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Background Mechanochemical ablation (MOCA) is an alternative method to endovenous thermal ablation (EVTA) for the treatment of superficial venous incompetence that does not require tumescent anaesthesia. The aim of this study was to compare the outcomes from RCTs of MOCA versus EVTA. Methods A search was conducted in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). Meta-analysis inclusion was restricted to RCTs comparing MOCA against EVTA. Outcomes included anatomical occlusion rate, disease-specific quality of life using the Aberdeen Varicose Vein Questionnaire, procedural and postprocedural pain, and rates of venous thromboembolism. Results Four RCTs were included in the meta-analysis comprising 654 patients. The anatomical occlusion rate at 1 year was lower after MOCA than EVTA (risk ratio 0.85, 95 per cent c.i. 0.78 to 0.91; P < 0.001). No significant differences were detected in procedural pain (mean difference −3.25, −14.25 to 7.74; P = 0.560) or postprocedural pain (mean difference −0.63, −2.15 to 0.89; P = 0.420). There were no significant differences in Aberdeen Varicose Vein Questionnaire score at 1 year (mean difference 0.06, −0.50 to 0.62; P = 0.830) or in incidence of venous thromboembolism (risk ratio 0.72, 95 per cent c.i. 0.14 to 3.61; P = 0.690). Conclusion The rate of successful anatomical occlusion after MOCA is significantly lower than that after EVTA, but there is no difference in procedural and postprocedural pain between the two interventions. Long-term data are required to assess the impact of the reduced vein occlusion rate on clinical outcomes such as quality of life and reintervention.

Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents. It can present as a mass at nearly any site in the body, with most common presentations in the head and neck, genitourinary tract and extremities. The optimal diagnostic approach and management of rhabdomyosarcoma require a multidisciplinary team with multimodal treatment, including chemotherapy and local therapy. Survival has improved over the last decades; however, further improvement in management is essential with current 5-year overall survival ranging from 35% to 100%, depending on disease and patient characteristics. In the full patient journey, from diagnosis, staging, management to follow-up after therapy, the paediatric radiologist and nuclear physician are essential members of the multidisciplinary team. Recently, guidelines of the European paediatric Soft tissue sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR), in an ongoing collaboration with the International Soft-Tissue Sarcoma Database Consortium, provided guidance for high-quality imaging. In this educational paper, given as a lecture during the 2022 postgraduate ESPR course, the multi-disciplinary team of our national paediatric oncology centre presents the journey of two patients with rhabdomyosarcoma and discusses the impact on and considerations for the clinical (paediatric) radiologist and nuclear physician. The key learning points of the guidelines and their implementation in clinical practice are highlighted and up-to-date insights provided for all aspects from clinical suspicion of rhabdomyosarcoma and its differential diagnosis, to biopsy, staging, risk stratification, treatment response assessment and follow-up.

We examined whether the difficulties of patients with somatoform disorders (SFDs) in integrating medical reassurance can be altered by preventing patients from devaluing reassuring information through defensive cognitive strategies.Patients with SFD (As evident on all outcome variables, patients with SFD had more difficulty integrating medical reassurance than depressed and healthy people. Within the SFD sample, participants from the experimental condition blocking the devaluation of medical reassurance rated the likelihood of an undetected serious disease to be significantly lower than the other two conditions. They also reported less emotional concern and a lower desire to seek the opinion of another doctor.By comparing patients with SFD to both a healthy and a clinical control group, the current study suggests that the difficulty in processing reassuring medical information is a specific psychopathological feature of SFD. Furthermore, our results suggest that the integration of medical reassurance can be improved by preventing patients from devaluing reassuring information through dismissive cognitive strategies. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

People with type 2 diabetes mellitus (T2DM) have a higher risk of developing chronic liver disease (CLD) and its complications. T2DM, obesity, and insulin resistance are all strongly associated with nonalcoholic fatty liver disease (NAFLD). Conversely, people suffering from cirrhosis have reduced glucose tolerance in approximately 60% of cases, diabetes in 20% of cases, and insulin-mediated glucose clearance is lowered by 50% as compared with those who do not have cirrhosis. An exploratory review was conducted using existing published evidence from clinical studies on dosing and titrations of individual insulin formulations in people with CLD to optimize insulin dosage titration for minimizing hypoglycemia risk. This article discusses current hyperglycemia treatment techniques for patients with CLD as well as the consensus recommendations on insulin use in special populations with T2DM and hepatic impairment. Based on available evidence and expert diabetologists’ recommendations, careful insulin dose titration, customized glycemic targets, and frequent glucose screening are recommended for optimal glycemic management without hypoglycemia in CLD. Long-acting insulin should be avoided or used when short-acting insulin fails to provide adequate glycemic control with raised fasting blood sugar levels. While the patient’s glucose profile is being evaluated, the prandial insulin dose can be lowered by 25% initially. The dose can be titrated based on the patient’s postprandial glycemic expression and whether their food intake meets the Child–Pugh scores A and B categories. Titrating premixed insulins is difficult for patients in class C since their appetite and overall health are constantly compromised and in flux.

The Walker Top Granite (here formally named) is a peraluminous megacrystic granite that occurs in the Cat Square terrane, Inner Piedmont, part of the southern Appalachian Acadian-Neoacadian deformational and metamorphic core. The granite occurs as disconnected concordant to semi-concordant plutons in migmatitic, sillimanite zone rocks of the Brindle Creek thrust sheet. Locally garnet-bearing, the Walker Top Granite contains blocky alkali feldspar megacrysts 1–10 cm long in a groundmass of muscovite-biotite-quartz-plagioclase-alkali feldspar and accessory to trace zircon, titanite, epidote, sillimanite (xenocrysts), and apatite. It varies from granite to granodiorite and contains several xenoliths of biotite gneiss, amphibolite, quartzite, and in one location encloses charnockite (here formally named Vale Charnockite). New sensitive high-resolution ion microprobe U-Pb zircon magmatic crystallization ages obtained from the plutons of the Walker Top Granite are: 407 ± 1 Ma in the Brushy Mountains; 366 ± 2 Ma in the South Mountains; and 358 ± 5 Ma in the Vale–Cat Square area. An age of 366 ± 3 Ma was obtained from the Vale Charnockite at its type locality. Major-, trace-element, and isotopic chemistry indicates that Walker Top is a high-K, peraluminous granite, plotting as volcanic arc or syn-collisional on tectonic discrimination diagrams and suggests that it represents deep-seated anatectic magma with S- to I-type affinity. The alkali calcic, ferroan Vale Charnockite likely formed by deep crustal melting, and similar geochemical and trace-element compositions suggest a similar tectonic origin as Walker Top Granite. The discontinuous nature of the Walker Top Granite plutons precludes it intruded as a volcanic arc. Instead, the peraluminous nature, common xenoliths of surrounding country rock, and geochemical and isotopic signatures suggest it formed by partial melting of Cat Square and Tugaloo terrane rocks. Following emplacement and crystallization, Walker Top plutons were deformed into elliptical to linear shapes—SW-directed sheath folds—enveloped by partially melted, pelitic and quart-zofeldspathic rocks. Collectively, Walker Top and other plutons helped weaken the crust and facilitate lateral crustal flow in a SW-directed, tectonically driven orogenic channel during the Acadian-Neoacadian event. A comparison with the northern Appalachians recognizes a similar temporal magmatic and deformational history during the Acadian and Neoacadian orogenies, although while the Walker Top Granite intruded the lower plate during eastward subduction beneath the peri-Gondwanan Carolina superterrane, the northern Appalachian plutons intruded the upper plate during subduction of the Avalon superterrane westward beneath Laurentia. We hypothesize that a transform fault, located near the southern end of the New York promontory, accommodated oppositely directed lateral plate motion and different subduction polarity between the Carolina and Avalon superterranes during the Acadian and Neoacadian orogenies.

Improving the tailorability of hydrochar synthesis is an effective way to enhance its performance and utilization efficiency. In this study, the growth rate, morphology, and molecular structure of hydrochar were controlled by regulating the pH and temperature of the hydrothermal carbonization process. Growth process analysis indicates that hydrochar has three growth periods: induction, rapid, and stable growth periods. It is mainly controlled by 5-hydroxymethylfurfural (HMF), which is formed by converting glucose and its transformation products. The regulation of acid can significantly shorten the induction period of hydrochar, even under low-temperature conditions (180℃), and increase the growth rate of hydrochar. However, the degree of hydrochar adhesion varies: the lower the temperature, the greater the degree of its adhesion. Molecular structural analysis demonstrates that hydrochar mainly consists of furan structural domains and aromatic clusters, and its surface is rich in oxygen-containing functional groups. The degree at which hydrochar was aromatized was improved by increasing the reaction temperature (160-220℃); whereas the regulation of acid reduced it and increased the content of oxygen-containing functional groups on the hydrochar surface. Based on these results, it is proposed that hydrochar formation has five stages and three growth periods with or without acid regulation.

APW pretreatment of SCB for enhanced sugar production and correlation analysis of pretreated SCB and EHE.

Highly stable CeFeOx thin films that can undergo a reversible fluorite to perovskite phase transition were synthesized.

Truncus arteriosus with interrupted aortic arch (TA-IAA) is a rare congenital heart defect with historically poor outcomes. Contemporary multicenter data are limited.A retrospective cohort study of children who underwent repair of TA-IAA between 2009 and 2016 at 12 tertiary care referral centers within the United States was performed. Major adverse cardiac events (MACE) were defined as postoperative extracorporeal membrane oxygenation, cardiopulmonary resuscitation, or operative mortality. TA-IAA patients were compared with TA patients who underwent repair during the study period from the same institutions.We reviewed 35 patients with TA-IAA. MACE occurred in 12 patients (34%). Improvement over time was observed during the study period with 11 events (92%) occurring in the first half of the study period (P = .03). Factors associated with MACE included moderate or severe truncal valve insufficiency (P.01), concomitant truncal valve repair (P = .04), and longer cardiopulmonary bypass duration (P = .02). In comparison with 216 patients who underwent TA repair, patients with TA-IAA had a higher rate of MACE, but this finding was not statistically significant (34% vs 20%, respectively; P = .07). Additionally no differences between TA-IAA and TA groups were observed for unplanned reoperations (14% vs 22%, respectively; P = .3), hospital length of stay (24 vs 23 days, P = .65), or late deaths (7% vs 7%, P = 1.00).In this contemporary, multicenter cohort the rate of MACE after repair of TA-IAA was high but improved during the study period. Early childhood outcomes of patients with TA-IAA were similar to those with TA.

The discovery and valorization of the unique homogeneous linear catechyl lignin (C-lignin) are systematically summarized.

This study investigated a high-solid diol deep eutectic solvent (DES) pretreatment using a wet substrate as the starting material.

Lignin has great potential as a natural, green, and sustainable broad-spectrum sunscreen active ingredient. However, the coexistence of dark color and sunscreen properties hinders its application in cosmetics. In this study, we focus on the effects of the molecular weight of lignin on tis UV-protecting property and color in order to prepare lignin-based sunscreen with high performance. A prepared sunscreen containing low molecular weight lignin (F5,1000 g/mol) exhibits good UV-protecting property (sun protection factor (SPF) = 7.14) and light color advantages (ΔE = 46.2). Moreover, a strong synergistic effect on UV-protecting property exists between low molecular weight lignin and ethylhexyl methoxycinnamate (EHMC), resulting in high SPF of F5@EHMC-based sunscreen (55.56). Additionally, added TiO

Exercise is one of the only non-pharmacologic remedies known to counteract genetic and chronic diseases by enhancing health and improving life span. Although the many benefits of regular physical activity have been recognized for some time, the intricate and complex signalling system triggered at the onset of exercise have only recently begun to be uncovered. Exercising muscles initiate a coordinated, multisystemic, metabolic rewiring which is communicated to distant organs by various molecular mediators, including extracellular vesicles such as exosomes. The field of exercise research has been expanding beyond the musculoskeletal system, with interest from industry to provide realistic models and exercise mimetics that evoke a whole-body rejuvenation response. This year's 18th International Biochemistry of Exercise conference took place in Toronto, Canada, from May 25th to May 28th, 2022, with more than 400 attendees. Here we provide an overview of the most cutting-edge exercise-related research presented by 66 speakers, focusing on new developments in topics ranging from molecular and cellular mechanisms of exercise adaptations, diabetes, and aging. We also provide descriptions on how manipulation of these signaling pathways provide therapeutic avenues for improving human health and quality of life.

Historically, to minimize risks, living kidney donors have been highly selected and healthy. Operative risks are well-defined, yet concern remains about long-term risks. In the general population, even a mild reduction in glomerular filtration rate (GFR) is associated with cardiovascular disease, chronic kidney disease, and end-stage kidney disease (ESKD). However, reduction in GFR in the general population is due to kidney or systemic disease. Retrospective studies comparing donors with matched general population controls have found no increased donor risk. Prospective studies comparing donors with controls (maximum follow-up, 9 years) have reported that donor GFR is stable or increases slightly, whereas GFR decreases in controls. However, these same studies identified metabolic and vascular donor abnormalities. There are a few retrospective studies comparing donors with controls. Each has limitations in selection of the control group, statistical analyses, and/or length of follow-up. One such study reported increased donor mortality; 2 reported a small increase in absolute risk of ESKD. Risk factors for donor ESKD are similar to those in the general population. Postdonation pregnancies are also associated with increased risk of hypertension and preeclampsia. There is a critical need for long-term follow-up studies comparing donors with controls from the same era, geographic area, and socioeconomic status who are healthy, with normal renal function on the date matching the date of donation, and are matched on demographic characteristics with the donors. These data are needed to optimize donor candidate counseling and informed consent.

To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls.Retrospective clinical cohort study.Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP).There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10).Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls.

Over 35 million Americans have lymphedema. Nonetheless, lymphedema is underdiagnosed and undertreated worldwide. We investigated whether the rates of coverage for imaging and surgical procedures may contribute to the limited care provided for lymphedema.We performed a cross-sectional evaluation of 58 insurers, chosen based on state enrollment and market share. A web-based search or phone call determined whether a publicly available policy on lymphedema-specific imaging, physiological procedures, and excisional procedures was available. Coverage status and corresponding criteria were extracted.Of the two-thirds of insurers who included a policy on imaging, 4% (n = 2) provided coverage and 4% (n = 2) specified coverage only on a case-by-case basis. Forty-eight percent (n = 28) of insurers had a statement of coverage on lymphovenous bypass or vascularized lymph node transfer, in which reimbursement was almost universally denied (96%, n = 26; 93%, n = 26). Liposuction and debulking procedures were included in 25 (43%) and 13 (22%) policies, in which seven (28%) and four (31%) insurers would provide coverage, with over 75% having criteria. Coverage of liposuction was significantly more than for lymphovenous bypass (P .04).Nearly one-half of American insurers do not have a publicly available policy on most imaging, physiological, or excisional procedures, leaving coverage status ambiguous. Reimbursement was uncommon for imaging and physiological procedures, whereas the majority of insurers who did offer coverage for excisional procedures also had multiple criteria to be met. These elements may together be a limiting factor in receiving appropriate care for lymphedema.

Neurodevelopmental disorders (NDDs), including severe paediatric epilepsy, autism and intellectual disabilities are heterogeneous conditions in which clinical genetic testing can often identify a pathogenic variant. For many of them, genetic therapies will be tested in this or the coming years in clinical trials. In contrast to first-generation symptomatic treatments, the new disease-modifying precision medicines require a genetic test-informed diagnosis before a patient can be enrolled in a clinical trial. However, even in 2022, most identified genetic variants in NDD genes are ‘variants of uncertain significance’. To safely enrol patients in precision medicine clinical trials, it is important to increase our knowledge about which regions in NDD-associated proteins can ‘tolerate’ missense variants and which ones are ‘essential’ and will cause a NDD when mutated. In addition, knowledge about functionally indispensable regions in the 3D structure context of proteins can also provide insights into the molecular mechanisms of disease variants. We developed a novel consensus approach that overlays evolutionary, and population based genomic scores to identify 3D essential sites (Essential3D) on protein structures. After extensive benchmarking of AlphaFold predicted and experimentally solved protein structures, we generated the currently largest expert curated protein structure set for 242 NDDs and identified 14 377 Essential3D sites across 189 gene disorders associated proteins. We demonstrate that the consensus annotation of Essential3D sites improves prioritization of disease mutations over single annotations. The identified Essential3D sites were enriched for functional features such as intermembrane regions or active sites and discovered key inter-molecule interactions in protein complexes that were otherwise not annotated. Using the currently largest autism, developmental disorders, and epilepsies exome sequencing studies including >360 000 NDD patients and population controls, we found that missense variants at Essential3D sites are 8-fold enriched in patients. In summary, we developed a comprehensive protein structure set for 242 NDDs and identified 14 377 Essential3D sites in these. All data are available at https://es-ndd.broadinstitute.org for interactive visual inspection to enhance variant interpretation and development of mechanistic hypotheses for 242 NDDs genes. The provided resources will enhance clinical variant interpretation and in silico drug target development for NDD-associated genes and encoded proteins.

The lifecycle of black carbon (BC)-containing particles from biomass burns is examined using aircraft and surface observations of the BC mixing state for plume ages from ∼15 min to 10 days. Because BC is nonvolatile and chemically inert, changes in the mixing state of BC-containing particles are driven solely by changes in particle coating, which is mainly secondary organic aerosol (SOA). The coating mass initially increases rapidly (

To determine the level of interest in standardization of design for fracture fixation implants within the orthopaedic trauma community.A survey regarding implant removal concerns and implant design preferences was electronically distributed to members of Orthopaedic Trauma Association (OTA).Three hundred thirty respondents participated in the survey (response rate of 19%) Only 2.4% of respondents indicated a consistent ability to identify the implant vendor and/or manufacturer of retained implants in the preoperative planning phase of care;gt;75% of respondents reported investing a minimum of an additional 30 minutes to their operative times to remove screw(s) to successfully extract a plate. More than 80% of respondents reported multiple occurrences requiring modification of their surgical plans because of implants that could not be removed, preventing the completion of the planned procedure. The majority of respondents expressed interest in the adoption of standardized locking head screws for mini, small, and large screw sizes sets (63.5%); 84.8% of respondents desire standardization of screw head and driver sizes across the industry. Also, 83.6% of respondents expressed interest in the adoption of a standardized locking screw head for each cannulated screw, regardless of manufacturer.Members of the orthopaedic community, as represented in the membership of the OTA, are interested in the adoption of universal standards in implant design. Establishing standard screw heads and drivers will optimize the delivery of operative care.

Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD.We recruited children with IBD, ages 5-17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization.Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 μg/mL (SD 67) and a median of 22 μg/mL (interquartile range 12-38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant.Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

As North America collided with Africa to form Pangea during the Alleghanian orogeny, crystalline and sedimentary rocks in the southeastern United States were thrust forelandward along the Appalachian décollement. We examined Ps receiver functions to better constrain the kinematics of this prominent subsurface structure. From Southeastern Suture of the Appalachian Margin Experiment (SESAME) and other EarthScope stations on the Blue Ridge–Piedmont crystalline megathrust, we find large arrivals from a 5–10-km-deep converter. We argue that a strong contrast in dipping anisotropic foliation occurs at the subhorizontal Appalachian décollement, and propose that such a geometry may be typical for décollement structures. Conversion polarity flips can be explained by an east-dipping foliation, but this orientation is at odds with the overlying northeast-trending surface tectonic grain. We suggest that prior to late Alleghanian northwest-directed head-on collision, the Appalachian décollement accommodated early Alleghanian west-vergence, independent of the overlying Blue Ridge–Piedmont structural inheritance. The geophysical expression of dipping anisotropic foliation provides a powerful tool for investigating subsurface kinematics, especially where they are obscured by overlying fabric, to disentangle the tectonic complexities that embody oblique collisional orogens.

To report a case of severe ovarian hyperstimulation syndrome (OHSS) persisting into the late second trimester of a singleton pregnancy.Case report.Academic tertiary care center.A 29-year-old woman with severe OHSS after fresh embryo transfer after controlled ovarian hyperstimulation requiring intervention until 21 weeks' gestation in a singleton pregnancy.Thorough evaluation of an unusual case of severe OHSS and medical/procedural management of its sequelae in the setting of ongoing pregnancy.The clinical development of severe OHSS during pregnancy and its effect on pregnancy outcomes.Severe OHSS persisted until 21 weeks' gestation with reaccumulating ascitic fluid, which impacted pregnancy outcomes.Clinicians should be aware of the risk of severe OHSS and its possible effect on pregnancy outcomes beyond the first trimester.

The present study is the first to examine the relations between participation in a public early childhood intervention (the Child-Parent Center (CPC) program) and psychological well-being (or, positive functioning) into early mid-life. Data are drawn from the Chicago Longitudinal Study (CLS), which has followed a cohort of 1,539 individuals who grew up in urban poverty for over four decades. Approximately two-thirds of the original study cohort participated in the CPC program in early childhood; the rest comprise a demographically matched comparison group. Participants’ psychological functioning at age 35–37 was assessed using the Ryff Scales of Psychological Wellbeing. Results support a positive relationship between CPC preschool participation and long-term psychological wellbeing. Moderated mediation (e.g., whether CPC effects on wellbeing differ across subgroups) and potential mechanisms across multiple social-ecological levels (according to the 5-Hypothesis Model of early intervention) are also empirically investigated. Future directions for child development research, early childhood intervention, and public policy are discussed.

The marine coastal region makes up just 10% of the total area of the global ocean but contributes nearly 20% of its total primary production and over 80% of fisheries landings. Unicellular phytoplankton dominate primary production. Climate variability has had impacts on various marine ecosystems, but most sites are just approaching the age at which ecological responses to longer term, unidirectional climate trends might be distinguished. All five marine pelagic sites in the US Long Term Ecological Research (LTER) network are experiencing warming trends in surface air temperature. The marine physical system is responding at all sites with increasing mixed layer temperatures and decreasing depth and with declining sea ice cover at the two polar sites. Their ecological responses are more varied. Some sites show multiple population or ecosystem changes, whereas, at others, changes have not been detected, either because more time is needed or because they are not being measured.

External fixator costs have been shown to be highly variable. Current information on external fixator costs and cost drivers is limited. The aim of this study was to examine the cost variation as well as the patient-, injury-, and surgeon-related cost drivers associated with temporizing external fixation constructs in tibial plateau and pilon fracture management.A retrospective review was conducted to identify isolated tibial plateau and pilon fractures treated with temporizing external fixation from 2006-2018 at a level 1 trauma center. Inclusion criteria were based on fractures managed with primary external fixation, skeletal maturity, and isolated ipsilateral fracture fixation. Fracture patterns were identified radiographically using Schatzker, Weber, and OTA classification systems. Implant costs were determined using direct purchase price from the institution. The primary outcome was the external fixator total construct cost. Clinical covariates and secondary outcomes, namely unplanned reoperations, were extracted. Factors associated with cost (i.e. cost drivers) were identified via multivariable regression analysis.A total of 319 patients were included in this study (121 tibial plateau and 198 pilon fractures). Mean plateau construct cost was $5,372.12 and mean pilon construct cost was $3,938.97. Implant cost correlated poorly with demographic (rThere is large cost variation in temporizing external fixation management. Cost drivers included surgeon bias and implant preference as well as use of external fixator clamps. Introducing construct standardization will contain healthcare spending without sacrificing patient outcomes.Level III. Retrospective Cohort.

Activation of sphingomyelinase (SMase) as a result of a general inflammatory response has been implicated as a mechanism underlying disease-related loss of skeletal muscle mass and function in several clinical conditions including heart failure. Here, for the first time, we characterize the effects of SMase activity on human muscle fibre contractile function and assess skeletal muscle SMase activity in heart failure patients.The effects of SMase on force production and intracellular CaSphingomyelinase reduced muscle fibre force production (-30%, P 0.05) by impairing sarcoplasmic reticulum (SR) CaThe present findings implicate activation of skeletal muscle SMase as a mechanism underlying human heart failure-related loss of muscle mass and function. Moreover, our findings strengthen the idea that SMase activation may underpin disease-related loss of muscle mass and function in other clinical conditions, acting as a common patophysiological mechanism for the myopathy often reported in diseases associated with a systemic inflammatory response.

Telomeres, the natural ends of linear chromosomes, comprise repeat-sequence DNA and associated proteins1. Replication of telomeres allows continued proliferation of human stem cells and immortality of cancer cells2. This replication requires telomerase3 extension of the single-stranded DNA (ssDNA) of the telomeric G-strand ((TTAGGG)n); the synthesis of the complementary C-strand ((CCCTAA)n) is much less well characterized. The CST (CTC1–STN1–TEN1) protein complex, a DNA polymerase α-primase accessory factor4,5, is known to be required for telomere replication in vivo6–9, and the molecular analysis presented here reveals key features of its mechanism. We find that human CST uses its ssDNA-binding activity to specify the origins for telomeric C-strand synthesis by bound Polα-primase. CST-organized DNA polymerization can copy a telomeric DNA template that folds into G-quadruplex structures, but the challenges presented by this template probably contribute to telomere replication problems observed in vivo. Combining telomerase, a short telomeric ssDNA primer and CST–Polα–primase gives complete telomeric DNA replication, resulting in the same sort of ssDNA 3′ overhang found naturally on human telomeres. We conclude that the CST complex not only terminates telomerase extension10,11 and recruits Polα–primase to telomeric ssDNA4,12,13 but also orchestrates C-strand synthesis. Because replication of the telomere has features distinct from replication of the rest of the genome, targeting telomere-replication components including CST holds promise for cancer therapeutics.

From June to October, southern Africa produces one-third of the global biomass burning (BB) emissions by widespread fires. BB aerosols are transported westward over the south-eastern Atlantic with the mid-tropospheric winds, resulting in significant radiative effects. Ascension Island (ASI) is located midway between Africa and South America. From June 2016 to October 2017, a 17-month in situ observation campaign on ASI found a low single-scattering albedo (SSA) as well as a high mass absorption cross-section of black carbon (MACBC), demonstrating the strong absorbing marine boundary layer in the south-eastern Atlantic. Here we investigate the monthly variations of critical optical properties of BB aerosols, i.e. SSA and MACBC, during the BB seasons and the driving factors behind these variations. Both SSA and MACBC increase from June to August and decrease in September and October. The average SSA during the BB seasons is 0.81 at 529 nm wavelength, with the highest mean ∼ 0.85 in October and the lowest ∼ 0.78 in August. The absorption enhancement (Eabs) derived from the MACBC shows similar trends with SSA, with the average during the whole of the BB seasons at ∼ 1.96 and ∼ 2.07 in 2016 and 2017, respectively. As the Eabs is higher than the ∼ 1.5 commonly adopted value by climate models, this result suggests the marine boundary layer in the south-eastern Atlantic is more absorbing than model simulations. We find the enhanced ratio of BC to CO (ΔBC/ΔCO, equal to BC/ΔCO as the BC background concentration is considered to be 0) is well correlated with SSA and MACBC, providing a simple way to estimate the aerosol optical characteristics in the south-eastern Atlantic. The exponential function we proposed can approximate SSA and MACBC with BC/ΔCO, and when BC/ΔCO is small it can capture the rapid growth of SSA as BC/ΔCO decreases. BC/ΔCO is influenced by combustion conditions and aerosol scavenging. From the analysis of the location of BB, the primary source fuel, the water content in the fuel, combined with the mean cloud cover and precipitation in the transport areas of the BB plume, we conclude that the increase in BC/ΔCO from June to August is likely to be caused by burning becoming more flaming. The reduction in the water content of fuels may be responsible for the change in the burning conditions from June to August. The decrease in BC/ΔCO in September and October may be caused by two factors, one being a lower proportion of flaming conditions, possibly associated with a decrease in mean surface wind speed in the burning area, and the other being an increase in precipitation in the BB transport pathway, leading to enhanced aerosol scavenging, which ultimately results in an increase in SSA and MACBC.

We are in the business of research. We are in the business of developing new drug delivery systems. And we are in the business of manufacturing products that help patients, patients who must contend with diseases that diminishes or shortens their lives. At all stages from basic research to final manufacturing, teams are the best way to advance efficiently. Whether it be in academia, where the fundamental science and engineering insights are discovered and elucidated, or in the world of highly structured pharmaceutical development, where a new product must be scrupulously tested and proven to work in patients, our teams have a mission: to make lives better. A team is a group of people who perform interdependent tasks to work toward accomplishing a common mission or specific objective. In this article, we share some strategies for fostering successful teams in drug delivery. We focus here on drug delivery as the field we know the best; but we think many of the points are relevant in many fields. While it is likely in some instances you may be a team leader; it is more likely you will be a member of a team. And so we start with a focus on being a team player.

Since its first suggestion as possible option for liver radioembolization treatment, the therapeutic isotope holmium-166 (166Ho) caught the experts’ attention due to its imaging possibilities. Being not only a beta, but also a gamma emitter and a lanthanide, 166Ho can be imaged using single-photon emission computed tomography and magnetic resonance imaging, respectively. Another advantage of 166Ho is the possibility to perform the scout and treatment procedure with the same particle. This prospect paves the way to an individualized treatment procedure, gaining more control over dosimetry-based patient selection and treatment planning. In this review, an overview on 166Ho liver radioembolization will be presented. The current clinical workflow, together with the most relevant clinical findings and the future prospective will be provided.

Purpose Internet-based business-to-business electronic procurement (B2B e-procurement) systems are rapidly becoming the primary platform for interorganizational transactions and the delivery of products and services in the travel and tourism industries. Therefore, the purpose of this study is to investigate the critical success factors (CSFs) and implementation strategies for B2B e-procurement systems in travel agency supply chains. Design/methodology/approach This study developed a multifaceted evaluation framework that draws on the relevant literature and the technology–organization–environment framework. The CSFs underlying B2B e-procurement adoption were identified using hybrid criteria decision-making methods. Purposive sampling was used, and 49 valid questionnaires were obtained from retail travel agencies in Taiwan. Findings The results reveal that the top four CSFs are system stability, system reliability, sales dynamics and product line availability. By focusing on these CSFs, travel wholesalers can most effectively allocate their limited resources to provide an extensive range of products and services to their clients, improve e-procurement services and enhance interorganizational collaboration in travel agency supply chains. Originality/value This study developed a multifaceted evaluation framework and identified four CSFs to assist in the adoption of B2B e-procurement systems in travel agency supply chains.