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This case study explores the use of super-dose platelet-rich plasma (PRP) in managing a meniscal tear in a 43-year-old woman with left knee pain. The patient was diagnosed with a vertical longitudinal tear of the body and posterior horn medial meniscus, confirmed through magnetic resonance imaging. Super-dose PRP, characterized by a higher platelet volume (8 ml), was administered intra-articular. Post-injection, the patient reported initial discomfort for a few days, but significant improvements in pain and range of motion (ROM) were observed within the first week. Over 12 weeks, her visual analog scale pain score decreased from 8/10 during activity to 2/10, and her ROM returned to full functionality. The case supports the hypothesis that super-dose PRP may enhance the healing process in meniscal injuries by promoting tissue healing and regeneration through the release of growth factors, angiogenesis, collagen synthesis, and inflammation modulation. This case highlights PRP's potential as a non-surgical treatment for meniscal tears. Further large-scale studies and randomized controlled trials are needed to validate these results, optimize dosing strategies, and determine which patient populations will benefit most from this innovative treatment approach., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thirugnana Sambandam et al.)

This case report explores the use of blood flow restriction (BFR) training to improve body composition in a 26-year-old male with L5-S1 disc protrusion and nerve root compression. BFR training, involving low-intensity exercises with restricted blood flow, offers a promising alternative for patients unable to engage in high-intensity workouts. The patient, a recreational gymgoer with a history of a significant lower back injury from a maximal deadlift event 20 months ago, presented with chronic pain, weight gain, and decreased stamina. Two attempts at spinal steroid injections during the 20-month period yielded only temporary relief, prompting the implementation of a 12-week BFR training regimen. The program combined BFR exercises with a calorie-deficit diet, resulting in substantial improvements in body composition and strength. Over 12 weeks, the patient lost 11.68 kg, reduced his body mass index from 26.50 to 22.85, and decreased his total body fat percentage from 28% to 22.43%. His lower back pain also significantly improved. This case highlights the effectiveness of BFR training in managing obesity and enhancing physical fitness in spinal injury patients, emphasizing the need for further research on its broader application., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Saveetha Medical College and Hospital Institutional Ethics committee issued approval N/A. The participant was explained about the potential benefits and risks associated with the treatment. It was brought to his knowledge that he would receive no monetary remuneration for this case study. He was also informed about the alternate available treatments. Post this information, he gave his willingness to receive the treatment by signing an informed consent form. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thirugnana Sambandam et al.)

Background: Despite extensive research on the relationship between psychological factors and aerobic training, there remains a gap in understanding these relationships within resistance training (RT), particularly barbell-based RT. This study aimed to examine the associations between basic psychological needs, behavioral regulation, self-efficacy, and a longitudinal barbell-based RT program for adults., Methods: Forty-three adults ( M age = 45.09 ± 10.72) were recruited from the Competitive Edge resistance training program at a medical fitness center in Northwest Montana. The study followed an 18-week schedule: 8 weeks of training, 1 week of active recovery, and 8 additional weeks of training., Results: The results reveal several significant findings. First, the basic psychological need for competence significantly increased from baseline ( M  = 5.06) to post-program ( M  = 5.30), ( p = 0.017). Second, the composite score of the BREQ-3 significantly predicting muscular strength improvements in the deadlift ( β  = 3.64, p  = 0.039). Third, both mastery ( p  = 0.021) and resilience ( p  = 0.007) self-efficacy subscales increased from baseline to post-program. Fourth, exploratory analyses indicated that the reasons to exercise scale predicted increases in muscular endurance with the weight management ( β  = 10.016, p  = 0.046) and solitude ( β  = 6.792, p  = 0.037) subscales., Conclusion: These findings highlight the importance of psychological factors in predicting strength outcomes and muscular endurance, suggesting that psychological interventions may complement physical training to maximize benefits. This research contributes valuable insights into how psychological factors influence training outcomes, potentially guiding future interventions and program designs to better support strength development and endurance in resistance training contexts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Martinez Kercher, Watkins, Goss, Phillips, Roy, Blades, Dobson and Kercher.)

Os vesalianum pedis (OVP) is one of the exquisite accessory ossicles adjacent to the foot's fifth metatarsal base. Though most of the OVP cases are asymptomatic, only a handful of patients who presented with lateral foot pain have been reported. A 36-year-old professional badminton player presented with swelling and tenderness in the right foot at the metatarsal base. An initial radiographic examination revealed a pseudo-Jones fracture. As a result of persistent pain and concerns regarding OVP, a reassessment of the X-ray was conducted. The examination revealed a radiolucent line with well-defined and well-corticated edges, uniformly separating the ossicle from the metatarsal in the right foot, consequently leading to the diagnosis of OVP. Following diagnosis, the patient was managed conservatively. Os vesalianum is not a common source of pain on the midfoot's lateral side. An oblique radiograph is an appreciable strategy to demonstrate the accessory ossicle. Thus, a careful clinical examination, coupled with the correlation of radiological findings, is a prerequisite to prevent misdiagnosis and overtreatment thereafter., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Roy Mohan et al.)

Introduction Heart rate variability (HRV) indexes the autonomic nervous system, and HRV values are found to be higher in elite badminton players. Since an athlete's agility has a direct influence on badminton sporting performance, this study will analyze the correlation between HRV and agility. Aim The study's primary aim is to analyze the correlation between HRV and agility scores of elite badminton players. Methodology Ten elite badminton players who are currently participating at the state and national levels were recruited for the study. The study's participants were aged between 18 and 21 years, had a body mass index (BMI) of less than 22.9 kg/m 2 , were currently training 10-12 sessions of badminton per week (120-180 minutes per session), and had no comorbidities, injuries, or illnesses. For a duration of 14 days, a cross-sectional study design was utilized to evaluate the badminton players. Participants were tested in two blocks; each block consisted of five days of HRV and agility testing (Southeast Missouri [SEMO] agility test) followed by a break for two days. Higher agility performance was reflected by a lower SEMO agility test score. Results Data were analyzed using IBM SPSS Statistics for Windows, Version 27.0 (IBM Corp., Armonk, NY). HRV and agility scores had a negative correlation, as indicated by the two-tailed Spearman correlation analysis ( r s (8) = -0.82, P < 0.01). Conclusions The results showed that HRV and agility scores are highly correlated in elite badminton players. The results indicate that higher HRV values lead to better agility performance. Future studies need to be conducted on a large scale to evaluate the correlation in a diverse population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Dominic et al.)

This article explores the technology underpinning the decentralized data revolution and encourages Indigenous Peoples (IPs) to secure their Indigenous Data Sovereignty (IDSov) over the Metaverse and Web3. More specifically, this article will survey blockchain technologies, exploring some disturbing colonial uses and providing an international legal framework that IPs can use to advance their IDSov internationally and domestically. This article will consider the role that cryptocurrencies, smart contracts, decentralized oracles, non-fungible tokens (NFTs), decentralized finance (DeFi), and decentralized autonomous organizations (DAOs) might play in advancing IDSov as it relates to western conceptualizations of Web3 and the Metaverse. The worldwide web's global data structure is undergoing a seismic shift that will significantly impact IPs. As inherent sovereigns, IPs are uniquely positioned to use and regulate these technologies in manners consistent with their cultural values and international indigenous human rights instruments. However, the march toward Web3 also looms menacingly over IPs. As such, we intend to examine IPs' novel risks and opportunities with Web3 and the Metaverse. We conclude by encouraging IPs to become fluent in the minutia of these technologies and to exert their inherent sovereignty over these nascent technologies in international and domestic arenas by building culturally informed systems to address their particularized needs. Future research should look toward the specific hurdles, and successes IPs are experiencing as they apply the technologies and principles discussed here., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dobson and Fernandez.)

Over recent decades, the arts have become a popular response to dementia. Amidst wider concerns with accessibility, widening participation and audience diversity, coupled with greater attention to creativity across dementia studies, many arts organisations are now offering dementia friendly initiatives. While dementia friendliness has been well-established for almost a decade, the meaning of friendliness remains vague. This paper reports results from a study of how stakeholders navigate this nebulousness when developing their own dementia friendly cultural events. To assess this, we interviewed stakeholders working for arts organisations in the northwest of England. We found that participants built up local informal networks of knowledge exchange, sharing experiences between stakeholders. The dementia friendliness that characterises this network centres on the crafting of vibes that enable people with dementia to 'unhide' themselves. Through this accommodating approach, dementia friendliness converges with stakeholder interests, becoming something of an art form in its own right, typified by active embodied experience, flexible and creative self-expression, and being in-the-moment.

The expansion of the therapeutic armamentarium available to oncologists and haematologists has led to a significant improvement in cancer survival; however, many of the available treatments carry a risk of toxicity to the heart. Cardio-oncology has emerged as a rapidly developing subspeciality dedicated to improving the cardiovascular care of patients before, during and after cancer treatment. The 2022 European Society of Cardiology guidelines on cardio-oncology provide a comprehensive overview of best-practice recommendations for cardiovascular care aimed at healthcare professionals treating cancer patients. The main focus of the guidelines is to ensure patients can complete their cancer treatment without significant cardiotoxicity and the correct follow-up for the first 12 months following treatment and beyond is instituted. The guidelines provide harmonisation of baseline risk stratification and toxicity definitions and encompass recommendations for all the major classes of therapy used in modern oncology and haematology. This review summarises the key points from the guidelines document., Competing Interests: Disclosure: RD reports lecture fees outside of this work from Bristol Myers Squibb, Roche Diagnostics and Servier and is on the European Cardiology Review editorial board; this did not influence peer review. DG has no conflicts of interest to declare. Authors’ contributions: DGG and RD co-wrote the manuscript., (Copyright © 2023, Radcliffe Cardiology.)

Newborns in high-income countries are routinely screened for neonatal jaundice using transcutaneous bilirubinometery (TcB). In low-and middle-income countries, TcB is not widely used due to a lack of availability; however, mobile-phone approaches for TcB could help expand screening opportunities. We developed a mobile phone-based approach for TcB and validated the method with a 37 patient multi-ethnic pilot study. We include a custom-designed snap-on adapter that is used to create a spatially resolved diffuse reflectance detection configuration with the illumination provided by the mobile-phone LED flash. Monte-Carlo models of reflectance from neonatal skin were used to guide the design of an adapter for filtered red-green-blue (RGB) mobile-phone camera reflectance measurements. We extracted measures of reflectance from multiple optimized spatial-offset regions-of-interest (ROIs) and a linear model was developed and cross-validated. This resulted in a correlation between total serum bilirubin and mobile-phone TcB estimated bilirubin with a R 2 = 0.42 and Bland-Altman limits of agreement of +6.4 mg/dL to -7.0 mg/dL. These results indicate that a mobile phone with a modified adapter can be utilized to measure neonatal bilirubin values, thus creating a novel tool for neonatal jaundice screening in low-resource settings., Competing Interests: The authors declare that they have no conflict of interest., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Surface-guided radiotherapy (SGRT) can assist with patient setup by providing a real-time feedback mechanism over the whole patient treatment surface. It also has the potential to reduce the number of close contacts between staff and the patient, which is advocated for infection control during the COVID-19 pandemic. Residual translations and rotations (post-CBCT) were acquired following a conventional setup protocol (using permanent marks and lasers) and an SGRT setup protocol. The SGRT protocol resulted in one of the two therapeutic radiographers not having any close contact (<2m) with a patient during setup. Data from 702 imaging sessions showed similar setup accuracy with either protocol, fewer large translations and fewer repeat setup occurrences using the SGRT protocol. The potential of SGRT for infection control should be recognised alongside other benefits., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)

Rationale: Most contemporary cancer therapeutic paradigms involve initial imaging as a treatment roadmap, followed by the active engagement of surgical operations. Current approved intraoperative contrast agents exemplified by indocyanine green (ICG) have a few drawbacks including the inability of pre-surgical localization. Alternative near-infrared (NIR) dyes including IRDye800cw are being explored in advanced clinical trials but often encounter low chemical yields and complex purifications owing to the asymmetric synthesis. A single contrast agent with ease of synthesis that works in multiple cancer types and simultaneously allows presurgical imaging, intraoperative deep-tissue three-dimensional visualization, and high-speed microscopic visualization of tumor margins via spatiotemporally complementary modalities would be beneficial. Methods: Due to the lack of commercial availability and the absence of detailed synthesis and characterization, we proposed a facile and scalable synthesis pathway for the symmetric NIR water-soluble heptamethine sulfoindocyanine IRDye78. The synthesis can be accomplished in four steps from commercially-available building blocks. Its symmetric resonant structure avoided asymmetric synthesis problems while still preserving the benefits of analogous IRDye800cw with commensurable optical properties. Next, we introduced a low-molecular-weight protein alpha-lactalbumin (α-LA) as the carrier that effectively modulates the hepatic clearance of IRDye78 into the preferred renal excretion pathway. We further implemented 89 Zr radiolabeling onto the protein scaffold for positron emission tomography (PET). The multimodal imaging capability of the fluorophore-protein complex was validated in breast cancer and glioblastoma. Results: The scalable synthesis resulted in high chemical yields, typically 95% yield in the final step of the chloro dye. Chemical structures of intermediates and the final fluorophore were confirmed. Asymmetric IRDye78 exhibited comparable optical features as symmetric IRDye800cw. Its well-balanced quantum yield affords concurrent dual fluorescence and optoacoustic contrast without self-quenching nor concentration-dependent absorption. The NHS ester functionality modulates efficient covalent coupling to reactive side-chain amines to the protein carrier, along with desferrioxamine (DFO) for stable radiolabeling of 89 Zr. The fluorophore-protein complex advantageously shifted the biodistribution and can be effectively cleared through the urinary pathway. The agent accumulates in tumors and enables triple-modal visualization in mouse xenograft models of both breast and brain cancers. Conclusion: This study described in detail a generalized strategic modulation of clearance routes towards the favorable renal clearance, via the introduction of α-LA. IRDye78 as a feasible alternative of IRDye800cw currently in clinical phases was proposed with a facile synthesis and fully characterized for the first time. This fluorophore-protein complex with stable radiolabeling should have great potential for clinical translation where it could enable an elegant workflow from preoperative planning to intraoperative deep tissue and high-resolution image-guided resection., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Seismology records the presence of various heterogeneities throughout the lower mantle 1,2 , but the origins of these signals-whether thermal or chemical-remain uncertain, and therefore much of the information that they hold about the nature of the deep Earth is obscured. Accurate interpretation of observed seismic velocities requires knowledge of the seismic properties of all of Earth's possible mineral components. Calcium silicate (CaSiO 3 ) perovskite is believed to be the third most abundant mineral throughout the lower mantle. Here we simultaneously measure the crystal structure and the shear-wave and compressional-wave velocities of samples of CaSiO 3 perovskite, and provide direct constraints on the adiabatic bulk and shear moduli of this material. We observe that incorporation of titanium into CaSiO 3 perovskite stabilizes the tetragonal structure at higher temperatures, and that the material's shear modulus is substantially lower than is predicted by computations 3-5 or thermodynamic datasets 6 . When combined with literature data and extrapolated, our results suggest that subducted oceanic crust will be visible as low-seismic-velocity anomalies throughout the lower mantle. In particular, we show that large low-shear-velocity provinces (LLSVPs) are consistent with moderate enrichment of recycled oceanic crust, and mid-mantle discontinuities can be explained by a tetragonal-cubic phase transition in Ti-bearing CaSiO 3 perovskite.

Hybrid genotypes have been repeatedly described among natural isolates of Leishmania, and the recovery of experimental hybrids from sand flies co-infected with different strains or species of Leishmania has formally demonstrated that members of the genus possess the machinery for genetic exchange. As neither gamete stages nor cell fusion events have been directly observed during parasite development in the vector, we have relied on a classical genetic analysis to determine if Leishmania has a true sexual cycle. Here, we used whole genome sequencing to follow the chromosomal inheritance patterns of experimental hybrids generated within and between different strains of L. major and L. infantum. We also generated and sequenced the first experimental hybrids in L. tropica. We found that in each case the parental somy and allele contributions matched the inheritance patterns expected under meiosis 97-99% of the time. The hybrids were equivalent to F1 progeny, heterozygous throughout most of the genome for the markers that were homozygous and different between the parents. Rare, non-Mendelian patterns of chromosomal inheritance were observed, including a gain or loss of somy, and loss of heterozygosity, that likely arose during meiosis or during mitotic divisions of the progeny clones in the fly or culture. While the interspecies hybrids appeared to be sterile, the intraspecies hybrids were able to produce backcross and outcross progeny. Analysis of 5 backcross and outcross progeny clones generated from an L. major F1 hybrid, as well as 17 progeny clones generated from backcrosses involving a natural hybrid of L. tropica, revealed genome wide patterns of recombination, demonstrating that classical crossing over occurs at meiosis, and allowed us to construct the first physical and genetic maps in Leishmania. Altogether, the findings provide strong evidence for meiosis-like sexual recombination in Leishmania, presenting clear opportunities for forward genetic analysis and positional cloning of important genes., Competing Interests: The authors have declared that no competing interests exist.

Genetic exchange between Leishmania major strains during their development in the sand fly vector has been experimentally shown. To investigate the possibility of genetic exchange between different Leishmania species, a cutaneous strain of L. major and a visceral strain of Leishmania infantum, each bearing a different drug-resistant marker, were used to coinfect Lutzomyia longipalpis sand flies. Eleven double-drug-resistant progeny clones, each the product of an independent mating event, were generated and submitted to genotype and phenotype analyses. The analysis of multiple allelic markers across the genome suggested that each progeny clone inherited at least one full set of chromosomes from each parent, with loss of heterozygosity at some loci, and uniparental retention of maxicircle kinetoplast DNA. Hybrids with DNA contents of approximately 2n, 3n, and 4n were observed. In vivo studies revealed clear differences in the ability of the hybrids to produce pathology in the skin or to disseminate to and grow in the viscera, suggesting polymorphisms and differential inheritance of the gene(s) controlling these traits. The studies, to our knowledge, represent the first experimental confirmation of cross-species mating in Leishmania, opening the way toward genetic linkage analysis of important traits and providing strong evidence that genetic exchange is responsible for the generation of the mixed-species genotypes observed in natural populations.

Background: Infantile colic is a common disorder, affecting around one in six families, and in 2001 was reported to cost the UK National Health Service in excess of £65 million per year (Morris 2001). Although it usually remits by six months of age, there is some evidence of longer-term sequelae for both children and parents.Manipulative therapies, such as chiropractic and osteopathy, have been suggested as interventions to reduce the severity of symptoms., Objectives: To evaluate the results of studies designed to address efficacy or effectiveness of manipulative therapies (specifically, chiropractic, osteopathy and cranial manipulation) for infantile colic in infants less than six months of age., Search Methods: We searched following databases: CENTRAL (2012, Issue 4), MEDLINE (1948 to April Week 3 2012), EMBASE (1980 to 2012 Week 17), CINAHL (1938 to April 2012), PsycINFO (1806 to April 2012), Science Citation Index (1970 to April 2012), Social Science Citation Index (1970 to April 2012), Conference Proceedings Citation Index - Science (1990 to April 2012) and Conference Proceedings Citation Index - Social Science & Humanities (1970 to April 2012). We also searched all available years of LILACS, PEDro, ZETOC, WorldCat, TROVE, DART-Europe, ClinicalTrials.gov and ICTRP (May 2012), and contacted over 90 chiropractic and osteopathic institutions around the world. In addition, we searched CentreWatch, NRR Archive and UKCRN in December 2010., Selection Criteria: Randomised trials evaluating the effect of chiropractic, osteopathy or cranial osteopathy alone or in conjunction with other interventions for the treatment of infantile colic., Data Collection and Analysis: In pairs, five of the review authors (a) assessed the eligibility of studies against the inclusion criteria, (b) extracted data from the included studies and (c) assessed the risk of bias for all included studies. Each article or study was assessed independently by two review authors. One review author entered the data into Review Manager software and the team's statistician (PP) reviewed the chosen analytical settings., Main Results: We identified six studies for inclusion in our review, representing a total of 325 infants. There were three further studies that we could not find information about and we identified three other ongoing studies. Of the six included studies, five were suggestive of a beneficial effect and one found no evidence that manipulative therapies had any beneficial effect on the natural course of infantile colic. Tests for heterogeneity imply that there may be some underlying difference between this study and the other five.Five studies measured daily hours of crying and these data were combined, suggesting that manipulative therapies had a significant effect on infant colic - reducing average crying time by one hour and 12 minutes per day (mean difference (MD) -1.20; 95% confidence interval (CI) -1.89 to -0.51). This conclusion is sustained even when considering only studies with a low risk of selection bias (sequence generation and allocation concealment) (MD -1.24; 95% CI -2.16 to -0.33); those with a low risk of attrition bias (MD -1.95; 95% CI -2.96 to -0.94), or only those studies that have been published in the peer-reviewed literature (MD -1.01; 95% CI -1.78 to -0.24). However, when combining only those studies with a low risk of performance bias (parental 'blinding'), the improvement in daily crying hours was not statistically significant (MD -0.57; 95% CI -2.24 to 1.09).One study considered whether the reduction in crying time was clinically significant. This found that a greater proportion of parents of infants receiving a manipulative therapy reported clinically significant improvements than did parents of those receiving no treatment (reduction in crying to less than two hours: odds ratio (OR) 6.33; 95% CI 1.54 to 26.00; more than 30% reduction in crying: OR 3.70; 95% CI 1.15 to 11.86).Analysis of data from three studies that measured 'full recovery' from colic as reported by parents found that manipulative therapies did not result in significantly higher proportions of parents reporting recovery (OR 11.12; 95% CI 0.46 to 267.52).One study measured infant sleeping time and found manipulative therapy resulted in statistically significant improvement (MD 1.17; 95% CI 0.22 to 2.12).The quality of the studies was variable. There was a generally low risk of selection bias but only two of the six studies were evaluated as being at low risk of performance bias, three at low risk of detection bias and one at low risk of attrition bias.One of the studies recorded adverse events and none were encountered. However, with only a sample of 325 infants, we have too few data to reach any definitive conclusions about safety., Authors' Conclusions: The studies included in this meta-analysis were generally small and methodologically prone to bias, which makes it impossible to arrive at a definitive conclusion about the effectiveness of manipulative therapies for infantile colic.The majority of the included trials appeared to indicate that the parents of infants receiving manipulative therapies reported fewer hours crying per day than parents whose infants did not, based on contemporaneous crying diaries, and this difference was statistically significant. The trials also indicate that a greater proportion of those parents reported improvements that were clinically significant. However, most studies had a high risk of performance bias due to the fact that the assessors (parents) were not blind to who had received the intervention. When combining only those trials with a low risk of such performance bias, the results did not reach statistical significance. Further research is required where those assessing the treatment outcomes do not know whether or not the infant has received a manipulative therapy.There are inadequate data to reach any definitive conclusions about the safety of these interventions.

Background: Primary endovascular reconstruction with flow diversion represents a fundamental paradigm shift in the technique of endovascular aneurysm treatment. Unlike coil embolization, often there remains residual post-procedural filling within the aneurysm with flow diverters, the curative reconstruction presumably occurring over a period of weeks. Thus, conventional grading scales for post-procedural aneurysm occlusion and recanalization are inadequate. The aim of this paper is to propose a new angiographic grading scale that addresses this fundamentally new treatment option., Method: A five-point grading scale describes the location of residual flow within the aneurysm in the venous phase [grade 1: patent aneurysm with diffuse inflow; grade 2: residual filling of the aneurysm dome (saccular) or wall (fusiform); grade 3: only residual neck (saccular) or only intra-aneurysmal filling with former boundaries covered (fusiform); grade 4: complete occlusion]., Findings: Grade 0 represents any aneurysm, regardless of occlusion rate with early phase, coherent inflow jet. Intra-aneurysmal flow stagnation is categorized into: (a) none, (b) capillary phase, and (c) venous phase. Prevailing parent vessel hemodynamics with in-stent stenosis (ISS) are divided into none (ISS0), mild (ISS1), moderate (ISS2), severe (ISS3), and total (ISS4) occlusion. The proposed grading scales allow assessment of the hemodynamic consequences of stent placement on endosaccular in-flow, stasis, and location of stasis as well as parent vessel hemodynamics., Conclusions: Further studies need to show the applicability and possible predictive value of this new grading scale on the efficacy of the stent in promoting intra-aneurysmal flow stagnation, thus creating the potential to harmonize the results of future papers. This may help to optimize treatment and future device design.

We demonstrate the hohlraum radiation temperature and symmetry required for ignition-scale inertial confinement fusion capsule implosions. Cryogenic gas-filled hohlraums with 2.2 mm-diameter capsules are heated with unprecedented laser energies of 1.2 MJ delivered by 192 ultraviolet laser beams on the National Ignition Facility. Laser backscatter measurements show that these hohlraums absorb 87% to 91% of the incident laser power resulting in peak radiation temperatures of T(RAD)=300 eV and a symmetric implosion to a 100 μm diameter hot core., (© 2011 American Physical Society)

During 2007, a large-scale controlled, multicentre, blinded and randomised field study was conducted in Scotland, England and France to assess the efficacy and safety of monepantel, the first molecule to be developed from the recently discovered amino-acetonitrile derivatives class of anthelmintics, in sheep. Monepantel was administered orally, at a minimum dose of 2.5 mg/kg bodyweight, for the control of gastrointestinal nematodes in sheep maintained at pasture in a range of commercial production systems. Efficacy was measured by faecal egg count (FEC) reduction tests seven days after treatment and was demonstrated to be over 98 per cent against mixed-genus infections. The reduction in FEC of monepantel-treated sheep was statistically significantly greater than in untreated control sheep (P<0.0001). The efficacy of monepantel against mixed-genus natural field infections of the major gastrointestinal nematodes was in agreement with similar studies conducted in Australia and New Zealand. There were no treatment-related adverse events during the study, which included the use of a range of concomitant treatments.

Post-perovskite MgSiO(3) is believed to be present in the D'' region of the Earth's lowermost mantle. Its existence has been used to explain a number of seismic observations, such as the D'' reflector and the high degree of seismic anisotropy within the D'' layer. Ionic diffusion in post-perovskite controls its viscosity, which in turn controls the thermal and chemical coupling between the core and the mantle, the development of plumes and the stability of deep chemical reservoirs. Here we report the use of first-principles methods to calculate absolute diffusion rates in post-perovskite under the conditions found in the Earth's lower mantle. We find that the diffusion of Mg(2+) and Si(4+) in post-perovskite is extremely anisotropic, with almost eight orders of magnitude difference between the fast and slow directions. If post-perovskite in the D'' layer shows significant lattice-preferred orientation, the fast diffusion direction will render post-perovskite up to four orders of magnitude weaker than perovskite. The presence of weak post-perovskite strongly increases the heat flux across the core-mantle boundary and alters the geotherm. It also provides an explanation for laterally varying viscosity in the lowermost mantle, as required by long-period geoid models. Moreover, the behaviour of very weak post-perovskite can reconcile seismic observation of a D'' reflector with recent experiments showing that the width of the perovskite-to-post-perovskite transition is too wide to cause sharp reflectors. We suggest that the observed sharp D'' reflector is caused by a rapid change in seismic anisotropy. Once sufficient perovskite has transformed into post-perovskite, post-perovskite becomes interconnected and strain is partitioned into this weaker phase. At this point, the weaker post-perovskite will start to deform rapidly, thereby developing a strong crystallographic texture. We show that the expected seismic contrast between the deformed perovskite-plus-post-perovskite assemblage and the overlying isotropic perovskite-plus-post-perovskite assemblage is consistent with seismic observations.

Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirusbattus, Nematodirusfilicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95<100%) efficacy of monepantel when administered orally to sheep at 2.5mg/kg for most species tested. Efficacy levels against N. spathiger and O. venulosum were variable and failed to meet the required regulatory standard (> or =90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed.

Potent and selective ligands of the alpha7 nicotinic acetylcholine receptor are required to understand the pharmacological effect of alpha7 activation. A common cross-reactivity occurs with serotonergic 5-HT3 receptors with which alpha7 receptors have a high sequence homology. We demonstrate that certain quinuclidine 3-biaryl carboxamides are high affinity alpha7 ligands with an excellent binding selectivity over 5-HT3 receptors.

The binding of the norepinephrine transporter radioligand, (S,S)-[18F]FMeNER-D2, to human brain post-mortem was examined in vitro by whole hemisphere autoradiography. The rank order for the density of labelling was: locus coeruleus>>cortex approximately cerebellum approximately thalamus>caudate approximately putamen. The NET-selectivity of binding was confirmed by co-incubation with desipramine. The dual NET/SERT inhibitor duloxetine also inhibited specific binding, whereas PE2I or citalopram had no evident effect.

The area of bowel care in the intensive care unit (ICU) is often overlooked in the holistic care of the critically ill individual. With the primary concern of optimising patients to preserve life the problem of bowel care has been given less priority. The guidelines included within this service improvement paper offer a simple approach to bowel care management with the use of an algorithm and visual display score to be used in conjunction with the algorithm. This was developed in the intensive care unit of the Royal Free Hospital, London and is presently in use.

(S,S)-2-(alpha-(2-Fluoromethoxyphenoxy)benzyl)morpholine ((S,S)-FMeNER) was found to be a selective high-affinity ligand for the norepinephrine transporter (NET). (S,S)-FMeNER) was labeled with fluorine-18 (t1/2 = 109.8 min) by O-fluoromethylation of desfluoromethoxy-(S,S)-FMeNER with [18F]bromofluoromethane. An analog, di-deuterated in the fluoromethoxy group ((S,S)-FMeNER-D2), was similarly labeled with di-deutero-[18F]bromofluoromethane. These two new radioligands were obtained in radiochemical purities greater than 98% and with specific radioactivities ranging from 111-185 GBq/micromol at the end of synthesis (75 min). After intravenous injection of (S,S)-[18F]FMeNER into cynomolgus monkey, PET examination with the head in the field of view revealed skull-bound radioactivity, contaminating images of the brain, and indicated fast defluorination of the radioligand. Defluorination was much reduced in similar PET experiments with (S,S)-[18F]FMeNER-D2. Ratios of radioactivity in the lower brainstem, mesencephalon, thalamus, and temporal cortex to striatum obtained with (S,S)-[18F]FMeNER-D2 at 160 min after i.v. injection were 1.5, 1.6, 1.3, and 1.5, respectively. In another PET experiment, pretreatment of the monkey with the selective NET inhibitor, desipramine, decreased the radioactivity ratios in all examined regions to near unity (e.g., to a ratio of 1.03 in mesencephalon). Labeled metabolites of (S,S)-[18F]FMeNER-D2 or (S,S)-[18F]FMeNER found in plasma were all more polar than the parent radioligand. In vitro autoradiography of (S,S)-[18F]FMeNER-D2 on post-mortem human brain cryosections furthermore showed specific binding to NET in the locus coeruleus and thalamus. (S,S)-[18F]FMeNER-D2 is the first useful radiofluorinated ligand for imaging brain NET in monkey in vivo and is superior to (S,S)-[11C]MeNER because a specific binding peak equilibrium is obtained during the PET experiment at a lower noise level., (Copyright 2004 Wiley-Liss, Inc.)

Recent evidence indicates that adenosine A2A receptors modulate the activity of striatal neurons, and that antagonists of this receptor may have actions in various animal models related to motor function. Four experiments were conducted to study the effects of systemic injections of the adenosine A2A antagonist KF17837 on the behavioral effects produced by repeated administration of the dopamine (DA) antagonist haloperidol. In the first two experiments, it was shown that repeated 0.5 mg/kg haloperidol severely suppressed open-field locomotor activity, and that KF17837 (0.0-20.0 mg/kg) did not significantly increase open-field locomotor activity. The third experiment demonstrated that injections of KF17837 (0.0-20.0 mg/kg) completely reversed the suppression of locomotion induced by haloperidol, and also increased rearing behavior in haloperidol-treated rats. Previous research has reported that haloperidol induces tremulous jaw movements that have many of the characteristics of parkinsonian tremor. The fourth experiment demonstrated that i.p. injections of KF17837 (0.0-20.0 mg/kg) also suppressed haloperidol-induced tremulous jaw movements. Taken together, the results of these experiments indicate that adenosine A2A antagonism can reverse the locomotor suppression and tremulous movements induced by DA antagonism. This profile of activity is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in an antiparkinsonian effect in animal models.

The boundary between the Earth's metallic core and its silicate mantle is characterized by strong lateral heterogeneity and sharp changes in density, seismic wave velocities, electrical conductivity and chemical composition. To investigate the composition and properties of the lowermost mantle, an understanding of the chemical reactions that take place between liquid iron and the complex Mg-Fe-Si-Al-oxides of the Earth's lower mantle is first required. Here we present a study of the interaction between iron and silica (SiO2) in electrically and laser-heated diamond anvil cells. In a multianvil apparatus at pressures up to 140 GPa and temperatures over 3,800 K we simulate conditions down to the core-mantle boundary. At high temperature and pressures below 40 GPa, iron and silica react to form iron oxide and an iron-silicon alloy, with up to 5 wt% silicon. At pressures of 85-140 GPa, however, iron and SiO2 do not react and iron-silicon alloys dissociate into almost pure iron and a CsCl-structured (B2) FeSi compound. Our experiments suggest that a metallic silicon-rich B2 phase, produced at the core-mantle boundary (owing to reactions between iron and silicate), could accumulate at the boundary between the mantle and core and explain the anomalously high electrical conductivity of this region.

The sequencing of Leishmania major Friedlin chromosome 1 (Chr1), Chr3, and Chr4 has been completed. and several other chromosomes are well underway. The complete genome sequence should be available by 2003. Over 1,000 full-length new genes have been identified, with the majority (approximately 75%) having unknown function. Many of these may be Leishmania (or kinetoplastid) specific. Most interestingly, the genes are organized into large (> 100-500 kb) polycistronic clusters of adjacent genes on the same DNA strand. Chr1 contains two such clusters organized in a "divergent" manner, i.e., the mRNAs for the two sets of genes are both transcribed towards the telomeres. Nuclear run-on analysis suggests that transcription is initiated in both directions within the "divergent" region. Chr3 and Chr4 contain two "convergent" clusters, with a single "divergent" gene at one telomere of Chr3. Sequence analysis of several genes from the LD1 region of Chr35 indicates a high degree of sequence conservation between L. major and L. donovani/L. infantum within protein-coding open reading frames (ORFs), with a lower degree of conservation within the non-coding regions. Immunization of mice with recombinant antigen from two of these genes, BTI (formerly ORFG) and ORFF, results in significant reduction in parasite burden following Leishmania challenge. Recombinant ORFF antigen shows promise as a serodiagnostic. We have also developed a tetracycline-regulated promoter system, which allows us to modulate gene expression in Leishmania.

Fat mass, adipocyte size and metabolic responsiveness, and preadipocyte differentiation decrease between middle and old age. We show that expression of CCAAT/enhancer binding protein (C/EBP)-alpha, a key regulator of adipogenesis and fat cell function, declined substantially with aging in differentiating preadipocytes cultured under identical conditions from rats of various ages. Overexpression of C/EBP alpha in preadipocytes cultured from old rats restored capacity to differentiate into fat cells, indicating that downstream differentiation-dependent genes maintain responsiveness to regulators of adipogenesis. C/EBP alpha-expression also decreased with age in fat tissue from three different depots and in isolated fat cells. The overall level of C/EBP beta, which modulates C/EBP alpha-expression, did not change with age, but the truncated, dominant-negative C/EBP beta-liver inhibitory protein (LIP) isoform increased in cultured preadipocytes and isolated fat cells. Overexpression of C/EBP beta-LIP in preadipocytes from young rats impaired adipogenesis. C/EBP delta, which acts with full-length C/EBP beta to enhance adipogenesis, decreased with age. Thus processes intrinsic to adipose cells involving changes in C/EBP family members contribute to impaired adipogenesis and altered fat tissue function with aging. These effects are potentially reversible.

Rates of cation diffusion (magnesium, iron, and nickel) have been determined in olivine and its high-pressure polymorph, wadsleyite, at 9 to 15 gigapascals and 1100 degrees to 1400 degreesC for compositions that are relevant to Earth's mantle. Diffusion in olivine becomes strongly dependent on composition at high pressure. In wadsleyite, diffusion is one to two orders of magnitude faster than in olivine, depending on temperature. Homogenization of mantle heterogeneities (chemical mixing) and mineral transformations involving a magnesium-iron exchange will therefore occur considerably faster in the transition zone than at depths of less than 410 kilometers.

Objective: To review recent findings about changes with age in the replication and differentiation of preadipocytes, the progenitor cells in fat tissue that are capable of differentiating into fat cells, and to examine possible links between these alterations and age-related changes in fat tissue function., Design: A survey and analysis of recent literature concerning changes in preadipocyte and fat cell function with age., Conclusions: Intrinsic aging changes in fat cells and preadipocytes as well as in factors extrinsic to fat tissue (such as food intake and absorption and hormonal status) contribute to age-related alterations in fat tissue function and cellularity. Changes with age in preadipocyte number, replicative potential, and capacity for differentiation, which may be linked to aging changes in fat cell size, number, and function, have been identified. The decline in preadipocyte capacity for differentiation and the associated decline in fat cell lipogenic capacity may be particularly important in contributing to the decrease in fat mass and alterations in fat tissue function that occur between middle- and old age. These declines result from blunting of the changes in gene expression that occur during preadipocyte differentiation and may, in turn, be related to altered regulation of particular transcription factors that control the preadipocyte differentiation program and maintenance of fat cell function.

The purpose of the present study was to determine the usefulness of the monoclonal antibodies 7-D-4 and 3-B-3 as biomarkers of severity of naturally occurring osteoarthritis in the knee joints of adult cynomolgus macaques. The antibodies were used to immunolocate chondroitin sulfate proteoglycan epitopes in articular cartilage or synovial fluid from knee joints with a range in severity of osteoarthritis. The joints were examined radiographically, grossly, microradiographically, and histologically to characterize the severity of disease, and the results of three different methods of proteoglycan analysis (immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analysis) were compared. Subjectively, the degree of positive immunostaining for 7-D-4 was minimal in normal sites and increased as damage to articular cartilage increased. The scores for 7-D-4 immunostaining in the medial tibial plateau (the site most severely involved in this model) were correlated significantly with severity of damage to articular cartilage (p < 0.05, r2 = 0.50), thus supporting the subjective observations. The ratio of 7-D-4 to sulfated glycosaminoglycans in synovial fluid also was correlated with the score for 7-D-4 immunostaining in the medial tibial plateau (p < 0.05, r2 = 0.54) and with the score for 3-B-3 immunostaining in the medial femoral condyle (p < 0.05, r2 = 0.65). There were no significant correlations among scores for 3-B-3 immunostaining, severity scores, and the ratios of 3-B-3 to sulfated glycosaminoglycans in the synovial fluid. By Western blot analysis, both epitopes were sensitive markers of early cartilage damage in young adult monkeys but were less sensitive in older monkeys. This work provides evidence that measurement of the epitope recognized by 7-D-4 in synovial fluid or, by immunohistochemical or Western blot methods, in articular cartilage has potential use as a marker of severity of naturally occurring osteoarthritis.

Objective: The study compared the effects of social skills training and social milieu treatment on symptoms of schizophrenia, particularly on negative symptoms., Methods: Thirty-three patients aged 18 to 55 years with a diagnosis of schizophrenia were randomly assigned to a nine-week program of social skills training or social milieu treatment. Patients were assessed at three-, six-, and nine-week intervals during treatment and at follow-up using the Positive and Negative Syndrome Scale (PANSS), which measured both positive and negative symptoms of schizophrenia and general psychopathology., Results: Fifteen patients completed social skills training, and 13 completed social milieu treatment. Comparison of PANSS scores at different assessment times showed that both treatments were effective in reducing symptoms, but social skills training appeared to be more effective in reducing negative symptoms. No differences were found between treatment groups in relapse rates or in symptom measures at three-month follow-up. However, six-month follow-up data available only for the social skills training group showed that improvement in negative symptoms had begun to decline., Conclusions: Psychosocial approaches are a necessary component in the treatment of patients with schizophrenia, and social skills training appears to be particularly helpful. The gradual decline in improvement in negative symptoms at six-month follow-up suggests the need for more extended treatment.

A uterine pessary containing penicillin, streptomycin, formosulphathiazole and ethinyloestradiol, was assessed for its efficacy in reducing the frequency and severity of uterine infections in cows after parturition. Fifteen pluriparous Holstein Friesian cows had pessaries inserted into the uterus within 24 hours after calving. Compared with 14 similar untreated cows there were significant reductions in the number infected by Actinomyces pyogenes and in the number exhibiting abnormal uterine discharges.

A computed tomographic image transfer system ('Image Link') was used to link scanners within the Oxford region, UK, to the regional neurosurgical service. 100 consecutive neurosurgical referrals were examined by this system; 43% of the emergency referrals did not require transfer, 31% were transferred electively, and 26% urgently. Most of the patients defined as potentially hazardous for transfer (10/11) did not require neurosurgical intervention. The delay by the use of the system was negligible and early detection of intracranial haematoma contributed to good outcome in some head injured patients. Overall, 3,170 miles of ambulance journey were avoided. Use of image link has led to substantial improvements in management of neurosurgical emergency referrals, cost-effectiveness of neurosurgical and ambulance facilities, and interhospital communication between doctors.

Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.

Forty lactating Holstein cows were fed 0, 5.9, 11.7, or 17.4% processed poultry excreta in total mixed rations. The effect of treatment was evaluated on feed intake, BW, milk yield, and composition. Processes poultry excreta appeared to be well accepted by cows even when included in rations at 17.4% of total DM. Mean DM intake averaged 19.3, 19.7, 19.5, and 19.7 kg/d for cows fed 0, 5.9, 11.7, and 17.4% processed poultry excreta, respectively. Body weight change averaged 2.0, 1.7, -1.7, and 1.4 kg/wk from 90 to 180 d of lactation for cows fed from 0 to 17.4% processed poultry excreta, respectively. Fat-corrected milk (4%) yield was similar among treatment groups, averaging 24.2, 26.1, 24.6, and 25.1 kg/d for cows fed 0, 5.9, 11.7, and 17.4% processed poultry excreta. No differences were found for milk and fat yields of percentage fat among treatment means. No off flavors in milk could be attributed to processed poultry excreta added to feed. Processed poultry excreta fed up to 17.4% of total mixed rations supported both adequate feed intake and high milk yields of mid-lactation cows.

Gene fusions between the mouse mammary tumor virus long terminal repeat and the E. coli lacZ gene have been shown to exhibit hormone dependent expression of beta-galactosidase activity. These constructions were used in transient expression experiments to assess the effects of specific modifications introduced into the region upstream of the transcription initiation site. 5' deletions demonstrate that sequences sufficient for wild-type promoter function are contained downstream of residue -64 relative to the initiation site. Other deletions define a region of approximately 80 base pairs between -220 and -140 which contains sequences essential for hormonal control. Between this control region and the promoter lie sequences dispensable for both functions.