Association Between Pre-season Training and Performance in Elite Australian Football.
To examine the association between pre-season training variables and subsequent in-season performance in an elite Australian football team. Data from forty-one elite male Australian footballers (mean±SD: age=23.4±3.1y; height=188.4±7.1cm; mass=86.7±7.9kg) was collected from one Australian Football League (AFL) club. Pre-season training data (external load, internal load, fitness testing and session participation) were collected across the 17-week pre-season phase (6-weeks pre-Christmas, 11-weeks post-Christmas). Champion Data© Player Rank (CDPR), coaches' ratings (CR) and round one selection were used as in-season performance measures. CDPR and CR were examined over the entire season, first half of the season and the first four games. Both Pearson and partial (controlling for AFL age) correlations were calculated to assess if any associations existed between pre-season training variables and in-season performance measures. A median-split was also employed to differentiate between higher and lower performing players for each performance measure. Pre-season training activities appeared to have almost no association with performance measured across the entire season and the first half of the season. However, many pre-season training variables were significantly linked with performance measured across the first four games. Pre-season training variables that were measured post-Christmas were the most strongly associated with in-season performance measures. Specifically, Total on-field session rating of perceived exertion (sRPE) post-Xmas, a measurement of internal load, displayed the greatest association with performance. Late pre-season training (especially on-field match specific training) is associated with better performance in the early season.


Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.
Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes. We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 μg/kg initially; 100 μg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases. Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts. rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.


First Trimester Cystic Hygroma: Herald to Early Diagnosis of Congenital Diaphragmatic Hernia.
The early diagnosis of in utero congenital diaphragmatic hernia (CDH) allows a thorough evaluation for other morbidities that may be associated with CDH. Our patient was referred to us with a fetus at 13 weeks gestational age with a thick nuchal translucency. Our team performed a transvaginal ultrasound that revealed a large ystic hygroma, a heart displaced to the right, and a heterogeneous mass with peristalsis in the left chest. The fetus was diagnosed with CDH. The patient received genetic counseling after which she requested and underwent chorionic villus sampling. The early diagnosis of CDH allows for a timely intervention with the improved management of pre-natal and post-natal care. Better neonatal management is pivotal in providing a multidisciplinary consultation approach in order to furnish accurate counseling and prognostic information for the patient.


[A man with persisting dyspnea].
A 67-year-old male was diagnosed with pulmonary embolism and treated with anticoagulants. Half a year later CT of the chest showed growth of the embolism and that pleural fluid and pleural noduli had appeared. A 18FDG-PET-CT showed uptake in these abnormalities and in several bones. Bone biopsy showed a leiomyosarcoma. The patient was diagnosed with metastasized pulmonary artery sarcoma.


[Myxoma of the heart: symptoms masked by an atrial septal defect].
A 68-year-old woman, known to have a secundum atrial septal defect which had been asymptomatic, reported dyspnea and occasional chest pain for two years. Admission examination revealed orthopnea, cyanosis, polycythemia and inflow congestion of the upper part of the body. After some blood-letting, nifedipine and nitrates brought immediate relief of symptoms. Physical examination, chest x-ray and ECG were not different from previously known findings. All laboratory tests were normal. The findings on cross-sectional echocardiography raised the suspicion of a right ventricular tumor, which was then demonstrated by computed tomography. There were no metastases. Under extracorporeal circulation a right-ventricular benign myxoma, attached to the apical septum and the size of a tennis-ball, was removed. The postoperative course was without complications and the patient was discharged symptom-free.


Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy.
Treatment of severe spasticity and dystonia with intrathecal baclofen (ITB) in children has been shown to be effective and has therefore been employed in the Region of Southern Denmark. The aim of this retrospective study was to analyse the efficacy and adverse events since ITB was introduced in 2003. A total of 46 children who had a baclofen pump from April 2003 to January 2013 were included. The children's medical records were reviewed and clinical characteristics, efficacy and adverse events were registered. The efficacy of treatment experienced by parents was ascertained by telephone interviews, and data were rated on a Likert scale ranging from one to five, where one was no effect and five was marked improvement. After ITB, spasticity was reduced from a median of four to two in the upper extremities and from a median of four to one in the lower extremities. Baclofen infusion was 105.1-2,000 micrograms/day (mean 494.9 micrograms/day). Oral baclofen was reduced from 27.3 to 17.7 mg/day after ITB (p < 0.01). The parents' assessment of improvement in well-being, function and ease of care of their child had a mean score of 3.7, 2.2 and 3.4, respectively. 87.1% of parents stated that ITB had been worthwhile, and 90.3% would recommend it to other parents. Most infectious and mechanical adverse events were experienced during the first 200 days after pump implantation. The total complication rate was 0.40 per pump year. ITB resulted in reduced spasticity in children with severe spasticity and dystonia, and ITB could be considered safe. Parents' satisfaction with ITB was rated as good and most parents would recommend ITB to others. not relevant. not relevant.


Finite statistical complexity for sofic systems.
We propose a measure of complexity for symbolic sequences, which is based on conditional probabilities, and captures computational aspects of complexity without the explicit construction of minimal deterministic finite automata (DFA). Moreover, if the sequence is obtained from a dynamical system through a suitable encoding and its equations of motion are known, we show how to estimate the regions of phase space that correspond to computational states with statistically equivalent futures (causal states).


Fungicide Resistance of Two Species of Alternaria from Potato in the Columbia Basin of Washington.
Fungicides are extensively used in the Columbia Basin of Washington in an effort to manage early blight and brown spot on potato caused by Alternaria solani and A. alternata, respectively. Azoxystrobin and boscalid interfere with cellular respiration, and fungicide resistance is expected to occur in fungal populations due to the narrow modes of action dictated by each fungicide. The objective of this research was to assess A. solani and A. alternata populations in the Columbia Basin of Washington for azoxystrobin and boscalid resistance by initially screening isolates at a threshold concentration using mycelial growth and spore germination. Fifty isolates of A. solani and 58 of A. alternata were randomly selected for screening from 671 isolates collected from potato in the Columbia Basin from 2009 to 2011. Screening at a threshold concentration was done to estimate the range of fungicide resistance within the populations of A. solani and A. alternata in the region. Resistance of five isolates that differed in sensitivity to azoxystrobin and boscalid were then assessed for mycelial growth and spore germination at three fungicide concentrations in order to determine where rates were no longer effective. A. solani mycelial growth ratios and percent spore germination on azoxystrobin-amended media did not change from 2010 to 2011. A slight decrease in resistance of mycelial growth to azoxystrobin was exhibited among A. alternata isolates collected between 2010 and 2011. No change in sensitivity to azoxystrobin was observed in mycelial growth ratios among A. alternata isolates collected between 2010 and 2011. Resistance to boscalid by A. solani increased as indicated by a significant increase in mean mycelial growth ratio from 2010 to 2011, whereas A. alternata showed no change. Spore germination of A. solani was less at 100 μg/ml than at 1 or 10 μg/ml azoxystrobin. Spore germination of A. alternata did not differ among 1, 10, or 100 μg/ml azoxystrobin. Spore germination of A. solani and A. alternata did not differ among 0.5, 5, or 50 μg/ml boscalid. Resistance to azoxystrobin and boscalid in A. solani and A. alternata populations was shown to be present in the Columbia Basin and will likely become widespread with continued used of site-specific fungicides.


Translational regulation of the human achaete-scute homologue-1 by fragile X mental retardation protein.
Fragile X syndrome is a common inherited cause of mental retardation that results from loss or mutation of the fragile X mental retardation protein (FMRP). In this study, we identified the mRNA of the basic helix-loop-helix transcription factor human achaete-scute homologue-1 (hASH1 or ASCL1), which is required for normal development of the nervous system and has been implicated in the formation of neuroendocrine tumors, as a new FMRP target. Using a double-immunofluorescent staining technique we detected an overlapping pattern of both proteins in the hippocampus, temporal cortex, subventricular zone, and cerebellum of newborn rats. Forced expression of FMRP and gene silencing by small interference RNA transfection revealed a positive correlation between the cellular protein levels of FMRP and hASH1. A luciferase reporter construct containing the 5'-untranslated region of hASH1 mRNA was activated by the full-length FMRP, but not by naturally occurring truncated FMR proteins, in transient co-transfections. The responsible cis-element was mapped by UV-cross-linking experiments and reporter mutagenesis assays to a (U)(10) sequence located in the 5'-untranslated region of the hASH1 mRNA. Sucrose density gradient centrifugation revealed that hASH1 transcripts were translocated into a translationally active polysomal fraction upon transient transfection of HEK293 cells with FMRP, thus indicating translational activation of hASH1 mRNA. In conclusion, we identified hASH1 as a novel downstream target of FMRP. Improved translation efficiency of hASH1 mRNA by FMRP may represent an important regulatory switch in neuronal differentiation.


High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma.
The concentration of gamma-aminobutyric acid (GABA) and the activity of glutamate decarboxylase (GAD) in rat and human pancreas were measured by sensitive assay methods. The GABA concentration in rat pancreas was 2.51 millimoles per kilogram (dry weight) and GAD activity was 2.58 mmoles per kilogram per hour. The GABA concentration and GAD activity in rat Langerhans' islets were 18.9 mmole kg-1 and 66.7 mmole kg-1 hour-1, whereas those in the exocrine acini were 1.97 mmole kg-1 and 4.67 mmole kg-1 hour-1, respectively. In an insulinoma region of human pancreas the GABA concentration was 25.5 mmole kg-1 and the GAD activity was 138.2 mmole kg-1 hour-1, but in the surrounding nontumor region these values were only 2.81 mmole kg-1 and 2.01 mmole kg-1 hour-1, respectively, similar to the values in normal rat pancreas.


The anatomic basis for the innervated mylohyoid/digastric flap in facial reanimation.
This paper describes the anatomy of the neurovascular supply to the mylohyoid and digastric muscle and its potential use for a regional transposition to rehabilitate the paralyzed face and soft-tissue coverage in the head and neck area. The anatomy and the arc of rotation of this flap were determined in ten embalmed cadavers. To further demonstrate the vascular supply, the common carotid was injected with silicone in four additional fresh cadavers. In all specimens, the submental artery and the mylohyoid nerve were the sole contributors to the neurovascular supply of the mylohyoid and digastric muscle. The arc of rotation was an average of 5 cm (range 4 to 6.5 cm), which allowed the flap to be positioned appropriately between the zygomatic arch and the modiolus. From this anatomic study, the mylohyoid/digastric flap has a long enough neurovascular pedicle to be useful in facial reanimation and soft-tissue coverage in the head and neck area.


Development and validation of the Screen for Early Eating Disorder Signs (SEEDS) in persons with type 1 diabetes.
This study's objective was to develop and validate an instrument to identify those at risk of developing an eating disorder (ED) in persons with type 1 diabetes. The Screen for Early Eating Disorder Signs (SEEDS) instrument was developed using a multi-phase process including focus groups, cognitive interviews, and mailed questionnaires. Factor analysis revealed 20 items across three factors (Body Image, Feelings, Quality of Life) demonstrating strong psychometric properties. Scoring guidelines and interpretation are provided. SEEDS is a brief (20-item; 2-5 minutes to complete), self-administered, screen designed for use in clinical practice or research to identify or confirm suspicions of ED risk and does not include weight-control behavior items.


Polaron and bipolaron induced charge carrier transportation for enhanced photocatalytic H2 production.
Photocatalysis is one of the facile approaches for efficient solar energy conversion and storage. However, rapid charge carrier recombination considerably decreases solar to energy conversion efficiency. Herein, polaron and bipolaron rich polypyrrole (PPy) has been utilized as a solid support for effective photogenerated charge carrier separation. Simple oxidative polymerization using a high concentration of ammonium persulfate (APS) induces radical cation/bipolaron formation in PPy due to the cleavage of π-bonds as confirmed by electron paramagnetic resonance spectroscopy (EPR). The formation of radical cations led to an increase of the dielectric constant which retards the charge carrier recombination and thereby enhances the conductivity. Moreover, the polarons and bipolarons induced charge carrier separation in photocatalytic H2 production was studied with the well-known g-C3N4 photocatalyst. It is worth mentioning that compared to bare g-C3N4, the PPy supported system showed a drastically enhanced photocatalytic H2 production rate. A maximum H2 production rate of 1851 μmoles per g is achieved, which is ∼51 times higher than that of the bare g-C3N4 catalyst due to efficient charge carrier separation assisted by radical cations/bipolarons. Thus, utilizing this simple polaron and bipolaron rich PPy solid support could be an effective strategy and alternative for using noble metal cocatalysts to enhance charge carrier separation.


[Borrelia burgdorferi-induced pseudolymphoma with pathogen cultivation in an HIV-1 positive patient].
Cutaneous symptoms and skin diseases are common findings in almost all HIV-1-positive patients. In many cases the clinical presentation and course of the skin diseases are atypical, and occasionally the development of the appropriate circulating antibodies is lacking or impaired. In this report we present a patient seen in our multidisciplinary outpatient clinic for HIV patients. This patient had a Borrelia burgdorferi infection with an unusual course. The acute inflammatory phase of the arthropod reaction was maintained over a period of 9 months with development into pseudolymphoma showing unusual cytological characteristics. Immunohistological evaluation revealed an almost complete lack of T-helper and Langerhans cells, but an increased number of activated cytotoxic cells with class II antigen expression. A marked serological response was observed on IgG-ELISA and in the IgG-immunofluorescence test. Borrelia burgdorferi was cultured in vitro from a skin biopsy of the involved area. To our knowledge this is the first reported case of skin borreliosis in an HIV-1-positive patient.


Impact of cognitive-behavioral interventions on weight loss and psychological outcomes: A meta-analysis.
To examine the effects of cognitive-behavioral therapy weight loss (CBTWL) interventions on weight loss, psychological outcomes (eating behaviors [cognitive restraint, emotional/binge eating], and depressive/anxiety symptoms) in adults with overweight or obesity. To be included, studies had to (a) be randomized controlled clinical trials of a CBTWL intervention versus a comparison intervention; (b) include weight loss and psychological outcomes; and (c) include patients who were at least overweight to obese. This review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (Moher, Liberati, Tetzlaff, & Altman & the PRISMA Group, 2009). Twelve studies (6,805 participants) were included. The average weight loss difference between arms was -1.70 kg (95% confidence interval [CI]: -2.52 to -0.86, I2 = 1%) in favor of CBTWL. The standardized mean difference on cognitive restraint was 0.72 (95% CI: 0.33 to 1.09; I2 = 81%) and -0.32 (95% CI: -0.49 to -0.16; I2 = 0%) for emotional eating in favor of CBTWL. The reduction in depressive symptoms was not statistically different between the groups (-0.10 [95% CI: 0.21 to 0.02], I2 = 36%). Meta-analyses were not possible for anxiety and binge eating. In addition to weight loss, current evidence suggests that CBTWL is an efficacious therapy for increasing cognitive restraint and reducing emotional eating. However, CBTWL does not seem to be superior to other interventions for decreasing depressive symptoms. Future studies should focus on understanding how psychological factors impact weight loss and management. (PsycINFO Database Record


Hospitalization rates for respiratory syncytial virus infection in premature infants born during two consecutive seasons.
To collect data on hospitalization rates for respiratory syncytial virus (RSV) illness during the season of 1999 to 2000 in nonprophylaxed premature infants < or = 32 weeks gestational age (GA) in Spain and compare this with previously published data collected in the season of 1998 to 1999. Children born at < or = 32 weeks GA between April 1, 1999, and April 31, 2000, and discharged from the hospital before April 31, 2000, were included. Neonatal and demographic data were obtained at the initial visit. Study subjects were followed at monthly intervals throughout the respiratory season. RSV status and morbidity data were collected on patients rehospitalized for respiratory illness. The 999 evaluable patients in the 2000 season were comparable to the 1999 sample, except for higher rates of family allergy history and number of multiple deliveries and a lower rate of neonatal morbidity. The hospitalization rate for RSV illness was 13.4% in the 1999 season and 13.1% in the 2000 season; 10 (8%) were RSV reinfections in the 2000 season. Significant independent prognostic variables for high risk of RSV hospital admission included: lower gestational age; chronologic age < 3 months at onset of the RSV season; living with school age siblings; and exposure to tobacco smoke. Hospitalization rates for RSV disease in nonprophylaxed preterm infants < or = 32 weeks GA were high in Spain and comparable during two consecutive RSV seasons (13%). Readmission for a second RSV infection was also common.


Comparative Preclinical Biodistribution, Dosimetry, and Endoradiotherapy in Metastatic Castration-Resistant Prostate Cancer Using 19F/177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T.
Radiohybrid prostate-specific membrane antigen (rhPSMA) ligands are applicable as radiochemical twins for both diagnostic PET imaging and endoradiotherapy. On the basis of preliminary data as a diagnostic ligand, the isomer rhPSMA-7.3 is a promising candidate for potential endoradiotherapy. The aim of this preclinical evaluation was to assess the biodistribution, dosimetry, and therapeutic efficacy of 19F/177Lu-rhPSMA-7.3 in comparison to the established therapeutic agent 177Lu-PSMA I&T (imaging and therapy). Methods: The biodistribution of 19F/177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T was determined in LNCaP tumor-bearing severe combined immunodeficiency (SCID) mice after sacrifice at defined time points up to 7 d (n = 5). Organs and tumors were dissected, percentage injected dose per gram (%ID/g) was determined, and dosimetry was calculated using OLINDA/EXM, version 1.0. The therapeutic efficacy of a single 30-MBq dose of 19F/177Lu-rhPSMA-7.3 (n = 7) was compared with that of 177Lu-PSMA I&T in treatment groups (n = 7) and control groups (n = 6-7) using C4-2 tumor-bearing SCID mice by evaluating tumor growth and survival over 6 wk after treatment. Results: The biodistribution of 19F/177Lu-rhPSMA-7.3 revealed fast blood clearance (0.63 %ID/g at 1 h after injection), and the highest activity uptake was in the spleen and kidneys, particularly in the first hour (33.25 %ID/g and 207.6 %ID/g, respectively, at 1 h after injection), indicating a renal excretion pathway. Compared with 177Lu-PSMA I&T, 19F/177Lu-rhPSMA-7.3 exhibited an initial (1 h) 2.6-fold higher tumor uptake in LNCaP xenografts and a longer retention (4.5 %ID/g vs. 0.9 %ID/g at 168 h). The tumor dose of 19F/177Lu-rhPSMA-7.3 was substantially higher (e.g., 7.47 vs. 1.96 µGy/MBq at 200 mm3) than that of 177Lu-PSMA I&T. In most organs, absorbed doses were higher for 177Lu-PSMA I&T. A significantly greater tumor size reduction was shown for a single dose of 19F/177Lu-rhPSMA-7.3 than for 177Lu-PSMA I&T at the end of the experiment (P = 0.0167). At the predefined termination of the experiment at 6 wk, 7 of 7 and 3 of 7 mice were still alive in the 19F/177Lu-rhPSMA-7.3 and 177Lu-PSMA I&T groups, respectively, compared with the respective control groups, with 0 of 7 and 0 of 6 mice. Conclusion: Compared with 177Lu-PSMA I&T, 19F/177Lu-rhPSMA-7.3 can be considered a suitable candidate for clinical translation because it has similar clearance kinetics and a similar radiation dose to healthy organs but superior tumor uptake and retention. Preliminary treatment experiments showed a favorable antitumor response.


Conceptual issues in neurodevelopmental disorders: lives out of synch.
Current revision of the two major psychiatric classification systems has elicited particular comment on neurodevelopmental disorders, which have seen increased provision of specialist clinical services, user group activity, fictional and biographical accounts, and research. Philosophical scrutiny of autism research and literature provides an additional perspective. Neurodevelopmental disorders show considerable overlap neuropsychologically, physiologically and genetically. They overlap diagnostically with schizophrenia, personality disorders, anxiety and depression. Of the two main diagnostic groups, there is more evidence of change with maturation in autism spectrum disorder than attention-deficit hyperactivity disorder. Interventions should combine cognitive, affective and embodied aspects of these disorders, and encompass the individual and their social environment. There is considerable evidence of the toll that caring for people with neurodevelopmental disorders exerts on parents. Neurodevelopmental disorders are multifaceted: research addressed to connection rather than further Balkanization is more likely to be fruitful. Clinicians should consider which facets are displayed symptomatically to enable people to grow through rather than surrender to their impairments. Social scaffolding optimizes functional well being. Future research should take into account the tensions in the relationship between research and user groups, and examine the experiences of adults and of the spouses and partners of those affected.


Microbial community structure and functioning along metal pollution gradients.
Toxic effects of heavy metals on soil microorganisms have been confirmed in a number of laboratory studies. However, most real-field studies do not allow for strong general conclusions due to a range of problems, such as pseudoreplication and confounding factors, which are almost impossible to control for with the most commonly used polluted versus unpolluted or random sampling designs. Effects of metal contamination on soil microbial community traits were measured along 2 pollution gradients in southern Poland. Employing an experimental regression design, using 2 separate gradients, the authors aimed to control for effects of soil properties and beta-diversity of microbial communities. General microbial activity was measured as soil basal respiration rate and substrate-induced respiration, while microbial functional and structural diversity were analyzed with community-level physiological profiles and phospholipid fatty acid patterns, respectively. Metal concentrations were normalized to their toxicity and integrated in a toxicity index (TI). Microbial activity (basal and substrate-induced respiration) decreased in both gradients with increasing TI. Community-level physiological profiles for fungi correlated positively with TI, but no impact of TI on the community-level physiological profiles of bacteria was observed. The phospholipid fatty acids a:15 and i:17 were positively correlated with TI, whereas 16:1ω9 and 18:2ω9 were negatively correlated with TI. The use of 2 gradients (Olkusz and Miasteczko Śląskie) allowed the authors to reveal a clear effect of pollution on general microbial structure and activities, even though they were not able to control completely for all confounding factors. Soil pH, organic matter content, and nutrient level appeared to be at least as important as TI in determining microbial community structure and activities.


STAT RT: a prospective pilot clinical trial of Scan-Plan-QA-Treat stereotactic body radiation therapy for painful osseous metastases.
Planning and treatment of bone metastases with palliative radiotherapy often requires 1-3 weeks, resulting in patient inconvenience and delayed palliation. We developed an expedited workflow that delivers palliative stereotactic body radiation therapy (SBRT) to painful bone metastases in which CT, planning, quality assurance (QA), and initial treatment are performed one day. This prospective pilot clinical trial evaluates the feasibility, safety, efficacy, and patient satisfaction of this workflow. Patients with 1-3 painful bone metastases were prospectively enrolled and treated with 2-5 fractions of 5-10 Gy per fraction. Bone pain, opioid use, patient satisfaction, performance status, and quality of life were evaluated prior to and at 1, 4, 8, 12, 26, and 52 weeks post treatment. Outcomes and treatment-related toxicity were analyzed. Twenty-eight patients were enrolled and 37 metastases treated, receiving an average of 21.6 Gy in 3.1 fractions. Median time from CT simulation to 1st treatment was 6.6 hours. Average worst pain scores were significantly lower at all post-treatment time points with maximal response noted at 3 months. Opioid use was not significantly different from baseline at any follow up. Performance status was significantly increased only at week 12. Bone pain quality of life was significantly increased at all time points except at 52 weeks while general quality of life was significantly increased at only weeks 8 and 26. Ninety-two percent of patients reported being mostly or completely satisfied with the treatment results from week 8 until the end of follow-up. There was no grade 3 or higher toxicities. Results demonstrate that treating bone metastases with palliative SBRT via a multi-fraction Scan-Plan-QA-Treat patient centric workflow is feasible and safe. Although performance status, general quality of life, and opioid use were not significantly altered, patient satisfaction was high with this same-day treatment workflow.


Mercury bougie dilation of benign esophageal strictures.
Dilation with mercury filled bougies is the oldest and simplest technique available for treatment of benign esophageal strictures. In the majority of patients, mercury-filled dilators are effective and quite safe. Dilation is successful in 80-90%, and the rate of complication is less then 0.2%. Maloney dilators have superseded Hurst dilators because their tapered, flexible tip allows better guidance of the dilators into the lumen of the stricture. Several cautions are in order when using Maloney dilators. Dilation of difficult strictures should be observed by fluoroscopy to prevent misdirection of the dilator and esophageal perforation. Where possible, Maloney dilators should not be used to treat narrow, elongated, or angulated strictures. Dilation need not be rushed. Treatments may be repeated over months to years, both to achieve symptomatic relief initially and to maintain that state. Finally, patients susceptible to endocarditis require antibiotic prohylaxis prior to treatment.


SUV39h- and A-type lamin-dependent telomere nuclear rearrangement.
Telomeres are specialized chromatin structures that are situated at the end of linear chromosomes and play an important role in cell senescence and immortalization. Here, we investigated whether changes in histone signature influence the nuclear arrangement and positioning of telomeres. Analysis of mouse embryonic fibroblasts revealed that telomeres were organized into specific clusters that partially associated with centromeric clusters. This nuclear arrangement was influenced by deficiency of the histone methyltransferase SUV39h, LMNA deficiency, and the histone deacetylase inhibitor Trichostatin A (TSA). Similarly, nuclear radial distributions of telomeric clusters were preferentially influenced by TSA, which caused relocation of telomeres closer to the nuclear center. Telomeres also co-localized with promyelocytic leukemia bodies (PML). This association was increased by SUV39h deficiency and decreased by LMNA deficiency. These differences could be explained by differing levels of the telomerase subunit, TERT, in SUV39h- and LMNA-deficient fibroblasts. Taken together, our data show that SUV39h and A-type lamins likely play a key role in telomere maintenance and telomere nuclear architecture.


Inertial Sensor Reliability and Validity for Static and Dynamic Balance in Healthy Adults: A Systematic Review.
Compared to laboratory equipment inertial sensors are inexpensive and portable, permitting the measurement of postural sway and balance to be conducted in any setting. This systematic review investigated the inter-sensor and test-retest reliability, and concurrent and discriminant validity to measure static and dynamic balance in healthy adults. Medline, PubMed, Embase, Scopus, CINAHL, and Web of Science were searched to January 2021. Nineteen studies met the inclusion criteria. Meta-analysis was possible for reliability studies only and it was found that inertial sensors are reliable to measure static standing eyes open. A synthesis of the included studies shows moderate to good reliability for dynamic balance. Concurrent validity is moderate for both static and dynamic balance. Sensors discriminate old from young adults by amplitude of mediolateral sway, gait velocity, step length, and turn speed. Fallers are discriminated from non-fallers by sensor measures during walking, stepping, and sit to stand. The accuracy of discrimination is unable to be determined conclusively. Using inertial sensors to measure postural sway in healthy adults provides real-time data collected in the natural environment and enables discrimination between fallers and non-fallers. The ability of inertial sensors to identify differences in postural sway components related to altered performance in clinical tests can inform targeted interventions for the prevention of falls and near falls.


Potential repurposing of oncology drugs for the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, affecting about 30 million people worldwide. Despite recent advances in understanding its molecular pathology, no mechanism-based drugs are currently available that can halt the progression of AD. Because amyloid-β-peptide (Aβ), a primary component of senile plaques, is thought to be a central pathogenic culprit, several disease-modifying therapies are being developed, including inhibitors of Aβ-producing proteases and immunotherapies with anti-Aβ antibodies. Drug repositioning or repurposing is regarded as a complementary and reasonable approach to identify new drug candidates for AD. This commentary will discuss the clinical relevance of an attractive candidate compound reported in a recent paper by Hayes et al. (BMC Medicine 2013) as well as perspectives regarding the possible repositioning of oncology drugs for the treatment of AD. See related research article here http://www.biomedcentral.com/1741-7015/11/81.


[Orthopedic aspects of vertebral metastases].
The palliative operative treatment for untractable backache due to spinal instability with/without (impendig) neurological deficit in patients with metastatic spine tumor is effective. The aim of treatment consists in improving the quality of live. An operative treatment is justified even in an advanced stage of the disease. The standard operative procedure consists in a posterior stabilisation combined with a decompression and debulking of the tumor.


Resuscitation of the small baby--is there a limit?
Innovations in perinatal care in the last decade, in particular delivery room resuscitations and advanced technologies have probably contributed greatly to improved survival of the small newborns. As a result, progressively smaller and less mature infants are being resuscitated; but some survive with severe neurodevelopmental handicap. There should be guidelines about the lower limits of viability below which no resuscitation should be done. It is the view of many that resuscitation of critically ill small babies should be initiated at birth. Further management will be decided depending on the baby's progress and response. Clinicians have to look into the question of withdrawal of life support in small babies who survive with impairment and chronic illnesses.


Molecular modeling of the M3 acetylcholine muscarinic receptor and its binding site.
The present study reports the results of a combined computational and site mutagenesis study designed to provide new insights into the orthosteric binding site of the human M3 muscarinic acetylcholine receptor. For this purpose a three-dimensional structure of the receptor at atomic resolution was built by homology modeling, using the crystallographic structure of bovine rhodopsin as a template. Then, the antagonist N-methylscopolamine was docked in the model and subsequently embedded in a lipid bilayer for its refinement using molecular dynamics simulations. Two different lipid bilayer compositions were studied: one component palmitoyl-oleyl phosphatidylcholine (POPC) and two-component palmitoyl-oleyl phosphatidylcholine/palmitoyl-oleyl phosphatidylserine (POPC-POPS). Analysis of the results suggested that residues F222 and T235 may contribute to the ligand-receptor recognition. Accordingly, alanine mutants at positions 222 and 235 were constructed, expressed, and their binding properties determined. The results confirmed the role of these residues in modulating the binding affinity of the ligand.


Occupational injury in America: An analysis of risk factors using data from the General Social Survey (GSS).
Although much is known about the distribution of occupational injury in terms of various job and employment factors, considerably less is known about other possible risk factors, particularly those involving psychosocial and organizational factors. These factors have not been emphasized in most injury surveillance systems or large scale, population based surveys. In this study, data from the 2002 General Social Survey (GSS) and NIOSH Quality of Work Life (QWL) module were used to examine the risk of occupational injury in terms of socio-demographic factors, employment characteristics, and organizational factors. The most informative results were obtained from Poisson regression analyses, which identified race, occupational category, and work-family interference as risk factors, and safety climate and organizational effectiveness as protective factors for occupational injury. These results provide guidance for targeting interventions and protective measures to curtail occupational injury in the United States.


Diagnostic ultrasound: a primary care-led service?
A training programme has been proposed for general practitioners (GPs) to perform ultrasound in primary care. This has generated considerable concern among radiologists as to the adequacy and appropriateness of such training. To assess the current provision of ultrasound services to primary care in the former Northern health region of England, the level of interest among GPs in undertaking recommended training, and the willingness or ability of radiology departments to provide it. Postal questionnaires were sent to GPs (n = 334), their practice managers (n = 281) and all clinical directors/heads of radiology departments (n = 19) in the region. Altogether, 67% of GPs, 59% of practice managers, and 68% of radiologists returned questionnaires. Overall, 48% of GPs have open access to obstetric/gynaecological ultrasound compared with 77% for general diagnostic requests. A total of 73% of GPs would prefer an open access service and 15% a practice-based service. Some 48% of GPs were not interested, 36% moderately interested, and 16% very interested in participating in the training programme. Only two out of 13 radiology, departments were willing to provide such training. Despite recommendations from the Royal College of General Practitioners, around half the respondents in this survey do not have direct access to ultrasound for obstetric referrals, and a quarter for non-obstetric referrals. Interest shown by GPs in a primary care-led service is not mirrored by their radiology colleagues. Open access to ultrasound was considered the optimum service, suggesting that resources be targeted at improving hospital services rather than transferring facilities to primary care.


Orofacial Granulomatosis and Crohn Disease: Coincidence or Pattern? A Systematic Review.
To systematically review all cases of orofacial granulomatosis (OFG) and evaluate the association between OFG and Crohn disease (CD). This review was conducted according to PRISMA guidelines and a search of the PubMed, MEDLINE, and Embase databases, and the Cochrane Library in March 2020, using keywords and MeSH terms associated with "orofacial granulomatosis," "Crohn disease," and their variants, with no language restrictions and across all age groups. All relevant articles were accessed in full text. Single case reports and articles on sarcoidosis, allergy, ulcerative colitis, and infectious diseases were excluded from the analysis. We retrieved 507 reports on OFG. The mean age at onset was 23.3 years (range 2-89 years). A total of 240 (47.3%) females and 267 (52.6%) males were included. CD was present in 93 children aged <16 years (68.3%) and in 43 adults (31.9%). In most cases, the OFG appeared before the CD. The most common clinical manifestations were intraoral mucosa abnormalities (n = 251; 49.5%), lower-lip swelling (n = 249; 49.1%), upper-lip swelling (n = 227; 44.7%), and gingivae (n = 193; 38.7%). Patients with concurrent CD were more likely to experience involvement of the buccal sulcus. Key Messages: OFG presents primarily as a solo entity. The OFG that was associated with CD was present in 93 children aged under 16 years (68.3%) and in 43 adults (31.9%). Childhood onset of OFG carries with it a higher risk of developing CD.


Characterization of a novel maitake (Grifola frondosa) protein that activates natural killer and dendritic cells and enhances antitumor immunity in mice.
Grifola frondosa, also known as maitake, is a culinary mushroom with immune-enhancing and antitumor effects. Numerous studies have investigated the activity of maitake polysaccharide extracts, but studies of maitake proteins are scarce. In this study, we purified and characterized a new G. frondosa protein, GFP, from maitake fruiting bodies. GFP is a nonglucan heterodimeric 83 kDa protein that consists of two 41 kDa subunits. GFP induced interferon-γ secretion by murine splenocytes and natural killer cells and activated the maturation of bone marrow-derived dendritic cells (BMDCs) via a TLR4-dependent mechanism. GFP-treated BMDCs promoted a Th1 response and exhibited significant antitumor activity when transferred into tumor-bearing mice. In conclusion, we are the first to reveal the critical role of GFP in modulating the immune response and to link the immune-enhancing effects of maitake to its antitumor activities.


Efficacy of pembrolizumab and comprehensive CD274/PD-L1 profiles in patients previously treated with chemoradiation therapy as radical treatment in bladder cancer.
Chemoradiation therapy (CRT) has been increasingly reported as a possible alternative to total cystectomy (TC) for localized bladder cancer (BC). Pembrolizumab is the standard of care for platinum-refractory metastatic urothelial carcinoma, although it is unknown whether the efficacy of pembrolizumab in patients previously treated with curative CRT varies from the results of benchmark trials. We retrospectively assessed whether the survival benefit of pembrolizumab differs between patients previously treated with TC or CRT as radical treatment. A total of 212 patient records were collected for a logistic regression propensity score model. An independent dataset with next-generation sequencing (n=289) and PD-L1 Combined Positive Score (CPS: n=266) was analyzed to assess whether CRT-recurrent tumor harbors distinct CD274/PD-L1 profiles. Propensity score matching was performed using putative clinical factors, from which 30 patients in each arm were identified as pair-matched groups. There was no significant difference in overall survival from the initiation of pembrolizumab (p=0.80) and objective response rate (p=0.59) between CRT and TC treatment groups. In the independent 289 BC cohort, 22 samples (7.6%) were collected as CRT-recurrent tumors. There was no significant difference in CD274 mRNA expression level between CRT-naïve and CRT-recurrent tumors. The compositions of CD274 isoforms were comparable among all isoforms detected from RNAseq between CRT-naïve (n=267) and CRT-recurrent (n=22) tumors. No actionable exonic mutation in CD274 was detected in CRT-recurrent tumors. PD-L1 CPS was positively correlated with CD274 mRNA expression level, and PD-L1 CPS was comparable between CRT-naïve and CRT-recurrent tumors. The efficacy of pembrolizumab for patients previously treated with CRT was similar to those treated with TC. The enhanced tumor regression by combining programmed cell death protein 1/PD-L1 inhibitor and CRT might be expected only in the concurrent administration.


Contact lens practice in Hong Kong in the new millennium.
We evaluated the contact lens services provided by practitioners in Hong Kong, the fitting habits of the contact lens practitioners and their attitudes regarding the use of orthokeratology (ortho-k) and silicone hydrogel (SH) lenses for overnight wear. Questionnaires were sent to all Hong Kong optometrists licensed to prescribe contact lenses. Two hundred and seventy-five questionnaires (21 per cent) were returned. Most of the respondents (96 per cent) were employed in optical shops and worked in practices that provided contact lens services. The number of new/refit cases per practice per month was about 55, with the percentages of new and refit cases being 48 per cent and 52 per cent respectively. Eighty-eight per cent of the patients were fitted with soft lenses and 10 per cent were fitted with rigid gas permeable (RGP) lenses. Fifty-nine per cent of soft lens patients were fitted with planned replacement (frequent replacement and disposable) soft lenses. Fifty per cent of soft lenses were low water content lenses and 85 per cent of RGP lenses were in low DK (< or = 40) material. Multipurpose solutions and soaking solutions with separate cleaner were the most commonly prescribed care regimens for soft and rigid lenses, respectively. Thirteen per cent of the practitioners provided ortho-k services and the mean number of ortho-k cases per month per ortho-k practitioner was six, the majority of patients being children. DreimLens was the lens design most commonly used and Boston XO the most used material. However, 96 per cent of the responding practitioners had reservations about the practice of ortho-k and the use of SH lenses for overnight wear. The contact lens market in HK is still dominated by soft lenses, particularly planned replacement lenses, whereas the percentage of RGP fits has changed little in the past decade. Few respondents used overnight ortho-k and SH lenses in view of concerns about their efficacy and long-term safety.


Clinical Characteristics and Service Needs of Alternate-Level-of-Care Patients Waiting for Long-Term Care in Ontario Hospitals.
Alternate-level-of-care (ALC) patients waiting for admission to long-term care (LTC) in Ontario hospitals are an important subgroup of ALC patients. Understanding the characteristics of ALC patients waiting for LTC can identify opportunities for alternative discharge options. Characteristics from a sample of 13,915 ALC patients waiting for LTC in acute and complex hospitals were analyzed and compared to those from a sample of 113,046 long-stay home care clients in Ontario. Population-level data were obtained using Ontario's RAI-HC database for the period January 2007 to September 2008. Relative to older long-stay home care clients, ALC patients waiting for LTC admission have more functional impairment and complex health needs. A combination of targeted transitional care and more resource-intensive home care services are needed to successfully address ALC patients' care needs in the community. A substantial portion of ALC patients waiting for LTC placement in acute and complex care hospitals may be more appropriately cared for in community settings if adequate community-centred resources are put in place.


APC promoter 1B deletion in familial polyposis--implications for mutation-negative families.
Over 1500 adenomatous polyposis coli (APC) gene mutations have already been identified as causative of familial adenomatous polyposis (FAP). However, routine genetic testing fails to detect mutations in about 10% of classic FAP cases. Recently, it has been shown that a proportion of mutation-negative FAP cases bear molecular changes in deep intronic and regulatory sequences. In this study, we used direct sequencing, followed by multiplex ligation-dependent probe amplification (MLPA) of genomic DNA from family members, affected by classic FAP. We first reported the family as mutation negative. With the launch of a new version of MLPA kit, we retested the family and a novel full deletion of promoter 1B was detected. The exact breakpoints of the deletion were determined by array comparative genomic hybridization (CGH) and long range polymerase chain reaction (PCR), followed by direct sequencing. The total APC expression levels were investigated by quantitative polymerase chain reaction (qPCR) assay and allele-specific expression (ASE) analysis. The APC gene expression was highly reduced, which indicates causative relationship. We suggest that there is a significant possibility that APC promoter 1B mutations could be found in mutation-negative FAP patients. In the light of our findings it seems reasonable to consider targeted genetic re-analysis of APC promoter 1B region in a larger cohort of unsolved cases.


Off-resonance and non-resonant dispersion of Kerr nonlinearity for symmetric molecules [Invited].
The exact formula is derived from the "sum over states" (SOS) quantum mechanical model for the frequency dispersion of the nonlinear refractive index coefficient n₂ for centrosymmetric molecules in the off-resonance and non-resonant regimes. This expression is characterized by interference between terms from two-photon transitions from the ground state to the even-symmetry excited states and one-photon transitions between the ground state and odd-symmetry excited states. When contributions from the two-photon terms exceed those from the one-photon terms, the non-resonant intensity-dependent refractive index n₂>0, and vice versa. Examples of the frequency dispersion for the three-level SOS model are given. Comparison is made with other existing theories.


Evaluation of a test battery for hemineglect in elderly stroke patients for use by therapists in clinical practice.
Hemineglect is not a single entity, and the syndrome has a number of sensory and motor manifestations. The purpose of this study was a) to measure performance of healthy elderly subjects on a battery of validated tests for hemineglect in order to establish appropriate cut-off scores and b) to assess performance of a large sample of elderly stroke patients in a rehabilitation unit, using the same battery. Tests were selected to identify rate of occurrence of hemineglect in visuo-spatial, representational, pre-motor and personal modalities. The battery was administered to 107 patients with right or left sided brain damage and 43 age-matched controls. Results showed that 39.2% right-sided brain damage), were 'neglecters', scoring below cut-off in one or more tests. Star Cancellation and Line Bisection showed the highest relative sensitivity for visuo-spatial neglect (76.4%) 'Baking Tray Task', the 'Exploratory Motor Task', and utilisation of common objects test for personal neglect are additionally suggested for use in the clinical situation. 'Copying a Daisy' and clock-drawing are not recommended due to low sensitivity and subjectivity in scoring respectively.


Effects of exogenous bile acids (BAs) on growth, lipid profile, digestive enzymes, and immune responses of thinlip mullet, Liza ramada.
An eight-week trial was designed to explore the dietary effects of commercially purchased exogenous bile acids (BAs) on growth, whole-body composition, lipid profile, intestinal digestive enzymes, liver function enzymes, oxidative stress biomarkers, and serum immunity of thinlip mullet, Liza ramada. Four triplicate groups (10.50 ± 0.05 g) were fed four soybean meal (SBM)-based diets supplied with several BAs levels at 0 (control), 50, 130, or 350 mg/kg feed. Results indicated that the growth was significantly increased in groups fed BAs-based diets, especially at 130 mg/kg feed. The body composition analysis showed that feeding fish on diets supplied with BAs up to 130 mg/kg decreased moisture (%) alongside increased crude protein (%). However, the body composition of fish fed a diet with 350 mg BAs/kg had the lowest moisture (%) and the highest crude protein (%). Moreover, there were significant increases in the intestinal (protease, α-amylase, and lipase) enzyme activities in the groups supplied with BAs up to 130 mg BAs/kg. Liver function enzymes (aspartate aminotransferase and alanine aminotransferase enzyme activities) were significantly decreased in BAs-supplemented groups compared to those fed the BAs-free group. On the other hand, the control group had higher total cholesterol, triglycerides, and low-density lipoprotein alongside the lower high-density lipoprotein than BAs-supplemented groups, especially at 350 mg BAs/kg feed. BAs significantly decreased hepatic malondialdehyde concentrations and increased the activity of hepatic catalase, superoxide dismutase, and total antioxidant capacity compared with those reared on the control diet. Serum lysozyme, respiratory burst, and alternative complement activities were significantly increased in BAs-supplied groups, particularly in the group supplied with 130 mg BAs/kg compared to those fed on the control diet. Accordingly, our findings recommend that including 130 mg BAs/kg in an SBM-based diet enhanced the growth, digestive enzyme activities, and liver functions, alleviated oxidative stress, boosted serum immunity, and lowered lipid metabolites in thinlip mullet. These findings will be beneficial for improving the quality of feed prepared for feeding mullets and an effective alternative strategy to support mullet farming.


Investigating rectal toxicity associated dosimetric features with deformable accumulated rectal surface dose maps for cervical cancer radiotherapy.
Better knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. The conventional dose-toxicity model is based on the dose volume histogram, which is the parameter lacking spatial dose information. To overcome this limit, we explore a comprehensive rectal dose-toxicity model based on both dose volume histogram and dose map features for accurate radiation toxicity prediction. Forty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively studied, including 12 with Grade ≥ 2 rectum toxicity and 30 patients with Grade 0-1 toxicity (non-toxicity patients). The cumulative equivalent 2-Gy rectal surface dose was deformably summed using the deformation vector fields obtained through a recent developed local topology preserved non-rigid point matching algorithm. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectum surface dose map (RSDM). The dose volume parameters (DVPs) were calculated from the 3D rectum surface, while the texture features and the dose geometric parameters (DGPs) were extracted from the 2D RSDM. Representative features further computed from DVPs, textures and DGPs by principle component analysis (PCA) and statistical analysis were respectively fed into a support vector machine equipped with a sequential feature selection procedure. The predictive powers of the representative features were compared with the GEC-ESTRO dosimetric parameters D0.1/1/2cm3. Satisfactory predictive accuracy of sensitivity 74.75 and 84.75%, specificity 72.67 and 79.87%, and area under the receiver operating characteristic curve (AUC) 0.82 and 0.91 were respectively achieved by the PCA features and statistical significant features, which were superior to the D0.1/1/2cm3 (AUC 0.71). The relative area in dose levels of 64Gy, 67Gy, 68Gy, 87Gy, 88Gy and 89Gy, perimeters in dose levels of 89Gy, as well as two texture features were ranked as the important factors that were closely correlated with rectal toxicity. Our extensive experimental results have demonstrated the feasibility of the proposed scheme. A future large patient cohort study is still needed for model validation.


Effect of resection margins on dermatofibrosarcoma protuberans of the head and neck.
To determine clinical and surgical factors that affect the recurrence of dermatofibrosarcoma protuberans of the head and neck. Retrospective case series of 32 patients who were seen between 1960 and 1995 with a diagnosis of dermatofibrosarcoma protuberans of the head and neck. Data extracted from patients records included sex, age at diagnosis, tumor site, presence or absence of tumor-free margins, initial and salvage treatment, time to recurrence, and status after last treatment. Academic tertiary care referral center. Surgical excision and radiation therapy. Univariate Kaplan-Meier analysis for recurrence showed the difference in survival to be statistically significant (P < .05) between patients who had wide (> or = 2 cm) surgical margins vs those who had close (< 2 cm) margins. Univariate Kaplan-Meier analysis for recurrence with or without radiation as the grouping variable showed the difference to be statistically significant (P < .01). Similar analyses with sex, age, tumor site, and size of tumor as the grouping variables were not statistically significant. Multivariate Cox regression analysis was used with sex, age, and close or wide margins as variables. Close margins (< 2 cm) had a statistically significant positive correlation with recurrence (P < .05), while sex and age were not associated with recurrence. Surgical margins of at least 2 cm should be used in all cases of dermatofibrosarcoma protuberans of the head and neck to prevent recurrence.


[Broad injury panorama in children who swallowed a battery].
Most ingested batteries in children pass through the gastrointestinal canal without problems. The risk for complications is at its highest if the battery gets stuck in the esophagus or if the child is less than 6 years of age or the size of the battery exceeds 15 mm. Thorough database searches only identified a limited number of articles, all were considered to provide low-grade evidence.


Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity.
Longitudinal characterization of SARS-CoV-2 PCR testing from COVID-19 patient's nasopharynx and its juxtaposition with blood-based IgG-seroconversion diagnostic assays is critical to understanding SARS-CoV-2 infection durations. Here, we retrospectively analyze 851 SARS-CoV-2-positive patients with at least two positive PCR tests and find that 99 of these patients remain SARS-CoV-2-positive after 4 weeks from their initial diagnosis date. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95% CI: 34.3-41.3). Our findings from juxtaposing IgG and PCR tests thus reveal that some SARS-CoV-2-positive patients are non-hospitalized and seropositive, yet actively shed viral RNA (14 of 90 patients). This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term non-hospitalized shedders as a means of characterizing the SARS-CoV-2 infection lifecycle.


The 2021 Bo Lindell Lecture: Inclusive, accountable, transparent: the direction we should take for the benefit of present and future generations.
The International Commission on Radiological Protection (ICRP) is recognised as the de-facto world authority in the field of radiological protection. The ICRP Recommendations have been used as a basis for regulations and policy in almost every country, and with the current review and revision of the System of Radiological Protection, it will continue to make significant contributions in radiation safety for patients, workers, the public, and the environment. In a society undergoing significant change, it is necessary to give careful thought to which groups will be perceived as authoritative organisations by the constituents of the future. The ideal form of an authoritative organisation in the new society of the future is to continue to show how it came to make such recommendations, how it reflected the opinions of interested parties in the process, and how it discloses its records with as much transparency as possible. The question now is what we must do to ensure that decision-making advances in a way that not only makes sense to the present generation, but will be easily consumed by future generations. The path that ICRP is taking to formulate the next set of General Recommendations is doing just that, in line with the key procedural values of INCLUSIVE, ACCOUNTABLE, AND TRANSPARENT.


Lipoprotein lipase: cellular origin and functional distribution.
Lipoprotein lipase (LPL, E.C. 18.104.22.168) is the enzyme responsible for hydrolysis of triacylglycerols in plasma lipoproteins, making the fatty acids available for use by subjacent tissues. LPL is functional at the surface of endothelial cells, but it is not clear which cells synthesize the enzyme and what its distribution is within tissues and vessels. We have searched for specific cell expression of the LPL gene by in situ hybridization using a RNA probe and for the corresponding protein distribution by immunocytochemistry on cryosections of some LPL-producing tissues of guinea pigs. In white and brown adipose tissues, heart and skeletal muscle, and lactating mammary gland, there was positive hybridization for LPL mRNA over all members of the major cell types, indicating that mature and immature adipocytes, muscle cells, and mammary epithelial cells are main sources of LPL. In large vessels, LPL expression was detected in some smooth muscle cells in the media layer. There was no positive hybridization for LPL mRNA over endothelial cells in any of the tissues studied, but there was immunoreaction for LPL protein at endothelial surfaces of all blood vessels. In the kidney, there was strong immunofluorescence at the vascular endothelium, particularly in the glomeruli, but little or no LPL mRNA was detected in the surrounding cells. These observations suggest that in some tissues LPL is synthesized by parenchymal cells and spreads along the vascular mesh. Transfer to the vascular endothelium is, however, not the only route taken by LPL. In the mammary gland most of the enzyme protein appeared to be secreted, partly in association with milk fat droplets.(ABSTRACT TRUNCATED AT 250 WORDS)


Sensitivity of SARS-CoV-2 Detection With Nasopharyngeal Swabs.
Background: SARS-CoV-2-infected subjects have been proven contagious in the symptomatic, pre-symptomatic and asymptomatic phase. The identification of these patients is crucial in order to prevent virus circulation. No reliable data on the sensitivity of nasopharyngeal swabs (NPS) are available because of the lack of a shared reference standard to identify SARS-CoV-2 infected patients. The aim of our study was to collect data on patients with a known diagnosis of COVID-19 who underwent serial testing to assess NPS sensitivity. Methods: The study was a multi-center, observational, retrospective clinical study with consecutive enrollment. We enrolled patients who met all of the following inclusion criteria: clinical recovery, documented SARS-CoV-2 infection (≥1 positive rRT-PCR result) and ≥1 positive NPS among the first two follow-up swabs. A positive NPS not preceded by a negative nasopharyngeal swab collected 24-48 h earlier was considered a true positive. A negative NPS followed by a positive NPS collected 24-48 h later was regarded as a false negative. The primary outcome was to define sensitivity of SARS-CoV-2 detection with NPS. Results: Three hundred and ninety three NPS were evaluated in 233 patients; the sensitivity was 77% (95% CI, 73 to 81%). Sensitivity of the first follow-up NPS (n = 233) was 79% (95% CI, 73 to 84%) with no significant variations over time. We found no statistically significant differences in the sensitivity of the first follow-up NPS according to time since symptom onset, age, sex, number of comorbidities, and onset symptoms. Conclusions: NPS utility in the diagnostic algorithm of COVID-19 should be reconsidered.


Detection of Subclinical Corneal Ectasia after Laser in Situ Keratomileusis: Corvis ST.
Described herein are the cases of 2 patients who underwent bilateral femtosecond-assisted laser in situ keratomileusis (FS LASIK) surgery and subsequently developed unilateral postLASIK ectasia. The fellow eye of both patients was topographically normal, their visual acuity was 20/20, and the patients had no visual symptoms. However, a biomechanical assessment using the Corvis ST tonometer (Oculus Optikgerate GmbH; Wetzlar, Germany) revealed remarkable weakness not only in the ectatic eyes, but also in the fellow eye. Arrangements were made to perform corneal crosslinking for the eyes with manifest ectasia and close follow-up of the fellow eyes.


Multiobjective prioritization methodology and decision support system for evaluating inventory enhancement strategies for disrupted interdependent sectors.
Disruptions in the production of commodities and services resulting from disasters influence the vital functions of infrastructure and economic sectors within a region. The interdependencies inherent among these sectors trigger the faster propagation of disaster consequences that are often associated with a wider range of inoperability and amplified losses. This article evaluates the impact of inventory-enhanced policies for disrupted interdependent sectors to improve the disaster preparedness capability of dynamic inoperability input-output models (DIIM). In this article, we develop the dynamic cross-prioritization plot (DCPP)--a prioritization methodology capable of identifying and dynamically updating the critical sectors based on preference assignments to different objectives. The DCPP integrates the risk assessment metrics (e.g., economic loss and inoperability), which are independently analyzed in the DIIM. We develop a computer-based DCPP tool to determine the priority for inventory enhancement with user preference and resource availability as new dimensions. A baseline inventory case for the state of Virginia revealed a high concentration of (i) manufacturing sectors under the inoperability objective and (ii) service sectors under the economic loss objective. Simulation of enhanced inventory policies for selected critical manufacturing sectors has reduced the recovery period by approximately four days and the expected total economic loss by $33 million. Although the article focuses on enhancing inventory levels in manufacturing sectors, complementary analysis is recommended to manage the resilience of the service sectors. The flexibility of the proposed DCPP as a decision support tool can also be extended to accommodate analysis in other regions and disaster scenarios.


Speech-based characterization of dopamine replacement therapy in people with Parkinson's disease.
People with Parkinson's (PWP) disease are under constant tension with respect to their dopamine replacement therapy (DRT) regimen. Waiting too long between doses results in more prominent symptoms, loss of motor function, and greater risk of falling per step. Shortened pill cycles can lead to accelerated habituation and faster development of disabling dyskinesias. The Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the gold standard for monitoring Parkinson's disease progression but requires a neurologist to administer and therefore is not an ideal instrument to continuously evaluate short-term disease fluctuations. We investigated the feasibility of using speech to detect changes in medication states, based on expectations of subtle changes in voice and content related to dopaminergic levels. We calculated acoustic and prosodic features for three speech tasks (picture description, reverse counting, and diadochokinetic rate) for 25 PWP, each evaluated "ON" and "OFF" DRT. Additionally, we generated semantic features for the picture description task. Classification of ON/OFF medication states using features generated from picture description, reverse counting and diadochokinetic rate tasks resulted in cross-validated accuracy rates of 0.89, 0.84, and 0.60, respectively. The most discriminating task was picture description which provided evidence that participants are more likely to use action words in ON than in OFF state. We also found that speech tempo was modified by DRT. Our results suggest that automatic speech assessment can capture changes associated with the DRT cycle. Given the ease of acquiring speech data, this method shows promise to remotely monitor DRT effects.


Application of vibro-acoustography in prostate tissue imaging.
To evaluate the potential of the imaging modality vibro-acoustography (VA) for imaging of the prostate. Excised cadaver prostate specimens were embedded in tissue mimicking gel to simulate the properties of surrounding soft tissues. The samples were imaged at various depths using a laboratory prototyped VA imaging system. The recorded signals were used for offline processing and image reconstruction. In a selected subgroup of tissue samples, conventional ultrasound (B-mode) and x-ray imaging were performed for further analysis, evaluation, and validation of the VA images. The imaging results of prostate tissue samples indicate the capability of VA imaging to detect prostatic nodules and lesions. In the prostate sample with an adenocarcinoma, the lesion appears with a clear contrast with respect to its surrounding tissue. The VA images could also identify the presence of calcifications deep inside the prostate tissue. Further, quantifications of the imaging results demonstrate that VA imaging has higher sensitivity to detect the calcifications compared to conventional ultrasound imaging. VA is also capable of visualizing prostatic tissue structures and in some cases can identify the anatomical zones. More specifically, the observed higher texture level in peripheral zones demonstrates the ability of VA to differentiate between prostatic anatomical zones. Imaging results of ex vivo prostate tissues, reveals the potency of VA as a promising tool to detect abnormalities, delineate tissue structures and anatomical zones, and locate calcifications. The results of this pilot study suggest that in vivo VA imaging of the prostate may be of clinical utility.


Prolactin stress response does not predict brood desertion in a polyandrous shorebird.
One of the fundamental principles of the life-history theory is that parents need to balance their resources between current and future offspring. Deserting the dependent young is a radical life-history decision that saves resources for future reproduction but that may cause the current brood to fail. Despite the importance of desertion for reproductive success, and thus fitness, the neuroendocrine mechanisms of brood desertion are largely unknown. We investigated two candidate hormones that may influence brood desertion in the Kentish plover Charadrius alexandrinus: prolactin ('parental hormone') and corticosterone ('stress hormone'). Kentish plovers exhibit an unusually diverse mating and parental care system: brood desertion occurs naturally since either parent (the male or the female) may desert the brood after the chicks hatch and mate with a new partner shortly after. We measured the hormone levels of parents at hatching using the standard capture and restraint protocol. We subsequently followed the broods to determine whether a parent deserted the chicks. We found no evidence that either baseline or stress-induced prolactin levels of male or female parents predicted brood desertion. Although stress-induced corticosterone levels were generally higher in females compared with males, individual corticosterone levels did not explain the probability of brood desertion. We suggest that, in this species, low prolactin levels do not trigger brood desertion. In general, we propose that the prolactin stress response does not reflect overall parental investment in a species where different parts of the breeding cycle are characterized by contrasting individual investment strategies.


Ocular surface ectoderm instigated by WNT inhibition and BMP4.
We sought to elucidate how and when the ocular surface ectoderm commits to its differentiation into the corneal epithelium in eye development from human induced pluripotent stem cells (hiPSCs) under the influence of WNT signaling and the actions of BMP4. These signals are key drivers ocular surface ectodermal cell fate determination. It was discovered that secreted frizzled related protein-2 (SFRP2) and Dickkopf1 (DKK1), which are expressed in neural ectoderm, are both influential in the differentiation of hiPSCs, where they act as canonical WNT antagonists. BMP4, moreover, was found to simultaneously initiate non-neural ectodermal differentiation into a corneal epithelial lineage. Combined treatment of hiPSCs with exogenous BMP4 aligned to WNT inhibition for the initial four days of differentiation increased the ocular surface ectodermal cell population and induced a corneal epithelial phenotype. Specification of a surface ectodermal lineage and its fate is thus determined by a fine balance of BMP4 exposure and WNT inhibition in the very earliest stages of human eye development.


Lysosomal enzymes and mannose 6-phosphate receptors in the lacrimal drainage system: Evidence and its potential implications.
To investigate the presence and patterns of lysosomal enzymes and mannose 6-phosophate receptor (MPRs) in human lacrimal drainage system. The study was performed on healthy lacrimal sacs and nasolacrimal ducts obtained from exenteration samples immediately after surgery and frozen at -80°C for subsequent analysis. Soluble proteins' extract was used for enzyme assays, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE), native PAGE, activity staining, and western blot analysis. Membrane proteins were separately assessed for detection of mannose 6-phosphate receptors, MPR 46. Sepharose gels, 4-methylumbelliferyl substrates, and antibodies against common lysosomal enzymes and MPRs were used. Enzyme assays were carried out in triplicate to ascertain the results. Differential lysosomal enzyme activities were documented, and among them acid phosphatase and β-hexosaminidase were found to be high. Western blot analysis using enzyme antibodies and subsequent activity staining confirmed strong signals for moderately expressed enzymes such as fucosidase, glucuronidase, and mannosidase. Membrane extracts demonstrated the presence of MPR 46, which indicates the possible roles of cation-dependent MPRs in lysosomal targeting in human lacrimal drainage system. This study provides a proof of principle for the presence of differential lysosomal activity and mannose 6-phosphate ligand transport receptors in human lacrimal drainage system and hypothesizes the potential implications of their dysfunctions.


Integrated on-capillary instrumentation for gene expression measurement directly from cells.
We studied the fundamental instrumental issues relevant to a capillary-based integrated system to measure expression of a specific gene directly from cells. Samples were introduced into a capillary by use of a syringe pump. All reactions were carried out in a microthermocycler, where a part of the capillary having 1 microL inner volume was used as a reaction vessel. First, cells were lysed by heating to release RNA, followed by deoxyribonuclease (DNase) treatment. Then, reverse transcription-polymerase chain reaction (RT-PCR) was performed to obtain amplified products from the targeted mRNA. Finally, the product was verified by capillary electrophoresis (CE) with laser-induced fluorescence detection. The whole protocol was completed in the system in 3 h. PCR product from beta-actin mRNA in 16 human lymphoblast cells was obtained with a signal-to-noise ratio (S/N) of 3400 +/- 730 (n = 3). Therefore, the system is reproducible and sensitive enough to measure gene expression from a single cell. We show that the amplified fragment from breast cancer-specific mRNA was obtained from cells of breast cancer cell line, but was not obtained from cells of hepatoma cell line. These results therefore lay the foundations for future CE or microchip instrumentation for high-throughput automated gene-expression analysis.


Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy.
Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.


Characterization by 1H NMR of glycosidic conformations in the tetramolecular complex formed by d(GGTTTTTGG).
We have conducted two dimensional NOESY studies on the molecule d(G2T5G2) to characterize the structure of the tetramolecular complex previously identified by calorimetric and spectroscopic studies (1). Analysis of the NOE and exchange cross peaks observed in the NOESY spectra establishes the formation of structured conformations at low temperature (5 degrees C). Significantly, within each strand of these structured conformations, the G1 and G8 residues adopt syn glycosidic torsion angles, while the G2 and G9 residues adopt anti glycosidic torsion angles. Consequently, any structure proposed for the tetramolecular complex of d(G2T5G2) must have alternating G(syn) and G(anti) glycosidic torsion angles within each strand. The implications of this observation for potential structures of the tetramolecular complex of d(G2T5G2) are discussed.


A computational model to predict rat ovarian steroid secretion from in vitro experiments with endocrine disruptors.
A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. Environmental toxicants are a serious health concern, and numerous studies have been devoted to studying the effects of endocrine disrupting chemicals (EDCs). The effects of EDCs on steroidogenic enzymes may influence steroid secretion and thus lead to reproductive toxicity. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model is able to predict ovarian sex steroid concentrations under normal estrous cycle in female rat, and ovarian estradiol concentrations in adult female rats exposed to atrazine, bisphenol A, metabolites of methoxychlor or vinclozolin, and letrozole.


Using environmental bonds to regulate the risks of GM crops: problems and prospects.
We examine the characteristics and limitations of the existing system of tort liability for addressing potential environmental damages from GM crops and consider whether environmental bonding could be used to address these risks. We find that in the case of GM crops, a bonding mechanism would complement some of the strengths of tort liability. Specifically, the bonding mechanism provides some protection against bankruptcy, and also shifts the burden of risk toward life science companies that develop the technology. These factors could encourage additional early research by life science firms. However, a bonding mechanism adds to the regulatory apparatus, and would likely increase administrative costs, over tort liability, for public and private parties. Nevertheless, an attractive possibility is that the cumulative outcomes of bonding, e.g., shifting the risk burden, providing a measure of bankruptcy protection, and introducing an additional regulatory component, would mitigate some of the political and social objections to the environmental release of GM crops.


Utility of sedation for young children undergoing dimercaptosuccinic acid renal scans.
No studies have examined whether use of sedation during a Tc-99 m dimercaptosuccinic acid (DMSA) renal scan reduces patient discomfort. To compare discomfort level during a DMSA scan to the discomfort level during other frequently performed uroradiologic tests, and to determine whether use of sedation during a DMSA scan modifies the level of discomfort. We examined the discomfort level in 798 children enrolled in the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) and Careful Urinary Tract Infection Evaluation (CUTIE) studies by asking parents to rate their child's discomfort level with each procedure on a scale from 0 to 10. We compared discomfort during the DMSA scan and the DMSA image quality between centers in which sedation was used >90% of the time (sedation centers), centers in which sedation was used <10% of the time (non-sedation centers), and centers in which sedation was used on a case-by-case basis (selective centers). Mean discomfort level was highest for voiding cystourethrogram (6.4), followed by DMSA (4.0), followed by ultrasound (2.4; P<0.0001). Mean discomfort level during the DMSA scan was significantly higher at non-sedation centers than at selective centers (P<0.001). No difference was apparent in discomfort level during the DMSA scan between sedation centers and selective centers (P=0.12), or between the sedation centers and non-sedation centers (P=0.80). There were no differences in the proportion with uninterpretable DMSA scans according to sedation use. Selective use of sedation in children 12-36 months of age can reduce the discomfort level experienced during a DMSA scan.


The effect of 3-methylindole on superoxide and hydrogen peroxide production and NADPH oxidation by goat lung microsomes.
The production of superoxide and hydrogen peroxide and the oxidation of NADPH by goat lung microsomes in the presence of 3MI or nitrofurantoin were investigated. Although nitrofurantoin strongly enhanced microsomal formation of adrenochrome from epinephrine (a superoxide dependent reaction), 3MI did not increase the rate of adrenochrome formation by microsomes. Neither 3MI nor nitrofurantoin stimulated significant increases in microsomal hydrogen peroxide production. 3MI tripled NADPH oxidation compared to controls, while nitrofurantoin caused a nearly twenty-fold increase in NADPH oxidation. It is concluded that production of superoxide, hydrogen peroxide and depletion of intracellular stores of reduced pyridine nucleotides are not significant components of 3MI pneumotoxicity.


Evaluation of biological safety in vitro and immunogenicity in vivo of recombinant Escherichia coli Shiga toxoids as candidate vaccines in cattle.
Cattle are the most important reservoir for enterohemorrhagic Escherichia coli (EHEC), a subset of shigatoxigenic E. coli (STEC) capable of causing life-threatening infectious diseases in humans. In cattle, Shiga toxins (Stx) suppress the immune system thereby promoting long-term STEC shedding. First infections of animals at calves' age coincide with the lack of Stx-specific antibodies. We hypothesize that vaccination of calves against Shiga toxins prior to STEC infection may help to prevent the establishment of a persistent type of infection. The objectives of this study were to generate recombinant Shiga toxoids (rStx1mut & rStx2mut) by site-directed mutagenesis and to assess their immunomodulatory, antigenic, and immunogenic properties. Cultures of bovine primary immune cells were used as test systems. In ileal intraepithelial lymphocytes both, recombinant wild type Stx1 (rStx1WT) and rStx2WT significantly induced transcription of IL-4 mRNA. rStx1WT and rStx2WT reduced the expression of Stx-receptor CD77 (syn. Globotriaosylceramide, Gb3) on B and T cells from peripheral blood and of CD14 on monocyte-derived macrophages. At the same concentrations, rStx1mut and rStx2mut exhibited neither of these effects. Antibodies in sera of cattle naturally infected with STEC recognized the rStxmut toxoids equally well as the recombinant wild type toxins. Immunization of calves with rStx1mut plus rStx2mut led to induction of antibodies neutralizing Stx1 and Stx2. While keeping their antigenicity and immunogenicity recombinant Shiga toxoids are devoid of the immunosuppressive properties of the corresponding wild type toxins in cattle and candidate vaccines to mitigate long-term STEC shedding by the reservoir host.


Nonlinear force response of active smooth muscle subjected to small stretches.
Isometrically mounted and electrically stimulated strips of rabbit mesotubarium superius muscles were subjected to sinusoidal length perturbations (delta L) of variable amplitude (0-1% of Lmax) at constant frequency (80 Hz). In both the plateau phase of long-maintained (steady-state) contractions and in brief contraction-relaxation cycles the force perturbation amplitude (delta F) response was directly proportional to delta L (and to the developed force, F) for delta L values less than approximately 0.30% of Lmax. At larger delta L values the magnitude of the delta F response deviated downward from a linear relationship. Statistical analysis of the relationship characterized a "deviation point," the value of delta F and delta L beyond which the delta F response departed from linearity. The value of delta F at the deviation point depended strongly on the developed force, whether it was varied by changing muscle rest length, stimulus strength, or time during a phasic contraction-relaxation cycle. The value of delta L at the deviation point was independent of developed force. Restricting the length of muscle subjected to delta L (while not changing cellular dimensions) showed that the slope of delta F/delta L relationship (the active stiffness) depended inversely on the length of muscle in the system. These findings are consistent with a model in which the active elasticity arises from cross bridges that are borne on myofilaments and that both generate and transmit the muscle force.


[The role of the endothelium in the local vascular reactions of the skeletal muscles].
Chemical de-endothelialization of the m. gastrocnemius' vessels nearly completely blocked the working, reactive and postelongation hyperemia as well as the hyperemia induced with augmentation of the amplitude of intra-vessel pressure pulses. Endothelium seems to take part in the above responses through effects upon the vessels' smooth muscles of a vasodilatory substance released or synthesized by the endothelial cells in the mechanical deformation.


The Role of Self-Compassion in the Job Demands-Resources Model, an Explorative Study among Crisis Line Volunteers.
The job demands-resources (JD-R) model has hardly been studied in volunteer organizations and there is a scarcity of studies evaluating self-compassion as a personal resource within the JD-R model. The present study addresses these gaps in current knowledge, first by examining the applicability of the JD-R model in a crisis line volunteer organization. Second, self-compassion is examined, both in terms of its moderating role on the exhaustion process as well as its role on the motivation process. Structural equation modelling was used for the analyses. The influence on the organizational outcome 'compassion towards others' was examined using a multiple regression analysis. The results showed that the JD-R model has an acceptable fit on this sample and supports the central assumption that exhaustion and motivation are two independent but related processes. This study provides evidence that self-compassion is a valuable addition to the JD-R model, as it has an indirect effect on both processes, and increases the explained variance in compassion towards others by 7% through the exhaustion process and by 3% through the motivational process. These findings point to the importance of focusing on self-compassion in training and supervision in volunteer organizations.


The covariance environment defines cellular niches for spatial inference.
The tsunami of new multiplexed spatial profiling technologies has opened a range of computational challenges focused on leveraging these powerful data for biological discovery. A key challenge underlying computation is a suitable representation for features of cellular niches. Here, we develop the covariance environment (COVET), a representation that can capture the rich, continuous multivariate nature of cellular niches by capturing the gene-gene covariate structure across cells in the niche, which can reflect the cell-cell communication between them. We define a principled optimal transport-based distance metric between COVET niches and develop a computationally efficient approximation to this metric that can scale to millions of cells. Using COVET to encode spatial context, we develop environmental variational inference (ENVI), a conditional variational autoencoder that jointly embeds spatial and single-cell RNA-seq data into a latent space. Two distinct decoders either impute gene expression across spatial modality, or project spatial information onto dissociated single-cell data. We show that ENVI is not only superior in the imputation of gene expression but is also able to infer spatial context to disassociated single-cell genomics data.


Antigenic determinants of measles virus hemagglutinin associated with neurovirulence.
The biological activity of monoclonal antibodies specific for the hemagglutinin protein of measles virus strain CAM recognizing six epitope groups according to their binding properties to measles virus strain CAM/R401 was investigated in vivo in our rat model of measles encephalitis. When injected intraperitoneally into measles virus-infected suckling rats, some monoclonal antibodies modified the disease process and prevented the necrotizing encephalopathy seen in untreated animals. The analysis of measles virus brain isolates revealed emergence of variants that resisted neutralization with the passively transferred selecting monoclonal antibody but not with other monoclonal antibodies. Monoclonal antibody escape mutants were also isolated in vitro, and their neurovirulence varied in the animal model. Sequence data from the hemagglutinin gene of measles virus localize a major antigenic surface determinant of the hemagglutinin protein between amino acid residues 368 and 396, which may be functionally important for neurovirulence. The data indicate that the interaction of antibodies with the measles virus H protein plays an important role in the selection of neurovirulent variants. These variants have biological properties different from those of the parent CAM virus.


Considerations in developing lipid-based nutrient supplements for prevention of undernutrition: experience from the International Lipid-Based Nutrient Supplements (iLiNS) Project.
The International Lipid-Based Nutrient Supplements (iLiNS) Project began in 2009 with the goal of contributing to the evidence base regarding the potential of lipid-based nutrient supplements (LNS) to prevent undernutrition in vulnerable populations. The first project objective was the development of acceptable LNS products for infants 6-24 months and for pregnant and lactating women, for use in studies in three countries (Burkina Faso, Ghana and Malawi). This paper shares the rationale for a series of decisions in supplement formulation and design, including those related to ration size, ingredients, nutrient content, safety and quality, and packaging. Most iLiNS supplements have a daily ration size of 20 g and are intended for home fortification of local diets. For infants, this ration size is designed to avoid displacement of breast milk and to allow for dietary diversity including any locally available and accessible nutrient-dense foods. Selection of ingredients depends on acceptability of flavour, micronutrient, anti-nutrient and essential fatty acid contents. The nutrient content of LNS designed to prevent undernutrition reflects the likelihood that in many resource-poor settings, diets of the most nutritionally vulnerable individuals (infants, young children, and pregnant and lactating women) are likely to be deficient in multiple micronutrients and, possibly, in essential fatty acids. During ingredient procurement and LNS production, safety and quality control procedures are required to prevent contamination with toxins or pathogens and to ensure that the product remains stable and palatable over time. Packaging design decisions must include consideration of product protection, stability, convenience and portion control.


Deficient antigen-presenting cell function in multiple genetic complementation groups of type II bare lymphocyte syndrome.
The absence of HLA class II gene expression in type II bare lymphocyte syndrome (BLS) results from defective transcriptional activation of class II histocompatibility genes. Genetic studies have revealed that distinct defects in multiple trans-acting factors result in the immunodeficient BLS phenotype. We studied antigen-presenting cell (APC) function in DR-transfected BLS cells derived from multiple complementation groups. Each BLS cell line displayed the same defective APC phenotype: an inability to mediate class II-restricted presentation of exogenous protein antigens, and structurally altered class II alpha beta dimers. Expression of the HLA class II-like genes DMA and DMB, previously implicated in antigen presentation, was reduced or absent in the BLS cells. Fusion of BLS cells with cell line 721.174, which has a genomic deletion of HLA class II genes, coordinately restores class II structural gene and DM gene expression and a wild-type APC phenotype. Thus each of the molecular defects that silences class II structural gene transcription also results in a defective APC phenotype, providing strong evidence for coregulation of these two functionally linked pathways.


Polymorphisms/haplotypes in DNA repair genes and smoking: a bladder cancer case-control study.
Bladder cancer is associated with tobacco smoking and occupational exposure. The repair of DNA damage has a key role in protecting the genome from the insults of cancer-causing agents. We analyzed 13 polymorphisms in seven DNA repair genes belonging to different repair pathways [X-ray repair cross-complementing group 1 (XRCC1): 26304C>T, 26651A>G, 28152A>G; xeroderma pigmentosum-D (XPD): 23591A>G, 35931A>C; excision repair complementing defective in Chinese hamster, group 1 (ERCC1): 19007C>T; XRCC3: 4541T>C, 17893A>G, 18067C>T; proliferating cell nuclear antigen (PCNA): 6084G>C; ERCC4: 30028C>T, 30147A>G; and XRCC2-31479A>G] in 317 incident bladder cancer patients and 317 controls. After adjustment for age and smoking, the PCNA-6084C variant was significantly associated with an increased risk of bladder cancer [CC + CG versus GG, odds ratio (OR), 1.61; 95% confidence interval (95% CI), 1.00-2.61], as well as the XRCC1-26651G variant (GG+AG versus AA: OR, 1.73; 95% CI, 1.17-2.56). After stratifying by smoking habits, an elevated risk for carriers of the XRCC3-18067T allele was detected both in current (TT versus CC: OR, 2.65; 95% CI, 1.21-5.80; CT versus CC: OR, 1.96; 95% CI, 1.09-3.52) and never smokers (TT versus CC: OR, 4.34; 95% CI, 1.14-16.46; CT versus CC: OR, 2.02; 95% CI, 0.72-5.66), whereas an opposite and slightly weaker effect was associated to the XRCC3-17893G allele in current smokers (GG versus AA: OR, 0.30; 95%CI, 0.11-0.82; AG versus AA: OR, 0.73; 95% CI, 0.42-1.27). XRCC3,XRCC1, ERCC4, and XPD-ERCC1 haplotype frequencies were estimated by the maximum likelihood method. The XRCC3-TAT haplotype was associated with an enhanced risk in the current smokers group (OR, 1.62; 95% CI, 1.15-2.29), whereas a reduction of the risk in the overall sample was observed in the presence of the XRCC3-TAC (OR, 0.69; 95% CI, 0.50-0.97). A significant protective effect of the XPD-ERCC1-ACC haplotype was observed among never smokers (OR, 0.16; 95% CI, 0.03-0.81). Our results suggest that polymorphisms and/or haplotypes in XRCC3, XRCC1, and PCNA genes and spanning XPD-ERCC1 region may modulate bladder cancer risk and that some of these effects may preferentially affect current smokers.