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Purpose: To explore muscle properties, gross motor performance, and quality of life (QoL) in children with sickle cell disease (SCD) compared with controls and to assess relationships among these outcomes., Methods: A cross-sectional study of 24 children assessed muscle properties including: knee extension strength by dynamometry; vastus lateralis (VL) and rectus femoris (RF) muscle thickness by ultrasonography; and VL and RF neuromuscular activation (rate of muscle activation [RoA]) by electromyography (EMG). Gross motor performance and QoL were assessed by standardized tests and questionnaires., Results: Children with SCD had impaired knee extension strength, VL EMG RoA, gross motor performance, and QoL compared with children without SCD. Relationships among muscle properties, gross motor performance, and QoL were identified., Conclusions: These findings indicate that comprehensive muscle properties, gross motor performance, and QoL assessments should be considered to support and develop individualized physical therapy plans for children with SCD., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

The UK, as the "cocaine capital of Europe," currently accounts for ∼75% of all cocaine-related hospital admissions in Europe. This study aims to analyze the trends in cocaine-related deaths in England, Wales and Northern Ireland over 20 years (2000-2019). Cases reported to the National Programme on Substance Abuse Deaths (NPSAD) occurring between 2000 and 2019 where cocaine was detected at post-mortem (PM) were extracted for analysis. A total of 5,339 cases were retrieved, with an increase in the rate of reporting over time. Cocaine was deemed a cause of death and quantified in PM blood samples along with its major metabolite benzoylecgonine in 685 cases. Of these 685 cases, 25% (n = 170/685) occurred following acute use, 22% (n = 154/685) following chronic/binge use, 40% (n = 271/685) in combination with morphine, 4% (n = 29/685) in drug packer/swallower circumstances and 9% (n = 61/685) in a suicide context. Cardiac complications were evident in 22% of cases (n = 154/685). The average concentration of cocaine detected in cardiac cases (900 ng/mL) was considerably lower than that detected in cases where acute (19,100 ng/mL) or chronic/binge (6,200 ng/mL) dosing was evident. This is the first cocaine-related mortality study in these geographical areas. Deaths following cocaine use continue to rise despite its Class A drug listing in the UK. While underlying and external risk factors including polydrug use, cardiac complications and mental health can all contribute to the incidence of fatal drug toxicity following cocaine use, this study demonstrates that the risk of a cocaine overdose cannot be attributed to a specific blood concentration range., (© The Author(s) 2023. Published by Oxford University Press.)

Children with hematologic and oncologic health conditions are at risk of impaired skeletal muscle strength, size, and neuromuscular activation that may limit gross motor performance. A comprehensive assessment of neuromuscular function of these children is essential to identify the trajectory of changes in skeletal muscle and to prescribe therapeutic exercise and monitor its impact. Therefore, this review aims to (a) define fundamental properties of skeletal muscle; (b) highlight methods to quantify muscle strength, size, and neuromuscular activation; (c) describe mechanisms that contribute to muscle strength and gross motor performance in children; (d) recommend clinical assessment measures; and (e) illustrate comprehensive muscle assessment in children using examples of sickle cell disease and musculoskeletal sarcoma.

Background: Medical and surgical treatment for musculoskeletal sarcoma (MSS) place survivors at risk for impairments in muscle properties including muscle strength, muscle size, and neuromuscular activation. The purpose of this study was to explore muscle properties, gross motor performance, and quality of life (QoL) and the changes in response to a 6-week functional strengthening intervention (PT-STRONG) in MSS survivors of childhood cancer (CCS)., Methods: Eight lower extremity MSS CCS (13-23 years old) performed baseline testing and three completed PT-STRONG. Participants completed measurements of knee extension strength using handheld dynamometry, vastus lateralis (VL) and rectus femoris (RF) muscle thickness using ultrasonography at rest, and neuromuscular activation using electromyography during strength testing and a step-up task. Participants also completed gross motor and QoL assessments., Results: Compared with the non-surgical limb, MSS CCS had lower surgical limb knee extension strength, VL muscle thickness, and RF step-up muscle rate of activation (RoA). Compared with normative values, MSS CCS had decreased bilateral knee extension strength, gross motor performance, and physical QoL. Positive correlations among muscle strength, muscle thickness, and gross motor performance were identified. After PT-STRONG, MSS CCS had improvements in VL muscle thickness, VL and RF RoA duing step-up, gross motor performance, and physical QoL., Conclusions: Positive association between larger muscle thickness with greater knee extension strength, and higher knee extension strength with better gross motor performance indicate that comprehensive physical therapy assessment and interventions that identify and target impairments in muscle properties to guide clinical decision making should be considered for MSS CCS into survivorship., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Ultrasound imaging is important in many fields such as medicine, sports, and health sciences to assess parts of muscle structure (e.g., muscle thickness [MT]) or composition (subcutaneous tissue [Sub T ])., Objective: The aim of the present study was to investigate the intra- and inter-rater reliability of MT and Sub T measurements of the hip abductor muscles gluteus medius (GM) and tensor fascia latae (TFL)., Design: Cross-sectional study., Method: Twenty young adults participated in the study. Intra-rater reliability was established by measuring the same two images twice by the same rater, while inter-rater reliability was assessed between two raters by measuring the same two images for each muscle. For both intra- and inter-rater reliability, the reliability of the TFL and GM outcomes (MT- Sub T ) were determined by the intraclass correlation coefficient (ICC), coefficient of variation (CV), standard error of the measurement (SEM), and Bland-Altman plots., Results: For intra-rater reliability, variables of both muscles showed an excellent ICC (≥0.90), lower CV and SEM, and bias near zero. Inter-rater reliability also showed an excellent ICC for both variables and muscles (≥0.81) with lower CV, SEM, and bias., Conclusion: Therefore, these results provide strong evidence of a reliable measure of MT and Sub T from GM and TFL. The present study provides health care professionals and researchers increased confidence in using 2D ultrasound to assess the hip abductors muscles reliably., Competing Interests: Declaration of competing interest All the authors declare no conflicts of interest exist., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Diaphragm ultrasound (DUS) is a noninvasive method of evaluating the diaphragm's structure and function. This study explored the relationships between DUS, spirometry, and respiratory mouth pressures in 10 healthy children (median age: 11 [range: 7-14 years]; 5 females, 5 males). Thickening fraction correlated with maximal inspiratory pressure (MIP) (Spearman's rho [r s ] = 0.64, p = 0.05). During quiet breaths, excursion time correlated with MIP (r s = 0.78, p = 0.01) while velocity correlated with maximal expiratory pressure (r s = -0.82, p = 0.01). During deep breaths, MIP correlated with excursion (r s = 0.64, p = 0.05) and time (r s = 0.87, p = 0.01). Excursion time during deep breaths also correlated with forced vital capacity (r s = 0.65, p = 0.04). Our findings suggest that DUS parameters are closely related to spirometry and respiratory mouth pressures in healthy children and further support the use of DUS as a noninvasive method of respiratory assessment., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To examine physical impairments and physical function in children and adolescents with sickle cell disease (SCD)., Data Sources: PubMed, Embase (embase.com), Cumulative Index to Nursing and Allied Health (EBSCO), Cochrane Central Register of Controlled Trials (Wiley), and Dissertations and Theses (ProQuest) were searched from January 1, 1990, to September 25, 2020. References retrieved were required to include a term for SCD and a term for physical impairments or physical function. Results were limited to articles with children and adolescents and in the English language., Study Selection: A total of 3054 nonduplicate articles were independently screened by 2 reviewers, resulting in 240 articles for full-text review. The full-text review, performed by 2 independent reviewers, resulted in 67 articles., Data Extraction: Data were extracted from each full text to a custom Excel document by a single reviewer and were verified by a secondary reviewer., Data Synthesis: The studies identified in this systematic review offer evidence that children and adolescents with SCD demonstrate physical impairments and physical function limitations compared with control participants as noted by varying percentages in deficits up to 19%-58% in muscle and bone composition and/or symptoms, muscle strength, cardiopulmonary function, motor performance, physical activity, and physical function domains of quality of life questionnaires., Conclusions: Children and adolescents with SCD present with physical impairments and physical function limitations. Scientists and clinicians should consider developing collaborative standards to define and objectively measure physical impairment and function in this population to comprehensively examine the underlying factors that contribute to physical impairments and function., (Copyright © 2021 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: This quasi-experimental study examined the efficacy of targeted exercise training on gross motor performance and neuromuscular impairments in survivors of childhood acute lymphoblastic leukemia (ALL CCS)., Materials and Methods: Ten ALL CCS (median age: 10 years; range: 6-14 years) performed a 6-week training program three times per week (five in-person sessions), including a warm-up, total body stretching, progressive jump rope training, and a cool down. Gross motor performance (test of gross motor proficiency) and lower extremity rate of muscle activation (electromyography), joint torques (motion capture and force plate), and jump height (motion capture) were measured during a countermovement jump at baseline and post-training., Results: Post-training, ALL CCS demonstrated improvements in body coordination, strength and agilty, bilateral coordination, running speed and agility, and strength gross motor performance (mean change: 1.6-8.1; p < 0.05), the rate of muscle activation of the tibialis anterior and vastus lateralis muscles (mean change: 0.58-0.75; p < 0.05), hip and ankle joint torques (mean change: 0.07; p < 0.05), and jump height (mean change: 0.05; p < 0.05)., Conclusion: This study demonstrated that targeted exercise training can improve gross motor performance and neuromuscular impairments in ALL CCS post-medical treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marchese, Rock, York, Ruble and Gray.)

Desalination drinking water systems and industrial processes generating high salinity streams require practical brine management options for disposal and/or treatment. Treatment most often involves large capacity brine concentrating processes, on the order of 2000 m 3 /day, that rely on water evaporation, vapor compression, and condensation. A new technology adds an aerosol-generating device to the evaporation step with the goal of energy efficient operation even at smaller scales. The principles behind the tornadic flowfield that breaks up and aerosolizes water as air and water flow over the machined surface in the device are introduced. Design of a 6.8 m 3 /day demonstration system, based on this new technology, producing a NaCl slurry (55 wt% solids) from a 22 wt% NaCl influent is described. Simulations of the system with three influent brine concentrations and three forms of final NaCl concentrate are presented and predicted energy usage is compared to estimates for conventional systems. By varying simulation process parameters, the heat transfer performance of the evaporator/condenser is identified as having a large impact on overall efficiency. The new system is anticipated to be most competitive, on an energy usage basis, with conventional concentrator/crystallizer systems when processing higher salinity brines and producing final concentrates containing precipitated NaCl.

Understanding the physiological variables that contribute to a functional task provides important information for trainers and clinicians to improve functional performance. The hip abductors and adductors muscles appear to be important in determining the performance of some functional tasks; however, little is known about the relationship of the hip abductor/adductors muscle strength, activation, and size with functional performance. This study aimed to investigate the relationship of maximum torque, rate of torque development (RTD), rate of activation (RoA), and muscle thickness of the hip abductors [tensor fascia latae (TFL) and gluteus medius (GM)] and adductor magnus muscle with the Four Square Step Test (FSST) and the two-leg hop test in healthy young adults. Twenty participants (five males) attended one testing session that involved ultrasound image acquisition, maximal isometric voluntary contractions (hip abduction and hip adduction) while surface electromyography (EMG) was recorded, and two functional tests (FSST and two-leg side hop test). Bivariate correlations were performed between maximum voluntary torque (MVT), RTD at 50, 100, 200, and 300ms, RoA at 0-50, 0-100, 0-200, and 0-300, and muscle thickness with the dynamic stability tests. For the hip abduction, MVT ( r =-0.455, p =0.044) and RTD 300 ( r =-0.494, p =0.027) was correlated with the FSST. GM RoA 50 ( r =-0.481, p =0.032) and RoA 100 ( r =-0.459, p =0.042) were significantly correlated with the two-leg side hop test. For the hip adduction, there was a significant correlation between the FSST and RTD 300 ( r =-0.500, p =0.025), while the two-leg side hop test was correlated with RTD 200 ( r =0.446, p =0.049) and RTD 300 ( r =0.594, p =0.006). Overall, the ability of the hip abductor and adductor muscles to produce torque quickly, GM rapid activation, and hip abductor MVT is important for better performance on the FSST and two-leg hop tests. However, muscle size appears not to influence the same tests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lanza, Rock, Marchese, Addison and Gray.)

Backround: The purpose of this study is to assess the impact of trimodal therapy [surgery, chemotherapy and external beam radiotherapy (EBRT)] in patients with anaplastic thyroid cancer (ATC) treated with curative intent., Materials and Methods: Retrospective review of patients with ATC treated at a tertiary referral centre between January 2009 and June 2020. Data were collected regarding demographics, histology, staging, treatment and outcomes., Results: Seven patients (4 female) were identified. Median age was 58 years (range 52-83 years). All patients received EBRT with concurrent doxorubicin. Six patients received surgery followed by chemoradiotherapy (CRT), and one underwent neoadjuvant CRT followed by surgery. Median radiological tumour size was 50mm (range 40-90 mm). Six patients had gross extrathyroidal extension and three had N1b disease. Prescribed radiotherapy schedules were 46.4 Gy in 29 bidaily fractions (n = 2, treated 2010), 60 Gy in 30 daily fractions (n = 2), 66 Gy in 30 fractions (n = 2) and 70 Gy in 35 fractions (n = 1; patient received neoadjuvant CRT). CRT was discontinued early for two patients due to toxicities. At median follow up of 5.8 months, 42.9% (3/7) patients were alive and disease-free. Only one patient developed a local failure. Three patients died from distant metastases without locoregional recurrence., Conclusions: Despite poor prognosis of ATC, selected patients with operable tumours may achieve high locoregional control rates with trimodal therapy, with possibility of long-term survival in select cases., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest., (© 2021 Greater Poland Cancer Centre.)

Aims: Muscle strength testing is a core aspect in the pediatric physical and occupational therapy clinical examination and evaluation, and quadriceps muscle strength is associated with the ability to perform gross motor skills. The aim of this study was to assess the reliability of handheld dyamometry (HHD) and ultrasonography to measure quadriceps muscle strength and thickness in children, adolescents, and young adults. Methods : In 30 participants (6-26 years), without motor impairment, quadriceps strength was measured with HHD in seated and supine with the knee flexed to 90° and 35°. Rectus femoris (RF) and vastus lateralis (VL) muscle thickness was measured using ultrasonography. Typical error of measurement (TEM), coefficient of variation (CV%), and intra-class correlation coefficient (ICC) were used to assess the error and reliability of measures. Results : The average CV% among three trials of strength testing was 7.07%-9.94% and improved when using the top two trials (4.49%-5.61%). The average TEM was 2.21 Nm for strength and 0.03 cm for muscle thickness. Intra-rater and inter-rater reliability of muscle thickness was good to excellent (0.91-1.00). Conclusions: The results of this study suggest quadriceps muscle strength and thickness measurements using HHD and ultrasonography are reliable in children, adolescents, and young adults.

Purpose: This study explored neuromuscular mechanisms and clinical measures that contribute to countermovement jump performance in survivors of childhood acute lymphoblastic leukemia (ALL CCS) compared to age- and sex-matched peers., Methods: This exploratory cross-sectional observational study examined 12 participants, six ALL CCS and six age- and sex-matched peers (7-16 years). During a countermovement jump, rates of muscle activation of lower leg muscles were measured with electromyography, and joint torques and peak jump height with force plates and a motion capture system. Clinical measures included muscle extensibility, balance, and mobility measured by active ankle dorsiflexion, Bruininks-Oseretsky Motor Proficiency (BOT-2), and Timed Up and Go (TUG) tests., Results: Compared to peers, ALL CCS demonstrated reduced gastrocnemius muscle extensibility and tibialis anterior rate of muscle activation, decreased jump height, and poorer performance on the BOT-2 and TUG. Jump height was significantly correlated with clinical measures of the BOT-2 and TUG., Conclusion: These ALL CCS demonstrated neuromuscular impairments that may impact jump performance, an essential childhood physical activity. Further research is needed to explore intervention strategies to improve the neuromuscular mechanisms that contribute to high-level gross motor skills in ALL CCS.

Subungal squamous cell carcinoma (SSCC) is a rare malignancy of the nail bed. We present the case of a woman diagnosed with a SSCC of the right thumb. Initial management consisted of surgically excision followed by adjuvant radiotherapy due to a positive bone margin. We describe the patient set-up, immobilisation technique, target volume delineation, radiotherapy planning, fractionation schedule, image guidance and patient outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Background: Patients with resected oral cavity squamous cell carcinoma (OCSCC) are often treated with adjuvant radiation (RT) ± concomitant chemotherapy based on pathological findings. Standard RT volumes include all surgically dissected areas, including the tumour bed and dissected neck. RT has significant acute and long-term toxicities including odynophagia, dysphagia, dermatitis and fibrosis. The goal of this study is to assess the rate of regional failure with omission of radiation to the surgically dissected pathologically node negative (pN0) hemi-neck(s) compared to historical control, and to compare oncologic outcomes, toxicity, and quality of life (QoL) profiles between standard RT volumes and omission of RT to the pN0 neck., Methods: This is a multicentre phase II study randomizing 90 patients with T1-4 N0-2 OCSCC with at least one pN0 hemi-neck in a 1:2 ratio between standard RT volumes and omission of RT to the pN0 hemi-neck(s). Patients will be stratified based on overall nodal status (nodal involvement vs. no nodal involvement) and use of concurrent chemotherapy. The primary endpoint is regional failure in the pN0 hemi-neck(s); we hypothesize that a 2-year regional recurrence of 20% or less will be achieved. Secondary endpoints include overall and progression-free survival, local recurrence, rate of salvage therapy, toxicity and QoL., Discussion: This study will provide an assessment of omission of RT to the dissected pN0 hemi-neck(s) on oncologic outcomes, QoL and toxicity. Results will inform the design of future definitive phase III trials., Trial Registration: Clinicaltrials.gov identifier: NCT03997643 . Date of registration: June 25, 2019, Current version: 2.0 on July 11 2020.

Objectives: Sexual health problems have been identified as an unmet need in head and neck cancer (HNC) survivors. In particular, little is known about such outcomes in survivors of nasopharyngeal cancer (NPC)., Materials and Methods: A cross-sectional study of NPC survivors with ≥4y follow-up was undertaken. Sexual satisfaction was assessed using the optional "I am satisfied with my sex life" item of the FACT-H&N. Other patient-reported outcomes measures were also captured including fatigue (FACIT-F), HNC symptom burden (MDASI-HN), emotional distress (HADS) and frontal function (FrSBE). Univariate and multivariate analyses were performed to determine factors influencing sexual satisfaction., Results: The sexual satisfaction item was answered by 85/103 (83%) enrollees. Female (p < 0.001) and non-partnered (p = 0.0045) patients were more likely to abstain from answering. The distribution of responses were: "very much" (26%), "quite a bit" (21%), "somewhat" (20%), "a little bit" (13%) and "not at all" (20%). Sexual satisfaction was associated with multiple patient-reported measures on univariate analysis, including quality of life, fatigue, a priori selected HNC symptoms (pain, taste), emotional distress, frontal lobe function, body image and relationship strength. On multivariate analysis, only relationship strength and emotional distress remained significant. Sociodemographic factors (age, sex, marital status) and other selected orofacial toxicities were not significant., Conclusions: Nearly half (47%) of our sample reported being in the higher satisfaction range. While reassuring in the context of comparative population level data, a number of factors including toxicity, psychological and social factors were associated with sexual satisfaction responses. Prospective evaluation of this unmet need is required., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Osteosarcoma and Ewing's sarcoma are the most common primary bone malignancies affecting children and adolescents. Optimal treatment requires a combination of chemotherapy and/or radiation along with surgical removal when feasible. Advances in multiple aspects of surgical management have allowed limb salvage surgery (LSS) to supplant amputation as the most common procedure for these tumors. However, individuals may experience significant impairment after LSS, including deficits in range of motion and strength that limit function and impact participation in work, school, and the community, ultimately affecting quality of life. Muscle force and speed of contraction are important contributors to normal function during activities such as gait, stairs, and other functional tasks. Muscle architecture is the primary contributor to muscle function and adapts to various stimuli, including periods of immobilization-protected weightbearing after surgery. The impacts of LSS on muscle architecture and how adaptations may impact deficits within the rehabilitation period and into long-term survivorship is not well-studied. The purpose of this paper is to [1] provide relevant background on bone sarcomas and LSS, [2] highlight the importance of muscle architecture, its measurement, and alterations as seen in other relevant populations and [3] discuss the clinical relevance of muscle architectural changes and the impact on muscle dysfunction in this population. Understanding the changes that occur in muscle architecture and its impact on long-term impairments in bone sarcoma survivors is important in developing new rehabilitation treatments that optimize functional outcomes., (Copyright © 2020 Nelson, Marchese, Rock, Henshaw and Addison.)

Objectives: To identify body impairments, activity limitations, and participation restrictions in children, adolescents, and young adults with cancer amenable to rehabilitation, and provide the recommended screening, assessment and rehabilitation referral information for the health care community., Data Sources: A review of the rehabilitation and pediatric oncology literature regarding functional impairments in combination with clinical expertise from practicing pediatric oncology rehabilitation therapists., Conclusion: Rehabilitation intervention has great potential to mitigate the impact of cancer and its treatment and may even have a role in reducing morbidity and mortality. All health care providers have a role in optimizing the function and quality of life in the pediatric cancer population., Implications for Nursing Practice: It is imperative for nurses to utilize subjective and clinical screening to identify persons appropriate for rehabilitation referral, collaborate with the rehabilitation team, and support the patients and families in adhering to rehabilitation recommendations., Competing Interests: Conflict of Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW)., Methods and Materials: This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (<65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status., Results: Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P = .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW., Conclusions: The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report the complete genome sequencing of the first fish peribunyavirus determined using a next-generation sequencing approach. The virus was isolated during a routine health assessment of wild largemouth bass (Micropterus salmoides) in Wisconsin in April of 2009. Further research is needed to determine the epidemiology and pathogenicity of the largemouth bass bunyavirus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Applied ergonomics research examines not only the fit, form and function of military uniforms, but also their ability to effectively camouflage personnel as they perform job-related tasks. Many of these job-related tasks involve moving through environments, but existing literature examining camouflage effectiveness often assumes that movement effectively "breaks" even the best camouflage patterns, rendering them of limited utility for reducing the visual signature of a moving target. However, recent research demonstrates that animals equipped with adaptive camouflage change their patterning in predictable ways during movement and this adaptation decreases detectability, suggesting that uniform patterning may still hold value for reducing conspicuity during movement. The present experiment examined whether three visual pattern characteristics, local contrast, orientation, and spatial frequency, would influence the detectability of a moving human target. Participants attempted to detect and localize a simulated human target moving across a background scene, and a factorial design varied target movement speed, and the local contrast, spatial frequency, and orientation of its camouflage patterning. Results showed that target detectability was strongly influenced by target movement rate, pattern local contrast, and pattern spatial frequency, and these effects persisted even under conditions of very fast movement. Importantly, we found that the effect of local contrast was most robust under conditions of movement, suggesting its importance for reducing detectability of moving personnel. We conclude that movement is not always sufficient to break the concealment offered by a pattern with low contrast and a spatial frequency match with its background. Results are discussed in the context of visual processing theories and the application of these findings to the design and development of static and adaptive camouflage patterns for military personnel., (Published by Elsevier Ltd.)

Traumatic injury is a leading cause of death and disability worldwide. Obesity may put trauma patients at risk for complications leading to negative clinical outcomes. Data on all hospital admissions due to traumatic injury in the Detroit metropolitan area between 2006 and 2014 were obtained from the Michigan State Inpatient Database. Generalized linear modelling was used to compare patients with and without obesity on three outcomes: mortality, length of hospital stay and total charges for care. Adjusting for demographics, patients with obesity had 26% longer hospitalization. Adjusting for demographics and length of stay, charges were 8% higher. Obesity was unrelated to mortality. Obesity had greater impact on length of stay among younger adults; its relationship with charges emerged only among older adults. Obesity has significant clinical implications for trauma care. Demands for trauma care resources, and the charges associated with providing care, are likely to increase as obesity rates rise., (© 2019 World Obesity Federation.)

Purpose/objectives: To determine neurocognitive and neurobehavioral impairment in long-term nasopharyngeal cancer survivors (NPC) treated with intensity-modulated radiotherapy (IMRT)., Materials/methods: A cross-sectional cohort of NPC ≥4 years (y) following IMRT was assessed. Objective cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and patient-reported memory was assessed with the MDASI-HN problems remembering item. Patient and family ratings of patients' neurobehavioral symptoms of apathy, disinhibition and executive dysfunction were assessed with the Frontal Systems Behavior Scale (FrSBe). Other patient-reported symptoms (MDASI-HN), mood (HADS), and quality of life (FACT-H&N) were also collected., Results: Among 102 participants: M:F = 66:36; median age 56y (32-77); median time since IMRT 7.5y (4.2-11.1). Impaired MoCA scores (<23) were observed in 33 (32%). Patient and family ratings of pre-illness neurobehavioral symptoms were in the normal range (total FrSBe T-scores 53.3 and 59.0 respectively). In contrast, post-treatment patient and family T-scores were clinically impaired (64.7, 71.3 respectively), with apathy, disinhibition and executive dysfunction post-treatment ratings all significantly worse than pre-treatment (p < 0.001). Prevalence of clinically significant post-treatment disturbance was high by patient and family ratings (48%/66% apathy, 35%/53% disinhibition, 39%/56% executive dysfunction). Post-treatment neurobehavioral symptoms strongly correlated with lower quality of life (r = -0.62) and higher anxiety (r = 0.62) and depression scores (r = 0.67, all p < 0.001). Total MoCA scores did not correlate with RT dose. However, greater declines in apathy, disinhibition and executive dysfunction were associated with receiving >75 Gy to temporal lobes., Conclusion: NPC treated with IMRT had moderate to high rates of neurocognitive impairment and clinically significant apathy, disinhibition, and executive dysfunction., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

There is a pressing need to develop tools for assessing possible neurotoxicity, particularly for chemicals where the mode of action is poorly understood. Tetrabromobisphenol A (TBBPA), a highly abundant brominated flame retardant, has lately been targeted for neurotoxicity analysis by concerned public health entities in the EU and USA because it is a suspected thyroid disruptor and neurotoxicant. In this study, infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) coupled to a Q Exactive Plus mass spectrometer was used for the analysis of neurotransmitters in the brains of rats exposed to TBBPA in gestation and lactation through their mothers. Three neurotransmitters of interest were studied in three selected regions of the brain: caudate putamen, substantia nigra (SN), and dorsal raphe. Stable isotope labeled (SIL) standards were used as internal standards and a means to achieve relative quantification. This study serves as a demonstration of a new application of IR-MALDESI, namely that neurotransmitter distributions can be confidently and rapidly imaged without derivatization.

Purpose: To assess the impact of the radiation therapy (RT) regimen and image guidance (image guided radiation therapy [IGRT]) protocol on local control (LC) for T2N0 glottic cancer treated with partial laryngeal intensity modulated radiation therapy (IMRT)., Methods and Materials: All patients with T2N0 glottic cancer treated with IMRT from 2006 to 2013 at a single institution were retrospectively reviewed. The gross tumor volume (GTV), delineated from endoscopic and/or radiologic findings, was expanded 0.5 cm for the high-dose clinical target volume and an additional 0.5 cm for the lower-dose clinical target volume (total of 1.0 cm from GTV). The planning target volume margin was 0.5 cm radially and 1 cm superiorly and inferiorly. RT regimens evolved from hypofractionated IMRT (RT-hypo, 60 Gy in 25 fractions over a period of 5 weeks) to moderately accelerated IMRT (RT-acc, 66-70 Gy in 33-35 fractions over a period of 5.5-6 weeks) since 2010. The IGRT matching surrogate changed from cervical vertebral bone (IGRT-bone) to laryngeal soft tissue (IGRT-larynx) in 2008. LC was compared between 3 sequential cohorts: RT-hypo/IGRT-bone, RT-hypo/IGRT-larynx, and RT-acc/IGRT-larynx. Multivariable analysis assessed the relative impact of RT regimen and IGRT technique on local failure separately., Results: Among 139 eligible patients (median follow-up period, 5.03 years [range, 0.8-10.5 years]), we identified 28 local, 6 regional, and 2 distant failures. A higher 3-year LC rate was observed for RT-acc/IGRT-larynx (89% [95% CI: 78%-95%]) versus RT-hypo/IGRT-larynx (80% [95% CI: 54%-91%]) and RT-hypo/IGRT-bone (70% [95% CI: 53%-80%]) (P = .02). Multivariable analysis adjusted for GTV (in cubic centimeters) and smoking status confirmed that IGRT-larynx versus IGRT-bone (hazard ratio, 0.40; P = .019) and RT-acc versus RT-hypo (hazard ratio, 0.34; P = .012) both reduced the risk of local failure., Conclusions: This single-institution cohort study shows a high LC rate (89%) for T2N0 glottic cancer following moderately accelerated partial laryngeal IMRT with daily laryngeal soft tissue matching IGRT. These results appear to represent an improvement attributable to changes in both IGRT matching and dose delivered, but their independent significance is unknown and further confirmation in a larger cohort is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Target visual salience and biological motion independently influence the accuracy and latency of observer detection. However, it is currently unknown how these target parameters might interact in modulating the detectability of camouflaged human targets. In two experiments, observers performed a visual target detection task. In a pilot experiment, observers detected a static human target with parametrically varied visual salience, superimposed on a complex background scene. As expected, results demonstrated varied target detectability as a function of salience, with observers showing higher hit rates and faster response times as a function of increased salience. In the Main Experiment, observers detected simulated human targets walking across a complex scene at five different speeds and three different levels of visual salience (as validated in the pilot experiment). We found strong effects of both movement rate and visual salience, and the two parameters interacted. Specifically, increasing the rate of biological motion increased detectability for even the least salient camouflage patterns. In other words, biological motion can "break" even the least conspicuous camouflage pattern. In contrast, a very salient pattern was highly detectable under static and moving conditions. Results are considered in relation to theories of camouflage detectability, and trade-offs between camouflage development efforts versus advanced training in military maneuvering., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: To report long-term (>4 years) toxicity and quality of life (QoL) among patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) in a nonendemic center., Methods and Materials: A cross-sectional cohort study enrolled patients with NPC who were disease-free and ≥4 years after IMRT ± chemotherapy. Physician-reported adverse events (Common Terminology Criteria for Adverse Events, version 4.03) and patient-reported QoL (Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue), utilities (EuroQOL-5D), head and neck symptoms (MD Anderson Symptom Inventory-Head and Neck), and emotional distress (Hospital Anxiety and Depression Scale) were collected. Consenting patients also underwent endocrine screening and audiometry., Results: Among 107 patients enrolled, median age at enrollment and time since treatment were 57 (32-81) and 7.5 years (4.2-11.1), respectively. Most patients (99%) received 70 Gy in 35 fractions; the majority (93%) received concurrent chemotherapy. Mean scores for the Functional Assessment of Cancer Therapy-Head and Neck, Functional Assessment of Chronic Illness Therapy-Fatigue, and EuroQOL-5D were 105.0 (46-148), 116.6 (44-160), and 0.85 (0.29-1.00), respectively. Dry mouth, mucus, swallowing/chewing, memory, and teeth/gum problems were scored highest on the MD Anderson Symptom Inventory-Head and Neck; mean symptom severity and symptom interference scores were 2.3 and 2.4, respectively. Grade 3 or higher physician-reported adverse events were noted in 50 patients (47%), most frequently hearing problems (46, 43%). Audiometry revealed significant bilateral hearing loss (grade ≥3) in 68 patients (72%). Depression (25%), anxiety (37%), and fatigue (28%) were common and strongly correlated with QoL. Most patients (69%) developed hypothyroidism; 1 patient (1%) developed pituitary dysfunction requiring hormone replacement. V50 >90 and V45 >99 to the thyroid correlated with significantly higher rates of hypothyroidism., Conclusions: Despite the implementation of IMRT, survivors of NPC still experience many physical symptoms that affect long-term QoL many years after treatment. Depression, anxiety, and fatigue remain common in long-term survivors and are highly correlated with QoL., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Objective: To compare local control (LC) in young women with early-stage breast cancer (BC) treated with hypofractionated (HF) whole breast irradiation (WBI) vs conventional fractionation (CF) following breast-conserving surgery (BCS)., Materials and Methods: Women <50 years with pT1-2N0 BC following BCS treated with WBI, CF (50Gy/25 fractions) or HF (42.4Gy/16 fractions) followed by a tumor bed boost (10-16Gy/5-8 fractions) from 2009 to 2013 were identified from an institutional database. Median follow-up was 5.2 years (range 0.3-8.4). Kaplan-Meier analysis was used to estimate 5-year LC. Logistic regression identified factors associated with receipt of CF vs HF WBI., Results: Of 270 eligible women, 227 (84%) were treated with HF and 43 (16%) with CF WBI. A tumor bed boost of 10 Gy/5 fractions was given in 97% of patients, 53% received adjuvant chemotherapy and 94% (225/239) with estrogen-positive disease received endocrine therapy. Median age was 45 years (range 30-49) in HF and 40 years (range 19-49) in the CF group. The 5-year LC rate was 99.3% (95% CI 97.9-100%, p = 0.495) in the HF and 97.5% (95% CI 92.8-100%) in the CF group. On univariate analysis, age ≤ 40 years or triple negative BC was associated with a decreased likelihood of receiving HF WBI. Only age remained significant on multivariate analysis [OR 2.82 (95% CI 1.45-5.48, p = 0.002)]., Conclusions: HF WBI was associated with excellent LC rates in this study cohort, comparable to CF WBI. However, CF WBI was more likely to be recommended to women <40 years., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Previous studies have investigated the anatomical distribution of para-aortic lymph nodes (PAN) in patients with cervical cancer. However, an atlas for accurate clinical target volume (CTV) delineation has yet to be defined. The purpose of this study was to design and verify a computerized tomography (CT) atlas to provide guidance for contouring the PAN CTV in patients with cervical cancer., Materials and Methods: This prospective study included 21 cervical cancer patients (design cohort) with 39 pathological PAN identified on (18)F-FDG PET-CT. PAN [left lateral para-aortic (LLPA), aorto-caval (AC), right para-caval (RPC) nodes] were delineated on CT simulation scans. Measurements were taken from the volumetric centre of the nodes to the edge of aorta and inferior vena-cava (IVC). Initially the aorta and IVC were expanded by the mean distance to the lymph node centre to create a CTV. Expansion margins were then increased asymmetrically until the CTV resulted in a clinically acceptable number of PAN included. The CTV was validated on a further 10 patients (validation cohort) with 29 PAN. A detailed contouring guide and accompanying visual atlas for elective PAN CTV delineation was created based on the validated margins., Results: For the design cohort (n = 21 patients, 39 PAN), the mean distance from the centre of the node to the aorta was 8 mm (range 4-17) for both LLPA (range 4-17) and AC (range 4-15) regions. Mean distance from the IVC to the centre of the nodes was 5 mm (range 4-6) in the RPC region and 6 mm (range 3-15) in the AC region. No PAN was superior to the T12-L1 interspace or the left renal vein or inferior to the L5-S1 interspace. For validation cohort (n = 10 patients, 29 PAN), mean distance from centre of the node to the aorta was 9 mm (range 5-15) in the LLPA region, 7 mm (range 6.5-14) in the AC region. Mean distance from the ICV to the centre of the nodes was 3 mm (range 2.5-4) in the RPC region and 5 mm (range 3-10) in the AC region. A CTV expansion from the aorta of 10 mm circumferentially and 15 mm laterally, and from the IVC of 8 mm anteromedially and 6 mm posterolaterally resulted in coverage of 97% (38/39) of PAN in the design cohort. On prospective validation, the described CTV included 97% (28/29) of PAN in the validation cohort., Conclusion: We propose the following PAN CTV; expansion from aorta of 10 mm circumferentially except 15 mm laterally, expansion from the IVC of 8 mm anteromedial and 6 mm posterolaterally. The suggested CTV includes 97% (28/29) PAN in a validated patient cohort. A detailed guide and accompanying visual atlas is provided to aid delineation of the PAN CTV in patients with cervical cancer., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Human observer test and evaluation of camouflage patterns is critical for understanding relative pattern conspicuity against a range of background scenes. However, very few validated methodologies exist for this purpose, and those that do carry several limitations. Five experiments examined whether masked priming with a dot probe could be used to reliably differentiate camouflage patterns. In each experiment, participants were primed with a camouflaged target appearing on the left or right of the screen, and then made a speeded response to a dot probe appearing on the same (congruent) or different (incongruent) side. Across experiments we parametrically varied prime duration between 35, 42, 49, 56, and 63 ms. Results demonstrated that as prime duration increased, a response time disadvantage for incongruent trials emerged with certain camouflage patterns. Interestingly, the most conspicuous patterns showed behavioral differences at a relatively brief (49 ms) prime duration, whereas behavioral differences were only found at longer prime durations for less conspicuous patterns; this overall results pattern matched that predicted by a visual salience model. Together, we demonstrate the viability of masked priming for the test and evaluation of camouflage patterns, and correlated outcomes for saliency models and primed object processing., (Published by Elsevier Ltd.)

Purpose: The purpose of this study was to evaluate the impact of the active breathing control (ABC) technique on IMN coverage and organs at risk in patients planned for postmastectomy radiation therapy (PMRT), with the inclusion of the internal mammary lymph nodes (IMNs). The effect of body mass index (BMI) on recorded dosimetric parameters was examined in the same patient cohort., Methods and Materials: Fifty left-sided postmastectomy patients with breast cancer who underwent free-breathing (FB) and ABC-Elekta CT simulation scans were selected at random from an institutional breast cancer database between 2008 and 2014. The ABC plans were directly compared with FB plans from the same patient., Results: The IMN planning target volume coverage met dosimetric criteria for coverage of receiving more than 90% of the prescribed dose (V90) >90%, although it decreased with ABC compared with FB (94.5% vs 98%, P < .001). Overall, ABC significantly reduced doses to all measured heart and left anterior descending coronary artery parameters, ipsilateral lung V20, and mean lung dose compared with FB (P < .001). There was no difference seen between the ABC and FB plans with respect to the dose to contralateral lung or contralateral breast. There was no correlation identified between BMI and any of the dosimetric parameters recorded from the ABC and FB plans., Conclusions: Our results suggest that ABC reduces IMN coverage in left-sided breast cancer patients planned for PMRT; however, dosimetric criteria for IMN coverage were still met, suggesting that this is not likely to be clinically significant. ABC led to significant sparing of organs at risk compared with FB conditions and was not affected by BMI. Collectively, the results support the use of ABC for breast cancer patients undergoing left-sided PMRT requiring regional nodal irradiation that includes the IMNs. Further prospective clinical studies are required to determine the impact of these results on late normal tissue effects., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Approaching disease elimination, it is crucial to be able to assess progress towards key objectives using quantitative tools. For Gambian human African trypanosomiasis (HAT), the ultimate goal is to stop transmission by 2030, while intermediary targets include elimination as a public health problem - defined as <1 new case per 10,000 inhabitants in 90% of foci, and <2000 reported cases by 2020. Using two independent mathematical models, this study assessed the achievability of these goals in the former Equateur province of the Democratic Republic of Congo, which historically had endemic levels of disease. The two deterministic models used different assumptions on disease progression, risk of infection and non-participation in screening, reflecting biological uncertainty. To validate the models a censor-fit-uncensor procedure was used to fit to health-zone level data from 2000 to 2012; initially the last six years were censored, then three and the final step utilised all data. The different model projections were used to evaluate the expected transmission and reporting for each health zone within each province under six intervention strategies using currently available tools. In 2012 there were 197 reported HAT cases in former Equateur reduced from 6828 in 2000, however this reflects lower active testing for HAT (1.3% of the population compared to 7.2%). Modelling results indicate that there are likely to be <300 reported cases in former Equateur in 2020 if screening continues at the mean level for 2000-2012 (6.2%), and <120 cases if vector control is introduced. Some health zones may fail to achieve <1 new case per 10,000 by 2020 without vector control, although most appear on track for this target using medical interventions alone. The full elimination goal will be harder to reach; between 39 and 54% of health zones analysed may have to improve their current medical-only strategy to stop transmission completely by 2030., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

This study identified and characterized Brucella species in the informal milk chain in Uganda. A total of 324 cattle bulk milk samples were screened for the genus Brucella by real-time PCR with primers targeting the bcsp31 gene and further characterized by the omp25 gene. Of the samples tested, 6.5% were positive for Brucella species. In the omp25 phylogeny, the study sequences were found to form a separate clade within the branch containing B. abortus sequences. The study shows that informally marketed cattle milk in Uganda is a likely risk factor for human brucellosis and confirms that B. abortus is present in the cattle population. This information is important for potential future control measures, such as vaccination of cattle., Competing Interests: and funding The authors have no conflict of interest to declare but acknowledge the SLU Global Food Security Research and Education Program 2010–2013 (UD40), the Ministry for Foreign Affairs, Sweden, for the financial support.

Pressure ulcers are common, increase patient morbidity and mortality, and costly for patients, their families, and the health care system. A retrospective study was conducted to evaluate the impact of pressure ulcers on short-term outcomes in United States inpatient populations and to identify patient characteristics associated with having 1 or more pressure ulcers. The US Nationwide Inpatient Sample (NIS) database was analyzed using the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis codes as the screening tool for all inpatient pressure ulcers recorded from 2008 to 2012. Patient demographics and comorbid conditions, as identified by ICD-9 code, were extracted, along with primary outcomes of length of stay (LOS), total hospital charge (TC), inhospital mortality, and discharge disposition. Continuous variables with normal distribution were expressed in terms of mean and standard deviation. Group comparisons were performed using t-test or ANOVA test. Continuous nonnormal distributed variables such as LOS and TC were expressed in terms of median, and nonparametric tests were used to compare the differences between groups. Categorical data were presented in terms of percentages of the number of cases within each group. Chi-squared tests were used to compare categorical data in different groups. For multivariate analysis, linear regressions (for continuous variable) and logistic regression (for categorical variables) were used to analyze the possible risk factors for the investigated outcomes of LOS, TC, inhospital mortality, and patient disposition. Coefficients were calculated with multivariate regression with all included patients versus patients with pressure ulcers alone. The 5-year average number of admitted patients with at least 1 pressure ulcer was determined to be 670 767 (average overall rate: 1.8%). Statistically significant differences between patients with and without pressure ulcers were observed for median LOS (7 days [mean 11.1 ± 15] compared to 3 days [mean 4.6 ± 6.8]) and median TC ($36 500 [mean $72 000 ± $122 900] compared to $17 200 [mean $32 200 ± $57 500]). The mortality rate in patients with a pressure ulcer was significantly higher than in patients without a pressure ulcer (9.1% versus 1.8%, OR = 5.08, CI: 5.03-5.1, P <0.001). Pressure ulcers were significantly more common in patients who were older or had malnutrition. The results of this study confirm the importance of prevention initiatives to help reduce the negative impact of pressure ulcers on patient outcomes and costs of care.

Background: Obesity is a global epidemic that has been increasing in prevalence. The only treatment method for durable weight loss is bariatric surgery. The aim of this study was to observe trends in usage and outcomes of bariatric operations used in the United States from 2008 to 2012., Methods: Analysis was performed on bariatric surgery admissions from 2008 to 2012 based off of the Nationwide Inpatient Sample database. Data were selected from using International Classification of Disease, 9th Revision codes correlating to bariatric procedures for the purpose of obesity. Annual estimates and trends were reviewed for patient demographics, procedure type, patient outcomes, and length of stay (LOS)., Results: A total of 598,756 bariatric procedures were examined. Laparoscopic gastric bypass was the most commonly used surgical method in 2008 (58.2%). A decreasing trend in its use, and the use of laparoscopic gastric banding (LGB), was equipoised with increasing use of laparoscopic sleeve gastrectomy (LSG). Use of LSG accounted for 8.2% of procedures in 2011 and 39.6% in 2012. LGB and LSG had the lowest rates of complications, in-hospital morbidity and mortality, and the shortest LOS whereas open bypass and duodenal switch had the highest rates of complications, in-hospital morbidity and mortality, and longest LOSs. Overall rates of venous thromboembolism increased from .08% in 2008 to .215% in 2012. Respiratory complications decreased from 6.1% to 3.9%. There were no observed trends in rates of renal complications, visceral injury, bleeding, and infections. In-hospital morbidity decreased, whereas mortality rates were stable at .1%., Conclusions: The utilization of bariatric procedures has reached a plateau in the United States. Changes in the composition of procedural types suggest that LSG has become a popular alternative to gastric bypass and LGB., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Recently, MIL-125(Ti) and NH2 -MIL-125(Ti), two titanium-based metal-organic frameworks, have attracted significant research attention in the field of photocatalysis for solar fuel generation. This work reveals that the differences between these structures are not only based on their light absorption range but also on the decay profile and topography of their excited states. In contrast to MIL-125(Ti), NH2 -MIL-125(Ti) shows markedly longer lifetimes of the charge-separated state, which improves photoconversion by the suppression of competing decay mechanisms. We used spectroelectrochemistry and ultrafast spectroscopy to demonstrate that upon photoexcitation in NH2 -MIL-125(Ti) the electron is located in the Ti-oxo clusters and the hole resides on the aminoterephthalate unit, specifically on the amino group. The results highlight the role of the amino group in NH2 -MIL-125(Ti), the electron donation of which extends the lifetime of the photoexcited state substantially., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The biology and behaviour of biting insects is a vitally important aspect in the spread of vector-borne diseases. This paper aims to determine, through the use of mathematical models, what effect incorporating vector senescence and realistic feeding patterns has on disease. A novel model is developed to enable the effects of age- and bite-structure to be examined in detail. This original PDE framework extends previous age-structured models into a further dimension to give a new insight into the role of vector biting and its interaction with vector mortality and spread of disease. Through the PDE model, the roles of the vector death and bite rates are examined in a way which is impossible under the traditional ODE formulation. It is demonstrated that incorporating more realistic functions for vector biting and mortality in a model may give rise to different dynamics than those seen under a more simple ODE formulation. The numerical results indicate that the efficacy of control methods that increase vector mortality may not be as great as predicted under a standard host-vector model, whereas other controls including treatment of humans may be more effective than previously thought., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Brucellosis is a key zoonosis of major public health, animal welfare and economic significance, and is endemic in livestock in Uganda. A cross-sectional epidemiological study was carried out to estimate the sero-prevalence of brucellosis and identify factors associated with sero-positivity in cattle in urban and peri-urban Gulu and Soroti towns of Northern and Eastern Uganda, respectively. A total of 1007 sera and data on biologically plausible risk factors from 166 herds and their spatial locations, were collected from cattle reared in urban and peri-urban Gulu and Soroti towns of Uganda. The sera were analyzed using indirect ELISA and sero-positive reactors confirmed by competitive ELISA. Multivariable models were used to investigate for risk factors. The overall animal-level and herd-level sero-prevalence was 7.5% (76/1007, 95% Confidence Interval (CI): 6.15-9.4%) and 27.1% (45/166, 95% CI: 20.9-34.3%), respectively. Herd-level sero-prevalence was significantly (P<0.001) higher in Soroti than Gulu. In Gulu town, sero-positivity increased with an increase in herd size (P=0.03) and age (P=0.002), and was higher in cattle brought in from western Uganda (P<0.0001). In Soroti town, introduction of new cattle into a herd was significantly (P=0.027) associated with herd sero-positivity. There was a geographically differential risk (clustering) of Brucella sero- positivity in herds in Soroti, while sero-positivity was homogeneously distributed in Gulu. The data highlight brucellosis occurrence and major risk factors for its transmission in cattle in urban and peri-urban areas.

Background: Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA., Materials and Methods: Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients)., Results: Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10-58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18-76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels., Discussion: In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens., (© 2013 International Hepato-Pancreato-Biliary Association.)

Modern infectious disease epidemiology has a strong history of using mathematics both for prediction and to gain a deeper understanding. However the study of infectious diseases is a highly interdisciplinary subject requiring insights from multiple disciplines, in particular a biological knowledge of the pathogen, a statistical description of the available data and a mathematical framework for prediction. Here we begin with the basic building blocks of infectious disease epidemiology--the SIS and SIR type models--before considering the progress that has been made over the recent decades and the challenges that lie ahead. Throughout we focus on the understanding that can be developed from relatively simple models, although accurate prediction will inevitably require far greater complexity beyond the scope of this review. In particular, we focus on three critical aspects of infectious disease models that we feel fundamentally shape their dynamics: heterogeneously structured populations, stochasticity and spatial structure. Throughout we relate the mathematical models and their results to a variety of real-world problems.

Ipilimumab is a fully human monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4 and has become the first immune checkpoint inhibitor to enter clinical practice, being recently approved for the treatment of metastatic melanoma. Immune toxicity due to ipilimumab causing colitis, hepatitis, dermatitis and hypophysitis is well-described. We report on a case of acute renal failure resolving rapidly with high-dose corticosteroid treatment highlighting the importance of vigilance for rarer immune-related toxicities as clinical experience with ipilimumab grows.

BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin's lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no 'B' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.

The ability to diagnose prostate carcinoma would be improved by the detection of a tumor-associated antigen. P504S, a cytoplasmic protein, was recently identified by cDNA library subtraction in conjunction with high throughput microarray screening from prostate carcinoma. The aim of this study was to establish the pattern of expression of P504S in prostate carcinoma and benign prostatic tissue. A total of 207 cases, including 137 cases of prostate carcinoma and 70 cases of benign prostate, from prostatectomies (n = 77), prostate needle biopsies (n = 112), and transurethral prostate resections (n = 18) were examined by immunocytochemistry for P504S. P504S showed strong cytoplasmic granular staining in 100% of prostate carcinomas regardless of Gleason scores and diffuse (>75% of tumor) staining in 92% of cases. In contrast, 171 of 194 (88%) of benign prostates, including 56 of 67 (84%) benign prostate cases and 115 of 127 (91%) cases of benign glands adjacent to cancers were negative for P504S. The remainders of benign prostates were focally and weakly positive for P504S. The staining pattern of these normal glands was different and easily distinguishable from that observed in prostate carcinoma. Expression of P504S was not found in basal cell hyperplasia, urothelial cells/metaplasia and small atrophic glands that may mimic prostate carcinoma. Our findings indicate that P504S is a highly sensitive and specific positive marker for prostate carcinoma.

No-glove, leather-glove, nitrile-glove, and vinyl-glove conditions were evaluated to determine their effects on grip strength and three-point pinch. Forty-one adult volunteers from a local university and local hospital participated in the two-day study. The order of testing was randomly assigned. A hydraulic hand dynamometer and a hydraulic pinch gauge were used to evaluate grip strength and three-point pinch with no glove and with each glove type. Grip strength and three-point pinch were tested on separate days. Grip strength test results showed statistically significant differences (p < 0.05) for no glove vs. leather glove, no glove vs. nitrile glove, no glove vs. vinyl glove, leather glove vs. nitrile glove, and leather glove vs. vinyl glove, but no statistically significant difference for nitrile glove vs. vinyl glove. Three-point pinch test results also showed statistically significant differences (p < 0.05) for no glove vs. leather glove, leather glove vs. nitrile glove, and leather glove vs. vinyl glove, but no statistically significant differences for no glove vs. nitrile glove, no glove vs. vinyl glove, and nitrile glove vs. vinyl glove. The results indicate that glove type may have clinical applications for occupational and physical therapists whose patients use gloves in the workplace.

Nearly all peptides generated by proteasomes during protein degradation are digested rapidly to amino acids, but a few proteasomal products escape this fate and are presented to the immune system on cell surface major histocompatibility complex class I molecules. To test whether these antigenic peptides may be inherently resistant to cytosolic peptidases, six different antigenic peptides were incubated with HeLa cell extracts. All six were degraded rapidly by a process involving o-phenanthroline-sensitive metallopeptidases. One antigenic peptide, FAPGNYPAL, was rapidly destroyed in the extracts by a bestatin-sensitive exopeptidase, apparently by the puromycin-sensitive aminopeptidase. The disappearance of the other five was reduced 30-90% by a specific inhibitor of the cytosolic endopeptidase, thimet oligopeptidase (TOP) (EC ), whose physiological function(s) have been unclear and controversial. All these peptides were sensitive to pure recombinant TOP. Furthermore, upon fractionation of the extracts, the major peptidase peak that degraded the ovalbumin-derived epitope, SIINFEKL, co-purified with TOP. In the extracts, TOP also catalyzed rapid degradation of N-extended variants of SIINFEKL and of other antigenic peptides, which in vivo can serve as precursors of these major histocompatibility complex-presented epitopes. This enzyme (unlike cell proteins that promote production of antigenic peptides) is not regulated by interferon-gamma. TOP seems to be primarily responsible for the rapid breakdown of antigenic peptides in cytosolic extracts, and our related studies (A. X. Y. Mo, K. Lemerise, W. Zeng, Y. Shen, C. R. Abraham, A. L. Goldberg, and K. L. Rock, submitted for publication) indicate that TOP by destroying such peptides limits antigen presentation in vivo.

Protein degradation by proteasomes is the source of most antigenic peptides presented on MHC class I molecules. To determine whether proteasomes generate these peptides directly or longer precursors, we developed new methods to measure the efficiency with which 26S and 20S particles, during degradation of a protein, generate the presented epitope or potential precursors. Breakdown of ovalbumin by the 26S and 20S proteasomes yielded the immunodominant peptide SIINFEKL, but produced primarily variants containing 1-7 additional N-terminal residues. Only 6-8% of the times that ovalbumin molecules were digested was a SIINFEKL or an N-extended version produced. Surprisingly, immunoproteasomes which contain the interferon-gamma-induced beta-subunits and are more efficient in antigen presentation, produced no more SIINFEKL than proteasomes. However, the immunoproteasomes released 2-4 times more of certain N-extended versions. These observations show that the changes in cleavage specificity of immunoproteasomes influence not only the C-terminus, but also the N-terminus of potential antigenic peptides, and suggest that most MHC-presented peptides result from N-terminal trimming of larger proteasome products by aminopeptidases (e.g. the interferon-gamma-induced enzyme leucine aminopeptidase).

The finding that MHC class I molecules are physically associated with the TAP transporter has suggested that peptides may be directly transported into the binding groove of the class I molecules rather than into the lumen of the endoplasmic reticulum (ER) where they subsequently would encounter class I molecules by diffusion. Such a mechanism would protect peptides from peptidases in the ER and/or escaping back into the cytoplasm. However, we find that an anti-peptide Ab that is cotranslationally transported into the ER prevents TAP-transported peptides from being presented on class I molecules. The Ab only blocks the binding of its cognate peptide (SIINFEKL) but not other peptides (KVVRFKDL, ASNENMETM, and FAPGNYPAL). Therefore, most TAP-transported peptides must diffuse through the lumen of the ER before binding stably to MHC class I molecules.