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Background & Aims: Anatomical variations in the branching pattern of arch of aorta are significant for diagnostic, surgical, and interventional procedures of the thorax and neck, and failure to recognize these patterns may have fatal outcome. Hence the present study aims to determine the percentage and type of aortic arch variations. Materials & Methods: This cross-sectional study was conducted on 30 formalin-fixed stillborn human fetuses of 35 weeks gestational age and above, in the Department of Anatomy, RIMS, Imphal, Manipur from 2018 to 2020. stillborn human fetuses were collected from the Obstetrics and Gynecology Department of RIMS, Imphal, Manipur, after taking due consent from parent. Fetus with gross abnormality and weighing less than 2.5 kg were excluded. whereas above 2.5 kg weight fetuses were included. The variations in the branching pattern of aortic arch were observed, noted and photographed. The variations were according to the classification by vicurevic et al., 2012. Results: The classical pattern of three branches of the arch of aorta were seen in 23 (76.66%) cases in the present study. In the remaining 7 (23.33%) cases, two different types of variations were observed with four and two branches arising in five and two cases respectively. Conclusion: Knowledge of normal anatomy and frequency in the variations in the branching pattern of the arch of aorta in the present study can be of significance for clinicians.

Caffeic acid, a potent polyphenol belonging to the hydroxycinnamic acid derivative class, was utilized in the synthesis of silver nanoparticles (AgNPs) at ambient temperature. The resultant conjugates underwent comprehensive characterization employing various analytical techniques, including UV–visible spectroscopy, FTIR, RAMAN spectroscopy, dynamic light scattering (DLS) for size and zeta potential analysis, atomic force microscopy (AFM), and scanning electron microscopy (SEM). Through these analyses, the morphological characteristics of the synthesized nanoparticles were elucidated, providing valuable insights into their structural properties. Subsequently, the cytotoxic effects of the caffeic acid-synthesized silver nanoparticles were assessed against A549 cells over a 48-h period by MTT assay. Remarkably, these nanoparticles exhibited significant toxicity towards the cells, with inhibitory effects observed at concentrations of 141 μg/ml for CA AgNPs. This underscores their potential as potent agents against cancer cells. Furthermore, the profound significance of caffeic acid-synthesized silver nanoparticles was evaluated specifically against A549 lung cancer cells. This was corroborated through cell cycle analysis, which demonstrated the potent anticancer activity of the caffeic acid-synthesized silver nanoparticles. Such findings suggest promising prospects for their utilization in diverse cancer treatment modalities. Overall, the successful synthesis and characterization of caffeic acid-synthesized silver nanoparticles underscore their potential as potent agents against cancer, particularly in combating A549 lung cancer cells. Further research and exploration into their mechanisms of action and potential synergistic effects with existing anticancer therapies could unveil additional avenues for their clinical translation and utilization in cancer management.

Aggregate wick system (AWS) or capillary action technique is a kind of sub-surface irrigation system gaining popularity owing to its profound advantages of improved water and nutrient use efficiency resulting in superior plant growth and development. However, its effect on growth and physiology of gerbera crop has not been studied yet. Therefore, an experiment was conducted during 2021–23 at ICAR-Indian Institute of Horticultural Research, Bengaluru, Karnataka to assess the effect of aggregate wick system on growth, flowering, vase life, yield and physiological aspects of gerbera var. Arka Nesara as compared to the conventional drip systems. It was apparent from the results that higher overall factor productivity in terms of number of leaves/plant (12.92), earlier first flower harvest (149.80 days) and copious flower production (38.58/plant/year) with enhanced chlorophyll content and optimal starch content were observed with AWS on the soil bed. However, AWS with pots on the ground resulted in extended vase life (9.20 days) with enhanced leaf area (115.31 cm2), chlorophyll-b, reducing sugars and decreased total and non-reducing sugars in leaves. Therefore, it can be concluded that the improved flower yield and vase life of gerbera in aggregate wick systems might be attributed to the greater chlorophyll production and reducing sugars in the leaves, respectively.

Summary: This Viewpoint presents an overview of trials methodology research (TMR) and the case for investing in TMR in India. Randomised controlled trials and other types of clinical research inform evidence-based medicine, but this endeavour is dependent on the quality of such research. TMR is aimed at improving the way in which clinical trials are designed, conducted, analysed, and reported. The evolution of TMR in countries like the UK has been nurtured through dedicated funding support. Similar funding opportunities for TMR in India will help optimise the ethical and methodological rigour of the growing number of trials conducted in India. Such funding could help initiate an interdisciplinary network of key stakeholders in India to lead on TMR priority-setting exercises so that methodological questions of relevance to India are addressed. The establishment of trials methodology hubs will enhance initiatives such as the disease-specific clinical trials networks being set up as part of the National Biopharma Mission in India. We posit that promoting and establishing TMR as a distinct field of study in India will ensure the improvement of our health research ecosystem and call on national and international funding bodies to initiate consultation, consensus building and ringfenced funding for TMR in India.

Abstract Background In addition to the conventional aetiologic agents of oropharyngeal squamous cell carcinoma (OPSCC) such as tobacco usage, alcohol consumption and betel quid usage, it has been established that a proportion of OPSCC are driven by persistent oncogenic human papillomavirus (HPV) infections. Currently, there is a lack of data on the burden of HPV- associated OPSCC in Asian countries including Malaysia. Methods A cross-sectional multicentre study with tissue analysis of Malaysian patients diagnosed with primary OPSCC within a five-year period, from 2015 to 2019 between 01/01/2015 to 31/12/2019 was undertaken. Determination of HPV status was carried out using p16INK4a immunohistochemistry on tissue microarrays constructed from archived formalin-fixed paraffin-embedded tissue. Results From the cases identified, 184 cases had sufficient tissue material for analysis. Overall, median age at diagnosis was 63.0 years (IQR = 15) and 76.1% of patients were males. In our cohort, 35.3% of patients were Indian, 34.2% were Chinese, 21.2% were Malay and 9.2% were from other ethnicities. The estimated prevalence of HPV-associated OPSCC in our cohort was 31.0% (CI 24.4–38.2%). The median age for the HPV-associated OPSCC sub-group of patients was not significantly lower than the median age of patients with HPV-independent OPSCC. More than half of HPV-associated OPSCC was seen in patients of Chinese ethnicity (54.4%). Patients with HPV-associated OPSCC had a much better overall survival than patients with HPV-independent OPSCC (Log rank test; p

Abstract Hydrothermal carbonization (HTC) is a promising technology for waste valorisation and nutrient recovery to achieve sustainability. HTC converts organic waste into hydrochar, a carbon‐rich solid with numerous surface functionalities that can be used for energy and wastewater treatment. In this review, we highlight the potential of hydrochar‐based technology for improving the performance of anaerobic digestion (AD) systems and downstream applications of nutrient‐laden hydrochar. We identify knowledge gaps in hydrochar production, performance in AD systems and nutrient recovery, including the need for larger‐scale production facilities, multielement adsorption studies, and computational modelling. Techno‐economic analysis and life cycle assessment of hydrochar applications are critical to evaluating the commercial viability of this technology. Overall, hydrochar‐based technology offers a sustainable solution for waste management and resource recovery, with potential socioeconomic benefits for developing economies. The deployment of hydrochar‐based technology will directly address key issues highlighted in the United Nations' Sustainable Development Goals such as Clean water and sanitation (SDG 6); Zero hunger (SDG 2); and Climate action (SDG 13) thereby contributing to a more sustainable future.

Seashell is a hard, protective outer layer created by an animal that lives in the sea. Empty seashells are often found washed up on beaches by beachcombers. This marine by-product can be used to partial replacement of coarse aggregate or cement in concrete. This paper describes the use of seashell powder and aggregate in the concrete for the replacement of cement and coarse aggregate. The effect of seashell waste in the concrete was studied in terms of its compressive strength, tensile strength and flexural strength after 28, 56 and 90 days of curing. The replacement of cement by seashell powder were 10%, 20% and 30% and replacement of coarse aggregate by seashell aggregate are 5%, 10% and 15%. The properties of seashell concrete were compared with control mix specimen of M25 grade of concrete. Also, it has been tried to predict the strength of the seashell concrete utilizing adaptive neuro-fuzzy inference system (ANFIS). The prediction of strength with the tool was agreeable with the experimental strength with the minimal error of less than 5%. This study concludes, that partial replacement of cement and coarse aggregate by seashell waste enhances the mechanical properties of the concrete significantly and enable proper utilization of these seashell waste as sustainable material for the concrete.

Abstract Introduction The COVID-19 pandemic impacted the operationalisation of non-COVID-19 clinical trials globally, particularly site and participant recruitment and trial success/stoppage. Trials which anticipate recruitment challenges may embed methods such as the QuinteT Recruitment Intervention (QRI) to help identify and understand the sources of challenges. Such interventions can help shed light on pandemic-related challenges. This paper reports our experience of the impact of the COVID-19 pandemic on conducting clinical trials with an embedded QRI, highlighting how the QRI aided in identifying challenges and potential solutions, particularly related to the site set-up and participant recruitment. Main body We report on 13 UK clinical trials which included a QRI. Information is from QRI data and researchers’ experience and reflections. In most trials, recruitment was lower than even the lowest anticipated rates. The flexibility of the QRI facilitated rapid data collection to understand and document, and in some instances respond to, operational challenges. Challenges were mostly logistical, pandemic-related and beyond the control of the site or central trial teams. Specifically: disrupted and variable site opening timelines —often due to local research and development (R&D) delays— shortages of staff to recruit patients; fewer eligible patients or limited access to patients; and intervention-related factors. Almost all trials were affected by pandemic-related staffing issues including redeployment, prioritisation of COVID-19 care and research, and COVID-19-related staff illness and absence. Trials of elective procedures were particularly impacted by the pandemic, which caused changes to care/recruitment pathways, deprioritisation of services, reduced clinical and surgical capacity and longer waiting lists. Attempted solutions included extra engagement with staff and R&D departments, trial protocol changes (primarily moving online) and seeking additional resourcing. Conclusion We have highlighted wide-ranging, extensive and consistent pandemic-related challenges faced by UK clinical trials, which the QRI helped to identify and, in some cases, address. Many challenges were insurmountable at individual trials or trials unit level. This overview highlights the need to streamline trial regulatory processes, address staffing crises, improve recognition of NHS research staff and for clearer, more nuanced central guidance on the prioritisation of studies and how to deal with the backlog. Pre-emptively embedding qualitative work and stakeholder consultation into trials with anticipated difficulties, moving some processes online, and flexible trial protocols may improve the resilience of trials in the current challenging context.

Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone–hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future.

Abstract Background Recruiting patients to randomised controlled trials (RCTs) is often reported to be challenging, and the evidence base for effective interventions that could be used by staff (recruiters) undertaking recruitment is lacking. Although the experiences and perspectives of recruiters have been widely reported, an evidence synthesis is required in order to inform the development of future interventions. This paper aims to address this by systematically searching and synthesising the evidence on recruiters’ perspectives and experiences of recruiting patients into RCTs. Methods A qualitative evidence synthesis (QES) following Thomas and Harden’s approach to thematic synthesis was conducted. The Ovid MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, ORRCA and Web of Science electronic databases were searched. Studies were sampled to ensure that the focus of the research was aligned with the phenomena of interest of the QES, their methodological relevance to the QES question, and to include variation across the clinical areas of the studies. The GRADE CERQual framework was used to assess confidence in the review findings. Results In total, 9316 studies were identified for screening, which resulted in 128 eligible papers. The application of the QES sampling strategy resulted in 30 papers being included in the final analysis. Five overlapping themes were identified which highlighted the complex manner in which recruiters experience RCT recruitment: (1) recruiting to RCTs in a clinical environment, (2) enthusiasm for the RCT, (3) making judgements about whether to approach a patient, (4) communication challenges, (5) interplay between recruiter and professional roles. Conclusions This QES identified factors which contribute to the complexities that recruiters can face in day-to-day clinical settings, and the influence recruiters and non-recruiting healthcare professionals have on opportunities afforded to patients for RCT participation. It has reinforced the importance of considering the clinical setting in its entirety when planning future RCTs and indicated the need to better normalise and support research if it is to become part of day-to-day practice. Trial registration PROSPERO CRD42020141297 (registered 11/02/2020).

Liver cirrhosis poses a global health challenge marked by significant prevalence and mortality. Current therapeutic options are limited by high costs and immune-mediated rejection, necessitating the exploration of innovative strategies to enhance hepatic self-rehabilitation, and counteract the underlying pathological mechanisms. We evaluated the hepatoprotective activity of rat adipose-derived mesenchymal stem cells (ADMSCs) in combination with platelet-rich plasma (PRP) and recombinant human hepatocyte growth factor (rh-HGF) on a rat model of liver fibrosis/cirrhosis induced by bile duct ligation (BDL). Treatment with PRP or rh-HGF alone did not yield significant hepatoprotection in the BDL-induced liver cirrhosis model. However, ADMSC transplantation alone exhibited the potential to alleviate impaired liver conditions. The combination of PRP and rh-HGF demonstrated superior ameliorative effects compared to either treatment alone. Notably, the combination of ADMSC + PRP or ADMSC + rh-HGF significantly enhanced hepatoprotective capacity compared to individual or combined PRP and rh-HGF therapies. Injection of ADMSC via the tail vein reduced inflammation, hepatocyte damage, and collagen deposition, improving overall liver function. This improvement was more pronounced when ADMSC was administered with PRP and rh-HGF versus monotherapy. Our study concludes that ADMSCs exert antifibrotic effects by inhibiting hepatic stellate cell proliferation, collagen synthesis, and inducing apoptosis. ADMSCs also demonstrate immune-modulatory effects and transdifferentiate into hepatic progenitor cells, secreting trophic factors, cytokines, and chemokines that promote impaired liver regeneration. The observed arrest in liver fibrosis progression highlights the potential therapeutic impact of these interventions.

Groundwater, found beneath the Earth’s surface in saturated zones of soil, sediment, and rock, plays a crucial role in sustaining ecosystems and supporting human activities like agriculture and industry. Monitoring and managing groundwater resources are crucial for sustainable use. As of the latest update in January 2022, Chennai, a city in southern India, has been grappling with water scarcity issues. The city has faced recurrent water shortages due to various factors, including rapid urbanization, inadequate infrastructure, depleting groundwater levels, and irregular rainfall patterns. Chengalpattu district in Tamil Nadu, India, is known for its diverse geographical features, incorporating urban and rural landscapes, and is significant for agriculture and water resource management. This study focuses on predicting variations in groundwater levels in open wells at different locations in the Chengalpattu district, assessing the effectiveness of various machine-learning models. This paper utilizes the ARIMA model provided by the stats models library. This library is widely employed for statistical modelling and hypothesis testing in Python, and encompasses a range of tools for time series analysis, including the ARIMA model. In this context. ARIMA models are employed for predicting future depth which focus on depicting autocorrelations in the data. Additionally, a package consolidating various models, including Seasonal Naïve (a straightforward forecasting method for seasonal data that serves as a reliable benchmark by relying on the observation from the same period a season ago), was incorporated in this study.

Abstract Background Many randomised controlled trials (RCTs) struggle to recruit, despite valiant efforts. The QRI (QuinteT Recruitment Intervention) uses innovative research methods to optimise recruitment by revealing previously hidden barriers related to the perceptions and experiences of recruiters and patients, and targeting remedial actions. It was designed to be integrated with RCTs anticipating difficulties at the outset. A new version of the intervention (QRI-Two) was developed for RCTs already underway with enrolment shortfalls. Methods QRIs in 12 RCTs with enrolment shortfalls during 2007–2017 were reviewed to document which of the research methods used could be rapidly applied to successfully identify recruitment barriers. These methods were then included in the new streamlined QRI-Two intervention which was applied in 20 RCTs in the USA and Europe during 2018–2019. The feasibility of the QRI-Two was investigated, recruitment barriers and proposed remedial actions were documented, and the QRI-Two protocol was finalised. Results The review of QRIs from 2007 to 2017 showed that previously unrecognised recruitment barriers could be identified but data collection for the full QRI required time and resources usually unavailable to ongoing RCTs. The streamlined QRI-Two focussed on analysis of screening/accrual data and RCT documents (protocol, patient-information), with discussion of newly diagnosed barriers and potential remedial actions in a workshop with the RCT team. Four RCTs confirmed the feasibility of the rapid application of the QRI-Two. When the QRI-Two was applied to 14 RCTs underway with enrolment shortfalls, an array of previously unknown/underestimated recruitment barriers related to issues such as equipoise, intervention preferences, or study presentation was identified, with new insights into losses of eligible patients along the recruitment pathway. The QRI-Two workshop enabled discussion of the newly diagnosed barriers and potential remedial actions to improve recruitment in collaboration with the RCT team. As expected, the QRI-Two performed less well in six RCTs at the start-up stage before commencing enrolment. Conclusions The QRI-Two can be applied rapidly, diagnose previously unrecognised recruitment barriers, and suggest remedial actions in RCTs underway with enrolment shortfalls, providing opportunities for RCT teams to develop targeted actions to improve recruitment. The effectiveness of the QRI-Two in improving recruitment requires further evaluation.

Abstract Recently, hydrothermal carbonization emerges as the most viable option for the management of solid waste with high moisture content. Sludge derived hydrochar is used as an adsorbent for emerging contaminants or micro-pollutants in the domain of sustainability. Current study demonstrates the KOH activation of hydrochar produced from paper board mill sludge and evaluates its removal potential of a Non-steroidal anti-inflammatory drug, Diclofenac from aqueous solution. The activated hydrochars exhibited porous, spherical micro-structures with higher fraction of oxygenated functional groups paving way for the efficient adsorption of Diclofenac. The effect of initial Diclofenac concentration and contact time was ascertained using adsorption kinetics and isotherms. The adsorption kinetics exhibited second-order reaction for all adsorbents indicating higher coefficient of determination (R2 > 0.9). The Diclofenac adsorption on hydrochars followed Langmuir isotherm model with the post-activated hydrochar recording a highest adsorption capacity of 37.23 mg g−1 in 40 mg L−1 initial Diclofenac concentration at 15 h equilibrium time.

Background: Lung cancer is the leading cause of cancer death. Surgery remains the main method of managing early-stage disease. Minimal-access video-assisted thoracoscopic surgery results in less tissue trauma than open surgery; however, it is not known if it improves patient outcomes. Objective: To compare the clinical effectiveness and cost-effectiveness of video-assisted thoracoscopic surgery lobectomy with open surgery for the treatment of lung cancer. Design, setting and participants: A multicentre, superiority, parallel-group, randomised controlled trial with blinding of participants (until hospital discharge) and outcome assessors conducted in nine NHS hospitals. Adults referred for lung resection for known or suspected lung cancer, with disease suitable for both surgeries, were eligible. Participants were followed up for 1 year. Interventions: Participants were randomised 1 : 1 to video-assisted thoracoscopic surgery lobectomy or open surgery. Video-assisted thoracoscopic surgery used one to four keyhole incisions without rib spreading. Open surgery used a single incision with rib spreading, with or without rib resection. Main outcome measures: The primary outcome was self-reported physical function (using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30) at 5 weeks. Secondary outcomes included upstaging to pathologic node stage 2 disease, time from surgery to hospital discharge, pain in the first 2 days, prolonged pain requiring analgesia at > 5 weeks, adverse health events, uptake of adjuvant treatment, overall and disease-free survival, quality of life (Quality of Life Questionnaire Core 30, Quality of Life Questionnaire Lung Cancer 13 and EQ-5D) at 2 and 5 weeks and 3, 6 and 12 months, and cost-effectiveness. Results: A total of 503 patients were randomised between July 2015 and February 2019 (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 256). One participant withdrew before surgery. The mean age of patients was 69 years; 249 (49.5%) patients were men and 242 (48.1%) did not have a confirmed diagnosis. Lobectomy was performed in 453 of 502 (90.2%) participants and complete resection was achieved in 429 of 439 (97.7%) participants. Quality of Life Questionnaire Core 30 physical function was better in the video-assisted thoracoscopic surgery group than in the open-surgery group at 5 weeks (video-assisted thoracoscopic surgery, n = 247; open surgery, n = 255; mean difference 4.65, 95% confidence interval 1.69 to 7.61; p = 0.0089). Upstaging from clinical node stage 0 to pathologic node stage 1 and from clinical node stage 0 or 1 to pathologic node stage 2 was similar (p ≥ 0.50). Pain scores were similar on day 1, but lower in the video-assisted thoracoscopic surgery group on day 2 (mean difference –0.54, 95% confidence interval –0.99 to –0.09; p = 0.018). Analgesic consumption was 10% lower (95% CI –20% to 1%) and the median hospital stay was less (4 vs. 5 days, hazard ratio 1.34, 95% confidence interval 1.09, 1.65; p = 0.006) in the video-assisted thoracoscopic surgery group than in the open-surgery group. Prolonged pain was also less (relative risk 0.82, 95% confidence interval 0.72 to 0.94; p = 0.003). Time to uptake of adjuvant treatment, overall survival and progression-free survival were similar (p ≥ 0.28). Fewer participants in the video-assisted thoracoscopic surgery group than in the open-surgery group experienced complications before and after discharge from hospital (relative risk 0.74, 95% confidence interval 0.66 to 0.84; p

Background: Due to the high prevalence of oral and maxillofacial (OMF) trauma in city of Riyadh, a special focus on pediatric trauma is needed. The purpose of this audit was to assess the protocol followed by the OMF unit at King Khalid University Hospital (KKUH) on pediatric trauma patients. The trauma incidence, mechanism of injury, volume, the type of pediatric trauma operated and dental management were analyzed. Materials and Methods: A quantitative retrospective review of 223 patients, at pediatric emergency unit of KKUH, Riyadh, KSA from January 2017 to July 2018, was done. The data retrieved included variables such as, age, gender, and cause of injury, site of injury, type of injury, and assessment of jaws, and teeth. Data regarding the type of investigations, treatment protocol, follow up visit, and dental management, were extracted from the medical records. Results: Of the 223 pediatric patients presenting to the emergency unit, 116 (52%) were under the age of 5 years. A total of 64.4% of patients reported “self-fall” as the cause of injury. Soft-tissue injuries were common in 63 (56.8%) of patients in the form of lacerations 87 (41.2%). Involvement of the teeth in the injury was observed in 57 patients, in which 33 (57.9%) patients were reported to have tooth/teeth avulsions, 15 (26.3%) patients had luxation and 9 (15.8%) patients had crown fractures. 27 (47%) patients were referred to the pedodontist for a follow-up visit. Conclusions: It can concluded that clinicians facing maxillofacial trauma in an emergency department need to have access to useful and practice guidelines. The study also showed the need for more manpower-oriented training such as a pedodontist and a general dentist to join the OMFS team to manage pediatric patients. The regional referral hospitals should be equipped to decentralize the management of these patients to the Dental University Hospital.

Objective To review guidance, included in written local UK National Health Service (NHS) organisation policies, on information provision and consent for the introduction of new invasive procedures- including surgeries, and devices (IPs/Ds).Design A qualitative documentary analysis of data on patient information provision and consent extracted from policies for the introduction of IP/Ds from NHS organisations in England and Wales.Setting NHS trusts in England and health boards in Wales, UK.Participants Between December 2017 and July 2018, 150 acute trusts in England and 7 health boards in Wales were approached for their policies for the introduction of new IP/Ds. In total, 123 policies were received, 11 did not fit the inclusion criteria and a further policy was included from a trust website resulting in 113 policies included for review.Results From the 113 policies, 22 did not include any statements on informed consent/information provision or lacked guidance on the information to be provided to patients and were hence excluded. Consequently, 91 written local NHS policies were included in the final dataset. Within the guidance obtained, variation existed on disclosure of the procedure’s novelty, potential risks, benefits, uncertainties, alternative treatments and surgeon’s experience. Few policies stated that clinicians should discuss the existing evidence associated with a procedure. Additionally, while the majority of policies referred to patients needing written information, this was often not mandated and few policies specified the information to be included.Conclusions Nearly a fifth of all the policies lacked guidance on information to be provided to patients. There was variability in the policy documents regarding what patients should be told about innovative procedures. Further research is needed to ascertain the information and level of detail appropriate for patients when considering innovative procedures. A core information set including patients’ and clinicians’ views is required to address variability around information provision/consent for innovative procedures.

Abstract Background Many people with spinal cord injury (SCI) have limited access to tailored, readily available exercise resources. As a result, exercise remains an underutilized treatment strategy for improving health and function in people with SCI. The purpose of this study is to test the effectiveness of two remotely delivered exercise programs for people with SCI. Methods The Spinal Cord Injury Program in Exercise (SCIPE) study is a three-arm adaptive randomized controlled trial examining two 8-week teleexercise interventions: Movement-to-Music (M2M) and Standard Exercise Training (SET), compared to Attention Control (AC) in 327 adults with SCI. The primary outcome is change in physical activity level at post 8-week intervention. The study contains two interim analyses. The first interim analysis will assess feasibility metrics of the protocol after 36 participants complete the 8-week intervention period. The second interim analysis will examine two effectiveness comparisons: SET vs. AC and M2M vs AC, after 165 participants complete the intervention period. Early termination of the intervention arm(s) will take place when non-significant findings are found in the corresponding intervention(s). Incorporation of such interim analysis enhances trial efficiency by dropping the intervention(s) that deemed ineffective. It provides ethical benefits and allows allocation of additional resources to explore the effective intervention(s). Discussion Delivery of teleexercise programs may be an effective strategy for addressing transportation barrier to exercise resources and increasing physical activity level and quality of life in people with SCI. Trial registration ClinicalTrials.gov Identifier NCT03925077 . Registered trial name: Spinal Cord Injury Program in Exercise (SCIPE). Registered on April 23rd, 2019.

Type 2 diabetes mellitus (T2DM) is characterized by impaired insulin secretion on a background of insulin resistance (IR). IR and T2DM are associated with atherosclerotic coronary artery disease (CAD). The mechanisms of IR and atherosclerosis are known to share similar genetic and environmental roots. Endothelial dysfunction (ED) detected at the earliest stages of IR might be the origin of atherosclerosis progression. ED influences the secretion of pro-inflammatory cytokines and their encoding genes. The genes and their single nucleotide polymorphisms (SNPs) act as potential genetic markers of IR and atherosclerosis. This review focuses on the link between IR, T2DM, atherosclerosis, CAD, and the potential genetic markers CHI3L1, CD36, LEPR, RETN, IL-18, RBP-4, and RARRES2 genes.

Small‐cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next‐generation sequencing (NGS) and by characterizing a representative patient‐derived model. We performed targeted NGS, as well as comprehensive pathological evaluation, in 11 never/former light smokers with clinically diagnosed SCLC. We established a patient‐derived model from one such patient (DFCI168) harboring an NRASQ61K mutation and characterized the sensitivity of this model to MEK and TORC1/2 inhibitors. Despite the clinical diagnosis of SCLC, the majority (8/11) of cases were either of nonpulmonary origin or of mixed histology and included atypical carcinoid (n = 1), mixed non‐small‐cell lung carcinoma and SCLC (n = 4), unspecified poorly differentiated carcinoma (n = 1), or small‐cell carcinoma from different origins (n = 2). RB1 and TP53 mutations were found in four and five cases, respectively. Predicted driver mutations were detected in EGFR (n = 2), NRAS (n = 1), KRAS (n = 1), BRCA1 (n = 1), and ATM (n = 1), and one case harbored a TMPRSS2‐ERG fusion. DFCI168 (NRASQ61K) exhibited marked sensitivity to MEK inhibitors in vitro and in vivo. The combination of MEK and mTORC1/2 inhibitors synergized to prevent compensatory mTOR activation, resulting in prolonged growth inhibition in this model and in three other NRAS mutant lung cancer cell lines. SCLC in never/former light smokers is rare and is potentially a distinct disease entity comprised of oncogenic driver mutation‐harboring carcinomas morphologically and/or clinically mimicking SCLC. Comprehensive pathologic review integrated with genomic profiling is critical in refining the diagnosis and in identifying potential therapeutic options.

There is insufficient data to assess the effects of any of the different management strategies for recurrent or persistent stress urinary incontinence in women after failed interventional treatment. The evidence base lacks well-designed randomised trials with sufficient power to answer this hugely important issue. PURSUIT is the Proper Understanding of Recurrent Stress Urinary Incontinence Treatment study, assessing through randomisation whether endoscopic or surgical interventions achieve better cure and/or quality of life outcomes at 1 year, and will follow up to 3 years to see if responses are sustained. The manuscript provides an outline of the study, describes the challenges it has faced, and advocates the importance of ensuring its successful delivery.

Despite their role as innate sentinels, macrophages can serve as cellular reservoirs of chikungunya virus (CHIKV), a highly-pathogenic arthropod-borne alphavirus that has caused large outbreaks among human populations. Here, with the use of viral chimeras and evolutionary selection analysis, we define CHIKV glycoproteins E1 and E2 as critical for virion production in THP-1 derived human macrophages. Through proteomic analysis and functional validation, we further identify signal peptidase complex subunit 3 (SPCS3) and eukaryotic translation initiation factor 3 subunit K (eIF3k) as E1-binding host proteins with anti-CHIKV activities. We find that E1 residue V220, which has undergone positive selection, is indispensable for CHIKV production in macrophages, as its mutation attenuates E1 interaction with the host restriction factors SPCS3 and eIF3k. Finally, we show that the antiviral activity of eIF3k is translation-independent, and that CHIKV infection promotes eIF3k translocation from the nucleus to the cytoplasm, where it associates with SPCS3. These functions of CHIKV glycoproteins late in the viral life cycle provide a new example of an intracellular evolutionary arms race with host restriction factors, as well as potential targets for therapeutic intervention.

The usefulness of fibre reinforced concrete (FRC) in various civil engineering applications is indisputable. Fibre reinforced concrete has been successfully used so far in construction of structures like bridges, industrial structures, concrete, architectural panels, precast products, offshore structures and many other applications. This paper presents the study on the mechanical properties of the polypropylene fibre reinforced concrete. The parameters varied in the study include volume of fibre (0%, 0.5%, 1.0%, 1.5% & 2.0%) and the curing period (7 days and 14 days). From the study it is concluded that the further increases in the volume of fibre reduces the water cement ratio. The mechanical properties of the polypropylene fibre reinforced concrete were also predicted by using Artificial Neural Network (ANN) and found to have minimal error when compared to actual experimental results.

BackgroundA common leisure-time activity amongst youth and adults in the United States is video gameplay. Playing video games is typically a sedentary endeavor; however, to encourage an increased level of physical activity in an engaging and enjoyable way, active video gaming has become popular. Unfortunately, the accessibility of gaming controllers is often an issue for persons with disabilities. A commercial off-the-shelf (OTS) gaming mat was adapted to facilitate use by individuals with mobility impairments to address this issue. ObjectiveOur study aimed to examine energy expenditure, enjoyment, and gameplay experience in youth and adults with mobility impairment during active video gaming using an OTS and adapted versions of a gaming mat. MethodsThe study used an observational design. During visit 1, physical function was assessed, and participants were given a familiarization period with the gaming system. For visit 2, based on observation during the physical function tests and discussion with the participant, it was decided whether the participant would play in a standing or seated position. For standing gameplay, the mat was placed on the floor, and for seated play, the mat was placed on a height-adjustable and tilt-adjustable tabletop. Metabolic data were collected during a 20-minute baseline and four 10-minute bouts of Wii Fit Plus gameplay, with 2 bouts on each of the mats (adapted and OTS). During gameplay, the research staff observed and rated participants’ ability to use the game controller (mat) and the quality of gameplay. At the end of each game set, participants reported their rating of perceived exertion on a scale from 0 to 10. During rest, participants completed the physical activity enjoyment scale. Participants also answered additional questions regarding the system's usability with each controller (adapted mat and OTS mat). Statistical analyses were computed using Stata 16 (version 16.1; StataCorp). Linear mixed-effects maximum likelihood regression was performed separately for individuals who could play standing and for those who played seated. ResultsA convenience sample of 78 individuals with mobility impairments between the ages of 12 and 60 years (mean 39.6, SD 15.8) participated in the study. Of the sample, 48 participants played the video games in a seated position, while 30 played the games standing. Energy expenditure and heart rate tended to be higher in the OTS mat condition for seated players, while values were similar for both conditions among standing players. However, seated participants reported greater gameplay experience, and both groups exhibited a higher quality of gameplay during the adapted mat condition. ConclusionsActive video gaming using an adapted gaming mat provided an enjoyable exercise activity for individuals with mobility impairments. The use of the adapted controller provides a means by which this population can engage in light to moderate intensity active video gaming, thereby reducing sedentary leisure time. Trial RegistrationClinicalTrials.gov NCT02994199; https://clinicaltrials.gov/ct2/show/NCT02994199

Objectives COVID-19 presents a risk of infection and transmission for operating theatre teams. Guidelines to protect patients and staff emerged and changed rapidly based on expert opinion and limited evidence. This paper presents the experiences and innovations developed by international surgical teams during the early stages of the pandemic to attempt to mitigate risk.Design In-depth, semistructured interviews were audio recorded, transcribed and analysed thematically using methods of constant comparison.Participants 43 participants, including surgeons from a range of specialties (primarily general surgery, otolaryngology, neurosurgery, cardiothoracic and ophthalmology), anaesthetists and those in nursing roles.Setting The UK, Italy, Spain, the USA, China and New Zealand between March and May 2020.Results Surgical teams sought to mitigate COVID-19 risks by modifying their current practice with an abundance of strategies and innovations. Communication and teamwork played an integral role in how teams adapted, although participants reflected on the challenges of having to improvise in real time. Uncertainties remained about optimal surgical practice and there were significant tensions where teams were forced to balance what was best for patients while contemplating their own safety.Conclusions The perceptions of risks during a pandemic such as COVID-19 can be complex and context dependent. Management of these risks in surgery must be driven by evidence‐based practice resulting from a pragmatic and novel approach to collation of global evidence. The context of surgery has changed dramatically, and surgical teams have developed a plethora of innovations. There is an urgent need for high-quality evidence to inform surgical practice that optimises the safety of both patients and healthcare professionals as the COVID-19 pandemic unfolds.

Groundnut TMV 14 is high yielding Spanish bunch genotype. It is the cross derivative of VRI 6 x R 2001-(2) through pedigree method of breeding Groundnut TMV 14 (2124 kg/ha) has given higher pod yield over the check varieties; 11.5 % increase over VRI (Gn) 6 (1904kg/ha); 15.2 % over check variety TMV Gn 13 (1844 kg/ha) during Kharif season. Groundnut TMV 14 (2286 kg/ha) has given higher pod yield over the check varieties; 29.7 % increase over VRI(Gn)6 (1762kg/ha); 32.3 % over check variety TMV Gn 13 (1727kg/ha) during rabi season under irrigated condition.For oil yield during Kharif season (720 kg/ha), variety TMV 14 gave 14.6%(720kg/ha)increase over VRI(Gn)6 (628kg/ha); 10.7 % over TMV Gn 13 (650 kg/ha) during Kharif season. Similarly for oil yield during rabi season under irrigated condition(775 kg/ha), variety TMV 14 gave 33.3% increase over VRI(Gn)6 (581 kg/ha); 27.2 % over TMV Gn 13 (609 kg/ha).For dry haulm yield (3640 kg/ha), variety TMV 14 gave 12.3% increase over VRI(Gn)6 (3240kg/ha); 22.6 % over TMV Gn 13 (2970 kg/ha) during Kharif season. For dry haulm yield (3758 kg/ha) the variety TMV 14 gave 13.02% increase over VRI(Gn)6 (3326kg/ha); 4.03 % over TMV Gn 13 (3604 kg/ha) during rabi under irrigated condition. Shelling turnover of TMV 14 (70.6%) comparable with VRI(Gn)6 (68%). Sound Mature Kernels are more in TMV 14 (93.9%) compared to VRI(Gn)6 (92%). 100 kernel weight are more in TMV 14 (38g) compared to VRI(Gn)6 (35.0) and TMV Gn 13( 34.6).The variety TMV 14 matures early in 95-100days.For Late leaf spot and rust diseases, variety TMV 14 has shown moderated resistance incidence compared to check varieties.TMV 14 has shown tolerance against Spodoptera litura, thrips and Heliathis armigera and leaf miner.

Herpes zoster ophthalmicus is commonly used to describe viral reactivation from the trigeminal ganglia with ocular involvement. The ophthalmic branch is the most commonly involved, whereas the maxillary and mandibular dermatomes are less commonly affected. Neurotrophic ulcer may occur secondary to intentional or inadvertent damage to the trigeminal nucleus, root, ganglion, or any segment of the ophthalmic branch of this cranial nerve. We report a case of reactivated maxillary herpes zoster combined with neurotrophic keratitis due to percutaneous 2nd and 3rd branch of trigeminal nerve block with alcohol to treat trigeminal neuralgia. A 57-year-old female came to the ophthalmology department complaining of decreased visual acuity and skin vesicle over the right lower lid and cheek. She had undergone right trigeminal nerve block for treatment of trigeminal neuralgia. Clinical examination revealed neurotrophic keratitis and maxillary herpes zoster. She was treated with oral and topical antivirals and vigorous lubrication with eye drops. Her neurotrophic keratitis showed a slow recovery. Although a few cases of herpes zoster following nerve block have been described, it would appear that a case of simultaneous maxillary herpes zoster and neurotrophic keratitis following trigeminal block has not yet been documented. It is possible that trigeminal nerve block may cause reactivation of latent virus and refractory neurotrophic keratitis.

Abstract Background Tumor orchestrated metabolic changes in the microenvironment limit generation of anti-tumor immune responses. Availability of arginine, a semi-essential amino acid, is critical for lymphocyte proliferation and function. Levels of arginine are regulated by the enzymes arginase 1,2 and nitric oxide synthase (NOS). However, the role of arginase activity in lung tumor maintenance has not been investigated in clinically relevant orthotopic tumor models. Methods RNA sequencing (RNA-seq) of sorted cell populations from mouse lung adenocarcinomas derived from immunocompetent genetically engineered mouse models (GEMM)s was performed. To complement mouse studies, a patient tissue microarray consisting of 150 lung adenocarcinomas, 103 squamous tumors, and 54 matched normal tissue were stained for arginase, CD3, and CD66b by multiplex immunohistochemistry. Efficacy of a novel arginase inhibitor compound 9 in reversing arginase mediated T cell suppression was determined in splenocyte ex vivo assays. Additionally, the anti-tumor activity of this compound was determined in vitro and in an autochthonous immunocompetent KrasG12D GEMM of lung adenocarcinoma model. Results Analysis of RNA-seq of sorted myeloid cells suggested that arginase expression is elevated in myeloid cells in the tumor as compared to the normal lung tissue. Accordingly, in the patient samples arginase 1 expression was mainly localized in the granulocytic myeloid cells and significantly elevated in both lung adenocarcinoma and squamous tumors as compared to the controls. Our ex vivo analysis demonstrated that myeloid derived suppressor cell (MDSC)s cause T cell suppression by arginine depletion, and suppression of arginase activity by a novel ARG1/2 inhibitor, compound 9, led to restoration of T cell function by increasing arginine. Treatment of KrasG12D GEMM of lung cancer model with compound 9 led to a significant tumor regression associated with increased T cell numbers and function, while it had no activity across several murine and human non-small cell (NSCLC) lung cancer lines in vitro. Conclusions We show that arginase expression is elevated in mouse and patient lung tumors. In a KRASG12D GEMM arginase inhibition diminished growth of established tumors. Our data suggest arginase as an immunomodulatory target that should further be investigated in lung tumors with high arginase activity.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease process where the exact pathogenesis is not known. It is an independent immunological condition affecting multiple organ systems. Major manifestations include chronic urticarial vasculitis (UV) with complement deficiency and demonstration of serum C1q antibodies. We describe a case of a 60-year-old male who presented with a generalized rash and was eventually diagnosed with HUVS. Usually, HUVS and systemic lupus erythematosus (SLE) have overlapping features, and our case was unique as our patient did not have any SLE manifestations. This article emphasizes the importance of comprehensive review of systemic manifestations accompanying UV. Although rare, it raises the awareness among the physicians about its clinical presentation and diagnostic approach and also predicts the prognosis of the same.

Background: Stress is an unavoidable part of our life. Certain amount of stress is needed for our survival. Stress is one of the factors, which affects the health and eating habits of a person. Objectives: The aim of the study was to compare the perceived stress among professional and nonprofessional undergraduate students and to find out the relationship between eating behavior and perceived stress of undergraduate students. Methods: A comparative descriptive study was conducted from November 2017 to April 2018, among 400 undergraduate students from selected professional and nonprofessional colleges in Udupi District, Karnataka. Students were recruited using proportionate sampling technique. Data were collected using a self-administered questionnaire after obtaining informed consent of the study participants. Results: Statistically significant difference was found in perceived stress of professional and nonprofessional students (Z = −2.397, P = 0.017). There was a weak positive correlation between perceived stress and uncontrolled eating of professional students (ρ= 0.162, P = 0.022) and nonprofessional students (ρ= 0.183, P = 0.009). There was no association found between perceived stress and selected demographic variables such as age, gender, study course, year of study, type of family, and occupation of parents (P > 0.05). Conclusions: Perceived stress of professional students is more compared to nonprofessional students. Uncontrolled eating behavior is influenced by increase in stress, and perceived stress is independent of demographic variables.

Introduction The post-2005 rise in clinical trials and clinical research conducted in India was accompanied by frequent reports of unethical practices, leading to a series of regulatory changes. We conducted a systematic scoping review to obtain an overview of empirical research pertaining to the ethics of clinical trials/research in India.Methods Our search strategy combined terms related to ethics/bioethics, informed consent, clinical trials/research and India, across nine databases, up to November 2019. Peer-reviewed research exploring ethical aspects of clinical trials/research in India with any stakeholder groups was included. We developed an evidence map, undertook a narrative synthesis and identified research gaps. A consultation exercise with stakeholders in India helped contextualise the review and identify additional research priorities.Results Titles/Abstracts of 9699 articles were screened, full text of 282 obtained and 80 were included. Research on the ethics of clinical trials/research covered a wide range of topics, often conducted with little to no funding. Studies predominantly examined what lay (patients/public) and professional participants (eg, healthcare staff/students/faculty) know about topics such as research ethics or understand from the information given to obtain their consent for research participation. Easily accessible groups, namely ethics committee members and healthcare students were frequently researched. Research gaps included developing a better understanding of the recruitment-informed consent process, including the doctor-patient interaction, in multiple contexts and exploring issues of equity and justice in clinical trials/research.Conclusion The review demonstrates that while a wide range of topics have been studied in India, the focus is largely on assessing knowledge levels across different population groups. This is a useful starting point, but fundamental questions remain unanswered about informed consent processes and broader issues of inequity that pervade the clinical trials/research landscape. A priority-setting exercise and appropriate funding mechanisms to support researchers in India would help improve the clinical trials/research ecosystem.

The diagnosis of giant cell arteritis (GCA) when presenting with atypical features such as stroke is very challenging. Only 0.17% of first-ever strokes are caused by GCA, a life-threatening condition when left untreated. Very few cases have been reported on giant cell arteritis leading to acute stroke due to vertebral artery dissection. We present a case of a 76-year-old female with no medical history who presented with sudden onset right visual loss and left hemiparesis. She had been initially treated for acute stroke and upon further workup was found to have left vertebral artery dissection. She had erythrocyte sedimentation rate (ESR) of 71 mm/h, and bilateral temporal artery biopsy was consistent with giant cell arteritis. Patient received high doses of methylprednisolone which resolved her hemiparesis, but her vision loss did not improve. Stroke in the presence of significant involvement of vertebral arteries should raise suspicion of GCA especially if classic symptoms preceded stroke event. High clinical suspicion is required to prevent delay in diagnosis and treatment.