki67 counts and expression of P21WAFI. The production and structural organization of ECM proteins were assessed at early (young‐oFB) and late (aged‐oFB) passages. The thickness and pattern of collagen produced by live cultures of young‐ and aged‐oFB were assessed using a label‐free and non‐invasive second harmonic generation (SHG)‐based multiphoton imaging. Expression of other ECM proteins (fibronectin, fibrillin, collagen‐IV and laminins) was evaluated using immunocytochemistry and confocal microscopy‐based depth profile analysis. Results: Aged‐oFB displayed a higher population doubling time, lower Ki67+ cells and higher expression of P21WAFI indicative of slower proliferation rate and senescence phenotype. SHG imaging demonstrated that young‐oFB produced a thick, interwoven network of collagen fibres, while the aged‐oFB produced thin and linearly organized collagen fibres. Similarly, analysis of immunostained cultures showed that young‐oFB produced a rich, interwoven mesh of fibronectin, fibrillin and collagen‐IV fibres. In contrast, the aged‐oFB produced linearly organized fibronectin, fibrillin and collagen‐IV fibres. Lastly, there was no observable difference in production and organization of laminins among the young‐ and aged‐oFB. Conclusion: Our results suggest that oral fibroblast ageing impairs ECM production and more importantly the organization of ECM fibres, which could potentially impair wound healing in the elderly. [ABSTRACT FROM AUTHOR]

Background: Engaging youth in research provides substantial benefits to research about youth‐related needs, concerns and interventions. However, researchers require training and capacity development to work in this manner. Methods: A capacity‐building intervention, INNOVATE Research, was co‐designed with youth and adult researchers and delivered to researchers in three major academic research institutions across Canada. Fifty‐seven attendees participated in this research project evaluating youth engagement practices, attitudes, perceived barriers, and perceived capacity development needs before attending the intervention and six months later. Results: The intervention attracted researchers across various career levels, roles and disciplines. Participants were highly satisfied with the workshop activities. Follow‐up assessments revealed significant increases in self‐efficacy six months after the workshop (P =.035). Among possible barriers to youth engagement, four barriers significantly declined at follow‐up. The barriers that decreased were largely related to practical knowledge about how to engage youth in research. Significantly more participants had integrated youth engagement into their teaching activities six months after the workshop compared to those who were doing so before the workshop (P =.007). A large proportion (71.9%) of participants expressed the need for a strengthened network of youth‐engaged researchers; other future capacity‐building approaches were also endorsed. Conclusions: The INNOVATE Research project provided improvements in youth engagement attitudes and practices among researchers, while lifting barriers. Future capacity‐building work should continue to enhance the capacity of researchers to engage youth in research. Researchers notably pointed to the need to establish a network of youth‐engaged researchers to provide ongoing, sustainable gains in youth engagement. [ABSTRACT FROM AUTHOR]

Aim: Frayme is a Canadian‐based international network designed to accelerate the adoption and scaling up of integrated youth services (IYS). This is done through the synthesis of evidence from a variety of sources and a commitment to integrated knowledge mobilization (KMb) to inform research policy and practice. Frayme is utilizing innovative approaches to stakeholder engagement (youth, families, policy makers, funders, researchers and practitioners) and KMb in order to co‐design system change. The purpose of this article describes the overall Frayme strategy and presents findings from a participatory needs assessment implemented to inform policy‐related priorities. Methods: The Frayme leadership team facilitated a participatory needs assessment with major stakeholder groups that applied a modified problem‐solving activity. The needs assessment was on a designed to support diverse stakeholder perspectives on ways to improve knowledge mobilization of IYS. Qualitative data were analysed using a thematic analysis. Results: The four themes identified through the needs assessment were: (a) traditional scientific practices, (b) organizational obstacles, (c) change aversion, and (d) pre‐established stakeholder hierarchies. Conclusions: Through the recognition of these challenges, Frayme has developed a set of major objectives to inform projects, opportunities for knowledge sharing, implementation of evidence and scaling up of efforts. The Frayme integrated KMb model represents a unique applied example of an evidence‐informed approach to practice collaboration in KMb to promote system change. The findings from this research also contribute to the expanding knowledge base with regard to complex evaluation and system transformation. [ABSTRACT FROM AUTHOR]

It is increasingly suggested that ecological and evolutionary sciences could inspire novel therapies against cancer but medical evidence of this remains scarce at the moment. The Achilles heel of conventional and targeted anticancer treatments is intrinsic or acquired resistance following Darwinian selection; that is, treatment toxicity places the surviving cells under intense evolutionary selective pressure to develop resistance. Here, we review a set of data that demonstrate that Darwinian principles derived from the "smoke detector" principle can instead drive the evolution of malignant cells toward a different trajectory. Specifically, long‐term exposure of cancer cells to a strong alarm signal, generated by the DNA repair inhibitor AsiDNA, induces a stable new state characterized by a down‐regulation of the targeted pathways and does not generate resistant clones. This property is due to the original mechanism of action of AsiDNA, which acts by overactivating a "false" signaling of DNA damage through DNA‐PK and PARP enzymes, and is not observed with classical DNA repair inhibitors such as the PARP inhibitors. Long‐term treatment with AsiDNA induces a new "alarm down" state in the tumor cells with decrease in NAD level and reactiveness to it. These results suggest that agonist drugs such as AsiDNA could promote a state‐dependent tumor cell evolution by lowering their ability to respond to high "danger" signal. This analysis provides a compelling argument that evolutionary ecology could help drug design development in overcoming fundamental limitation of novel therapies against cancer due to the modification of the targeted tumor cell population during treatment. [ABSTRACT FROM AUTHOR]

Background: There is increasing emphasis on engaging youth in research about youth, their needs, experiences and preferences, notably in health services research. By engaging youth as full partners, research becomes more feasible and relevant, and the validity and richness of findings are enhanced. Consequently, researchers need guidance in engaging youth effectively. This study examines the experiences, needs and knowledge gaps of researchers. Methods: Eighty‐four researchers interested in youth engagement training were recruited via snowball sampling. They completed a survey regarding their youth engagement experiences, attitudes, perceived barriers and capacity development needs. Data were analysed descriptively, and comparisons were made based on current engagement experience. Results: Participants across career stages and disciplines expressed an interest in increased capacity development for youth engagement. They had positive attitudes about the importance and value of youth engagement, but found it to be complex. Participants reported requiring practical guidance to develop their youth engagement practices and interest in a network of youth‐engaged researchers and on‐going training. Those currently engaging youth were more likely to report the need for greater appreciation of youth engagement by funders and institutions. Conclusions: Engaging youth in research has substantial benefits. However, skills in collaborating with youth to design, conduct and implement research have to be learned. Researchers need concrete training and networking opportunities to develop and maximize these skills. They also need mechanisms that formally acknowledge the value of engagement. Researchers and those promoting youth engagement in research are encouraged to consider these findings in their promotion and training endeavours. [ABSTRACT FROM AUTHOR]

Background: The combined use of interleukin‐1β and tumor necrosis factor–α blockers in the peritransplant period has improved outcomes of total pancreatectomy with islet autotransplantation (TPIAT). However, these drugs may suppress the immune system, resulting in severe infection. Methods: We retrospectively investigated the impact of microbial‐contaminated islet product on posttransplant complications and metabolic outcomes of TPIAT patients receiving the IL‐1β and TNF‐blockade treatment at our center. Results: Among 108 TPIAT patients, 37 patients (34%) received contaminated products. Preoperative stent treatment and fibrosis score were independent risk factors for the contamination. There were no significant differences between the contaminated and noncontaminated product groups in posttransplant infectious complication rate, length of hospitalization, or readmission rate. However, islet equivalents (P <.0001) and insulin independence rate (P =.036) at 6 months were significantly lower for patients receiving contaminated product. Conclusions: These results suggest that combined anti‐inflammatory drug use is safe and well tolerated in TPIAT patients who receive contaminated islet product and does not increase the rate of infectious complications; however, contaminated islet product is associated with poor metabolic outcomes. [ABSTRACT FROM AUTHOR]

Aim: Over the past two decades, the youth mental health field has expanded and advanced considerably. Yet, mental disorders continue to disproportionately affect adolescents and young adults. Their prevalence and associated morbidity and mortality in young people have not substantially reduced, with high levels of unmet need and poor access to evidence‐based treatments even in high‐income countries. Despite the potential return on investment, youth mental disorders receive insufficient funding. Motivated by these continual disparities, we propose a strategic agenda for youth mental health research. Method: Youth mental health experts and funders convened to develop youth mental health research priorities, via thematic roundtable discussions, that address critical evidence‐based gaps. Results: Twenty‐one global youth mental health research priorities were developed, including population health, neuroscience, clinical staging, novel interventions, technology, socio‐cultural factors, service delivery, translation and implementation. Conclusions: These priorities will focus attention on, and provide a basis for, a systematic and collaborative strategy to globally improve youth mental health outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Intracytoplasmic morphologically selected sperm injection (IMSI) is one of the sperm selection techniques used for assisted reproduction which has been applied for a variety of indications including previously failed fertilization with intracytoplasmic sperm injection (ICSI). A Cochrane review1 found no difference in outcomes between either modality of sperm selection. Since the Cochrane review was published there have been a further two randomized controlled trials comparing IMSI and ICSI. This systematic review and meta-analysis aims to compare IMSI with ICSI as insemination methods regarding live birth rate and miscarriage rate.Material and Methods: Systematic review of randomized controlled trials, observational studies and similar reviews in electronic databases published before January 2018.Results: We found nine randomized controlled trials, evaluating 1610 cycles of in vitro fertilization and 15 observational studies evaluating 1243 cycles of in vitro fertilization. Meta-analysis of the included randomized controlled trials showed no difference in the live birth rate or miscarriage rate between the ICSI and IMSI groups. Meta-analysis of five observational studies showed a significantly higher number of live births in the IMSI group than ICSI group (live birth rate odds ratio 1.47, 95% confidence interval 1.16-4.07), with a moderate degree of heterogeneity (I2  = 41%). Additionally, from six observational studies, a significantly lower miscarriage rate was observed in the IMSI group than in the ICSI group (odds ratio 0.51, 95% confidence interval 0.37-0.70, I2  = 0%).Conclusions: Meta-analysis of randomized studies comparing IMSI to ICSI has not shown any difference in live birth rate and miscarriage rate. Meta-analysis of observational studies, which must be interpreted with caution, revealed an increased live birth rate and decreased miscarriage rate with IMSI vs ICSI. [ABSTRACT FROM AUTHOR]

Eliciting a weight history can provide clinically important information to aid in treatment decision-making. This view is consistent with the life course perspective of obesity and the aim of patient-centered care, one of six domains of health care quality. However, thus far, the value and practicality of including a weight history in the clinical assessment and treatment of patients with obesity have not been systematically explored. For these reasons, the Clinical Committee of The Obesity Society established a task force to review and assess the available evidence to address five key questions. It is concluded that weight history is an essential component of the medical history for patients presenting with overweight or obesity, and there are strong and emerging data that demonstrate the importance of life stage, duration of exposure to obesity, maximum BMI, and group-based trajectory modeling in predicting risk for increased morbidity and mortality. Consideration of these and other patient-specific factors may improve risk stratification and clinical decision-making for screening, counseling, and management. Recommendations are provided for the key elements that should be included in a weight history, and several needs for future clinical research are outlined. [ABSTRACT FROM AUTHOR]

Opsin‐based transmembrane voltage sensors (OTVSs) are increasingly important tools for neuroscience enabling neural function in complex brain circuits to be explored in live, behaving animals. However, the visible wavelengths required for fluorescence excitation of the current generation of OTVSs limit optogenetic imaging in the brain to depths of only a few mm due to the strong absorption and scattering of visible light by biological tissues. We report that substitution of the native A1 retinal chromophore of the widely used QuasAr1/2 OTVSs with the retinal analog MMAR containing a methylamino‐modified dimethylphenyl ring results in over a 100‐nm redshift of the maxima of the absorption and fluorescence emission bands to near 700 and 840 nm, respectively. FT‐Raman spectroscopy reveals that at pH 7 QuasAr1 with both the A1 and MMAR chromophores possess predominantly an all‐trans protonated Schiff base configuration with the MMAR chromophore exhibiting increased torsion of the polyene single‐/double‐bond system similar to the O‐intermediate of the BR photocycle. In contrast, the A1 and the MMAR chromophores of QuasAr2 exist partially in a 13‐cis PSB configuration. These results demonstrate that QuasArs containing the MMAR chromophore are attractive candidates for use as NIR‐OTVSs, especially for applications such as deep brain imaging. [ABSTRACT FROM AUTHOR]

Aim: This paper aims to examine how existing mental health within the city of Chennai, India manages first‐episode psychosis, to determine lacunae and barriers in providing effective early intervention and to make appropriate recommendations to improve the care of first‐episode psychosis patients. Methods: Interviews were held with 15 health professionals to capture information on current practices and facilities available for the management of first‐episode psychosis. Results: No specialized clinic or services were available for individuals with first‐episode psychosis in Chennai, except one. Pharmacotherapy was the main treatment modality with psychological support to patients and families. Most common drugs used were Risperidone, Olanzapine, and Haloperidol in their recommended doses. General practitioners and paediatricians, due to inadequate training in mental health, referred patients with psychosis to mental health professionals. Conclusions: Equipping the existing mental health services to manage FEP and training all health professionals on psychosis will improve FEP management in Chennai. [ABSTRACT FROM AUTHOR]

Low‐potency corticosteroid betamethasone valerate and vitamin‐A tazarotene are used in combination for effective treatment of psoriasis. There is no robust high‐performance liquid chromatography analytical technique available for simultaneous estimation of betamethasone valerate and tazarotene in conventional and nanocarriers based formulations. A simple, accurate, robust isocratic high‐performance liquid chromatography method was developed for simultaneous estimation of betamethasone valerate and tazarotene in topical pharmaceutical formulations. The developed method was validated as per the regulatory guidelines. The validated method was linear over the concentration range of 150–6000 ng/mL (r2 > 0.999) at 239 nm wavelength. Limits of detection and quantification of two analytes were 50 and 150 ng/mL, respectively. The %relative standard deviation for intraday and interday precision was less than 2%. The method was also evaluated in the presence of forced degradation conditions. The developed method was successfully applied for in vitro and ex vivo drug release studies of in‐house designed nanoformulations. [ABSTRACT FROM AUTHOR]

Aims: To explore the impact of a targeted case identification intervention, with training and education regarding first‐episode psychosis and clinical high‐risk syndromes, on the referral and identification of those at high risk. Methods: Using a historical control design, referral information from pre‐intervention and post‐intervention periods was collected via administrative data and clinician notes from a catchment‐based early psychosis service. Results: A significant increase in the number of referrals sent to the service's clinical high‐risk unit was observed following the intervention (P = 0.01). The proportion of referrals eligible was significantly higher post‐intervention (P = 0.03), with the majority (26/44, 59.1%) referred via the first‐episode psychosis service unit. Conclusions: An integrated outreach intervention for both first‐episode psychosis and the clinical high‐risk state was effective in increasing referrals of eligible cases to the service's at‐risk unit. Rather than being stage‐specific, targeted case identification strategies and service integration should span across the early stages of psychosis. [ABSTRACT FROM AUTHOR]

Archaerhodopsin‐3 (AR3) is a member of the microbial rhodopsin family of hepta‐helical transmembrane proteins, containing a covalently bound molecule of all‐trans retinal as a chromophore. It displays an absorbance band in the visible region of the solar spectrum (λmax 556 nm) and functions as a light‐driven proton pump in the archaeon Halorubrum sodomense. AR3 and its mutants are widely used in neuroscience as optogenetic neural silencers and in particular as fluorescent indicators of transmembrane potential. In this study, we investigated the effect of analogs of the native ligand all‐trans retinal A1 on the spectral properties and proton‐pumping activity of AR3 and its single mutant AR3 (F229S). While, surprisingly, the 3‐methoxyretinal A2 analog did not redshift the absorbance maximum of AR3, the analogs retinal A2 and 3‐methylamino‐16‐nor‐1,2,3,4‐didehydroretinal (MMAR) did generate active redshifted AR3 pigments. The MMAR analog pigments could even be activated by near‐infrared light. Furthermore, the MMAR pigments showed strongly enhanced fluorescence with an emission band in the near‐infrared peaking around 815 nm. We anticipate that the AR3 pigments generated in this study have widespread potential for near‐infrared exploitation as fluorescent voltage‐gated sensors in optogenetics and artificial leafs and as proton pumps in bioenergy‐based applications. [ABSTRACT FROM AUTHOR]

Aim: Youth mental health is of paramount significance to society globally. Given early onset of mental disorders and the inadequate access to appropriate services, a meaningful service transformation, based on globally recognized principles, is necessary. The aim of this paper is to describe a national Canadian project designed to achieve transformation of mental health services and to evaluate the impact of such transformation on individual and system related outcomes. Method: We describe a model for transformation of services for youth with mental health and substance abuse problems across 14 geographically, linguistically and culturally diverse sites, including large and small urban, rural, First Nations and Inuit communities as well as homeless youth and a post‐secondary educational setting. The principles guiding service transformation and objectives are identical across all sites but the method to achieve them varies depending on prevailing resources, culture, geography and the population to be served and how each community can best utilize the extra resources for transformation. Results: Each site is engaged in community mapping of services followed by training, active stakeholder engagement with youth and families, early case identification initiatives, providing rapid access (within 72 hours) to an assessment of the presenting problems, facilitating connection to an appropriate service within 30 days (if required) with no transition based on age within the 11 to 25 age group and a structured evaluation to track outcomes over the period of the study. Conclusions: Service transformation that is likely to achieve substantial change involves very detailed and carefully orchestrated processes guided by a set of values, principles, clear objectives, training and evaluation. The evidence gathered from this project can form the basis for scaling up youth mental health services in Canada across a variety of environments. [ABSTRACT FROM AUTHOR]

Aim: This study describes how mental health services for youth are being transformed within the context of a semi‐urban and rural region of Canada (Chatham‐Kent, Ontario), based on the framework of ACCESS Open Minds (ACCESS OM), a pan‐Canadian youth mental health research and evaluation network. Methods: Transformation has focused on the five key objectives of ACCESS OM, namely early identification, rapid access, appropriate care, continuity of care, and youth and family engagement. A community mapping process was conducted at the beginning of the transformation to help develop a comprehensive inventory of services, identify challenges and optimize partnerships to address the five key objectives. Results: The following strategies represent key elements in the transformation: coordination and partnerships between hospital, community and voluntary organizations, as well as different sectors of the community (e.g., Child and Youth Services, Education, Community Safety and Correctional Services, CSCS); working with local champions (e.g., Youth Diversion Officer and the Mental Health and Addictions Nurse in the school sectors); establishing a youth‐friendly space in a central part of the community, where services are co‐located and operate within an open‐concept design; training of ACCESS Clinicians to conduct an initial assessment; engaging youth and family in service‐level recruitment, planning, daily operations, and evaluation, including hiring of youth and family peer navigators; and, engaging the community through awareness and educational events. Conclusions: The success of this transformation needs to be measured on various outcome parameters, but it is notable that neighbouring communities are already beginning to implement a similar model. [ABSTRACT FROM AUTHOR]

Aim: Demands for mental health services in post‐secondary institutions are increasing. This paper describes key features of a response to these needs: ACCESS Open Minds University of Alberta (ACCESS OM UA) is focused on improving mental health services for first‐year students, as youth transition to university and adulthood. Methods: The core transformation activities at ACCESS OM UA are described, including early case identification, rapid access, appropriate and timely connections to follow‐up care and engagement of students and families/carers. In addition, we depict local experiences of transforming existing services around these objectives. Results: The ACCESS OM UA Network has brought together staff with diverse backgrounds in order to address the unique needs of students. Together with the addition of ACCESS Clinicians these elements represent a systematic effort to support not just mental health, but the student as a whole. Key learnings include the importance of community mapping to developing networks and partnerships, and engaging stakeholders from design through to implementation for transformation to be sustainable. Conclusions: Service transformation grounded in principles of community‐based research allows for incorporation of local knowledge, expertise and opportunities. This approach requires ample time to consult, develop rapport between staff and stakeholders across diverse units and develop processes in keeping with local opportunities and constraints. Ongoing efforts will continue to monitor changing student needs and to evaluate and adapt the transformations outlined in this paper to reflect those needs. [ABSTRACT FROM AUTHOR]

Aim: ACCESS Open Minds (ACCESS OM) is a pan‐Canadian project aimed at improving youth mental healthcare. This paper describes implementation of the ACCESS OM objectives for youth mental health service transformation within a pre‐existing Fish Net Model of transformative youth mental healthcare service in the First Nation community of Eskasoni, on Canada's east coast. Methods: We describe an adaptation of the ACCESS OM service transformation objectives through the complementary blending of Indigenous and Western methodologies. This concept of "Two‐Eyed Seeing" is illustrated as central to engaging youth in the community and attending to their mental health needs and wellness. Results: The ACCESS OM Eskasoni First Nation Youth Space acts as a central location for the site team and its activities, which expand into the rest of the community to facilitate early identification of youth in need. Rapid access to care is promoted via barrier‐free availability through a central intake crisis and referral centre, and ease of contact through social media and other modalities. Youth are given the choice between standard Western mental health services, or Indigenous methods of improving well‐being, or a combination of the two. Conclusions: The ACCESS OM framework has shown early results of being a positive addition to the Eskasoni community. Local leadership and community buy‐in are identified as key factors to success. Further exploration, research, and evaluation of this transformation is ongoing. Successful implementation of this model in Eskasoni could act as a model for youth mental health programmes in other First Nations across Canada. [ABSTRACT FROM AUTHOR]

Aim: To describe a community‐specific and culturally coherent approach to youth mental health services in a small and remote northern Indigenous community in Canada's Northwest Territories, under the framework of ACCESS Open Minds (ACCESS OM), a pan‐Canadian youth mental health research and evaluation network. Methods: As 1 of the 14 Canadian communities participating in a 5‐year, federally funded service transformation and evaluation project, the arctic Inuit community of Ulukhaktok has undertaken culturally relevant adjustments in their delivery of youth mental wellness services and related community wellness initiatives. These enhancement activities highlight connections to culture and traditional skills, honour youth‐ and community‐expressed desires to incorporate Inuvialuit‐specific approaches to wellness, and strengthen the support systems to improve access to mainstream mental healthcare, when needed. The adaptation of a Lay Health Worker model from Global Mental Health to the local circumstances resulting in creation of lay community health workers is central to this approach in meeting contextual needs. Results: Community leaders identified key activities for sustainable change, including human capital development, authentic collaboration and diversified engagement strategies. Building around five ACCESS OM objectives, the local site team in Ulukhaktok has identified its youth programming and mental wellness service gaps through an ongoing process of community mapping. Conclusions: Information from service providers, youth and other community members demonstrates attuning of the ACCESS OM framework to Inuit paradigms in Ulukhaktok. It could prove to be a sustainable prototype for delivering youth mental health services in other communities in the Inuvialuit Settlement Region and possibly across the entire Inuit Nunangat. It needs, however, to be further supported by easier access to specialized mental health services when needed. [ABSTRACT FROM AUTHOR]

Aim: This paper describes how the transformation of youth mental health services in the rural Francophone region of the Acadian Peninsula in New Brunswick, Canada, is meeting the five objectives of ACCESS Open Minds. Methods: Implementation of the ACCESS Open Minds framework of care in the Acadian Peninsula of New Brunswick began in 2016 at a well‐established volunteer centre and community‐based mental health organization. Through focus groups with youth aged 14 to 22 (n = 13), community mapping was used to describe the youth‐related mental health service transformation, followed by thematic analysis, validation by member checking and triangulation. Results: Preliminary results show a generally successful implementation of the ACCESS Open Minds model, as evidenced by the transformation of mental health service provision, the enhancement of capacity in human resources and the participation of youth. Transformation was evidenced across the five objectives of mental healthcare of ACCESS Open Minds, albeit to variable extents. Several facilitating factors and challenges are identified based on youths' accounts. Conclusions: It is possible to successfully implement the ACCESS Open Minds model among francophones living in a minority setting and despite the constraints of a rural area. Most key components of the framework were implemented with high program fidelity. The rural context presents unique challenges that require creative and effective use of resources, while offering opportunities that arise from a culture of resourcefulness and collaboration. [ABSTRACT FROM AUTHOR]

Aim: In many parts of the world, there is growing concern about youth homelessness. Homeless youth are particularly vulnerable to psychological distress, substance use and mental disorders, and premature mortality caused by suicide and drug overdose. However, their access to and use of mental health care is very limited. Methods: The Réseau d'intervention de proximité auprès des jeunes (RIPAJ), a Montreal network of over 20 community stakeholders providing a wide array of cohesive services, was created to ease homeless youth's access to mental health and psychosocial services. Its philosophy is that there should be no "wrong door" or "wrong timing" for youth seeking help. In 2014, the network partnered with the pan‐Canadian transformational research initiative, ACCESS Esprits ouverts. Results: Created through this partnership, ACCESS Esprits ouverts RIPAJ has been promoting early identification through outreach activities targeting homeless youth and agencies that serve them. An ACCESS Clinician was hired to promote and rapidly respond to help‐seeking and referrals. By strengthening connections within RIPAJ and using system navigation, the site is working to facilitate youth's access to timely appropriate care and eliminate age‐based transitions between services. A notable feature of our program, that is not usually evident in homelessness services, has been the engagement of the youth in service planning and design and the encouragement of contact with families and/or friends. Conclusion: Challenges remain including eliminating any remaining age‐related transitions of care between adolescent and adult services; and the sustainability of services transformation and network coordination. Nonetheless, this program serves as an example of an innovative, much‐needed, community‐oriented model for improving access to mental health care for homeless youth. [ABSTRACT FROM AUTHOR]

Aim: This paper outlines the transformation of youth mental health services in Edmonton, Alberta, a large city in Western Canada. We describe the processes and challenges involved in restructuring how services and care are delivered to youth (11‐25 years old) with mental health needs based on the objectives of the pan‐Canadian ACCESS Open Minds network. Methods: We provide a narrative review of how youth mental health services have developed since our engagement with the ACCESS Open Minds initiative, based on its five central objectives of early identification, rapid access, appropriate care, continuity of care, and youth and family engagement. Results: Building on an initial community mapping exercise, a service network has been developed; teams that were previously age‐oriented have been integrated together to seamlessly cover the age 11 to 25 range; early identification has thus far focused on high‐school populations; and an actual drop‐in space facilitates rapid access and linkages to appropriate care within the 30‐day benchmark. Conclusions: Initial aspects of the transformation have relied on restructuring and partnerships that have generated early successes. However, further transformation over the longer term will depend on data demonstrating how this has impacted clinical outcomes and service utilization. Ultimately, sustainability in a large urban centre will likely involve scaling up to a network of similar services to cover the entire population of the city. [ABSTRACT FROM AUTHOR]

Dental students often underestimate their probing depth (PD) measurements, which emphasizes the need for effective and novel methods for teaching proper probing technique. The aim of this study was to evaluate the efficacy of audiovisual learning aids, recorded from the point of view of examiners, for improvement in PD agreement in dental students. In 2017‐18, 22 third‐year dental students were randomized into test and control groups. Each student and a single blinded faculty examiner performed PD measurements on a minimum of three patients. The test group viewed a video demonstrating proper probing technique, while the control group received only probing technique instruction from prior lectures. All measurements, the periodontal diagnoses, and the total time taken to complete PD measurements were recorded. A survey of student attitudes about the audiovisual tool was conducted after the intervention; all 22 students completed the survey. A total of 11,426 PD sites were measured. The test group had 10% greater accuracy in PD sites=4 mm. The control group had a minor but statistically significant increase in accuracy for 2 mm PD sites. For all incorrect measurements at sites PD≥4, the students tended to underestimate the PD. Tooth type, site location around tooth, and diagnosis had no significant effect on PD measurement agreement. No significant difference between groups was found for the proportions of gingivitis and periodontitis patients or for examination time. This study found that use of the audiovisual learning aid "Calibrated Periodontal Training Video" improved the students' probing depth accuracy for sites with PD of 4 mm. [ABSTRACT FROM AUTHOR]