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A hierarchical production planning (HPP) and scheduling model is developed to solve a real-world problem in fibre manufacturing scheduling. The problem under study requires determining production sequences in the presence of variable setup costs in a multi-machine and multi-product environment. The concept of expected setup cost is developed to reduce the difficulty of addressing sequence-dependent setup costs at the aggregate level. A mixed integer linear programming model (MILP) incorporates the logic of expert systems to minimize the number and costs of machine setups and other associated costs. At the daily operational level, a set of heuristics is developed to manage contingencies, such as machine breakdowns and changes in demand. The heuristics effectively utilize idle capacity and inventories to smooth production and avoid unnecessary extra setups, therefore maintaining system stability. Data provided by the fibre plant is used to validate the model. Compared to the actual schedule, results from the model are more consistent with managerial priorities and substantial cost savings are obtained. [ABSTRACT FROM AUTHOR]

Production Switching Heuristics (PSH) have been suggested as realistic, practical alternatives to more sophisticated aggregate planning and scheduling models. A modified, two-level heuristic is presented and its properties investigated by use of the classical paint factory data (Linear Decision Rule). Even under relatively extreme circumstances, its cost performance is promising when compared with the LDR, LP and the original PSH. [ABSTRACT FROM AUTHOR]

The article appraises the observations and trends that have led to the conclusion that production management education is dying, as of 1974. Several observations are used as basis for the predicting the coming death of production management education, including the decline in the number of course offerings in the area of production management, decline in student interest as evidenced by decreasing enrollments in the production which still remain and the lack of management faculty interest in the field as evidenced by the death of production oriented publications in eminent management journals.

The special relationship between the dean and the head of an academic department is influenced by the college administrative organizational structure. The relationship between the academic dean and the department head has three aspects: (1) the social relationship; (2) the professional one-on-one relationship; and (3) the administrative team relationship. (JN)

This paper considers the problem of selecting matched pairs of observations for the reduction of bias in statistical hypothesis testing. A Euclidean distance function is suggested for measuring the similarity between paired observations. The matching process is then formulated initially as an assignment problem. Alternative formulations of the problem that would reduce computational difficulty are considered. [ABSTRACT FROM AUTHOR]

A hierarchical production planning model is developed for a forming facility of a major fibreglass manufacturer. The model establishes aggregate quarterly quantities for families of' products, monthly disaggregate production quantities for end-items within these families, and a weekly sequencing schedule of end-items. A key feature of the planning system is its ability to decompose total set-up cost into primary and secondary components and to account appropriately for each component at a distinct level of the planning hierarchy. The mathematical programming formulations, the accompanying solution algorithms, and the results of their application to nine months of actual company demand and cost data are presented. [ABSTRACT FROM AUTHOR]

Despite its ability to produce optimal solutions, the Linear Decision Rule (LDR) has not had a significant impact in the business environment. The Production Switching Heuristic (PSH), which has shown promising results when compared with the LDR, has experienced some business application because of its practicability and flexibility. During aggregate production planning, forecast errors are almost unavoidable, but the sensitivity of these models to such errors has not been thoroughly tested. Insufficient attention has been paid to truly understand the cost effects of forecast errors and other important interactions. The study investigates these issues by analyzing the results of 740 simulated problems. Using the famous "paint factory" cost data, the sensitivity of the LDR and the PSH are examined under various experimental conditions. The factors controlled at different levels are: forecast error mean, forecast error standard deviation, demand pattern, demand variability, and cost coefficients. The results show that 1) the PSH is generally less sensitive than the LDR to forecast errors, 2) both forecast error mean and standard deviation effectively measure the severity of forecast errors, and 3) underforecasts cause less cost penalty than overforecasts. The outcome of the study has helpful managerial implications for aggregate planning related decisionmaking. It suggests that the use of the PSH could result in potential cost savings even if significant forecast errors are envisioned as long as the period-to-period demand variability is not substantially high. Also, BIAS warrants more attention than MSE in evaluating the extent of forecast errors and their eventual cost impact on aggregate production planning. [ABSTRACT FROM AUTHOR]

Cholecystectomy is now being performed on an outpatient basis at many centers. The purpose of this study was to review the results of our large experience with this procedure. Between 1990 and 1997, 2288 patients underwent laparoscopic cholecystectomy at our clinic. A total of 847 (37%) were scheduled as outpatients. The selection criteria for planned outpatient laparoscopic cholecystectomy called for nonfrail patients with an ASA <4 who were living <2 h from the hospital. All patients received detailed preoperative instruction about outpatient laparoscopic cholecystectomy. A questionnaire was sent to 309 patients to sample their opinions. Since 1993, we have increased the number of planned outpatient cholecystectomies performed at our clinic, but the percentage of cholecystectomies completed on an outpatient basis has remained≈60%. A total of 547 of 847 operations scheduled as outpatient procedures (74.5%) were completed as planned, and 204 patients (24%) were kept in the hospital overnight. Twenty-seven (3%) were converted to open procedures. Eighteen laparoscopic patients (2%) stayed>1 day (range, 2–20). None of the patients died. Of the 142 patients (46%) who completed our opinion survey, 66% were happy with their experience, 32% would like to have stayed in the hospital, and 2% were undecided. Successful same-day surgery requires proper patient instruction, appropriate patient selection, and a low threshold to convert patients to inpatient status when the situation warrants. No major complications occurred as a result of same-day discharge, and two-thirds of the patients said that they preferred outpatient surgery. [ABSTRACT FROM AUTHOR]

Objective: Transcatheter arterial embolization (TAE) is a novel minimally invasive therapy for painful tendinopathy in patients with pain refractory to conservative management. The purpose of this study was to evaluate evidence on the efficacy of TAE for tendinopathy related pain., Materials and Methods: Using Embase, PubMed, and Web of Science, a systematic review and meta-analysis was performed to identify studies evaluating TAE for painful tendinopathy. The primary outcome measure was change in pain scale score at 6 months. A Ratio of Means (ROM) was used to compare the effect size post treatment as compared to baseline. The Visual Analog Scale (VAS) was used as the metric for comparison., Results: After screening titles, abstracts, and the full text, 5 studies met inclusion criteria. A total of 97 tendinopathy embolization procedures performed in 74 patients were included. Patients who underwent TAE demonstrated declines in VAS ROM at 1 day 0.53 [95% CI 0.31,0.88], 1 week (0.51 [95% CI 0.32,0.79]), 1 month (0.45 [95% CI 0.29, 0.71]), 3-4 months (0.33 [95% CI 0.22,0.48]), and 6 months following embolization (0.18[95% CI 0.13,0.26]), respectively., Discussion: TAE provides substantial short-term reductions in pain scores for patients suffering with refractory tendinopathy related pain of the rotator cuff, elbow extensor and flexor, Achilles, and patellar tendons., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Optimal diet and nutrition is vital for military readiness, performance and recovery. Previous research on military diets has primarily focused on the nutritional composition of field/combat rations and dietary intake during deployment. There is accumulating research exploring the usual free-living dietary intake and nutritional status of defence members in garrison (i.e. military bases on which personnel are stationed). However, no comprehensive review has been conducted to assess the overall dietary quality of defence members internationally. Therefore, this review assessed the diets of military populations against national nutritional guidelines and Military Dietary Reference Intakes (MDRI). A systematic literature review of original research was conducted. CINAHL, Medline (EBSCO), Scopus (Elsevier), PubMed and AMED databases were searched up to the 20/02/2023. A total of thirty-six studies met the inclusion criteria. The overall quality of included studies was high, with a low risk of bias. The diet quality scores indicate poor to fair diet quality among defence members. Defence members display low intakes of fruits, vegetables, wholegrains, seafood, plant protein and nuts and high intakes of added sugars, trans fat and processed meat. Results also indicated suboptimal intake of fibre, essential fatty acids, vitamin A, vitamin E, folate, Mg, Zn and iodine. This may lead to reduced performance, increased risk of chronic diseases and mental health disorders. More research is needed to assess the long-term consequences of poor diet quality in defence members. These results require the attention of policymakers to ensure that military education and food environment is supportive of healthy eating.

Purpose: Superior vena cava (SVC) syndrome is a constellation of symptoms that results from partial or complete SVC obstruction. Endovascular SVC stenting is an effective treatment for SVC syndrome with rapid clinical efficacy and low risk of complications. In this study, we assess the technical and clinical outcomes of a cohort of patients with SVC syndrome treated with the Abre TM self-expanding venous stent (Medtronic, Inc, Minneapolis, MN, USA)., Methods: An institutional database was used to retrospectively identify patients with SVC syndrome treated with Abre TM venous self-expanding stent placement between 2021-2023. Patient demographic data, technical outcomes, treatment effectiveness, and adverse events were obtained from the electronic medical record. Nineteen patients (mean age 58.6) were included in the study. Thirteen interventions were performed for malignant compression of the SVC, 5 for central venous catheter-related SVC stenosis, and 1 for HD fistula-related SVC stenosis refractory to angioplasty., Results: Primary patency was achieved in 93% of patients (17/19). Two patients (7%) required re-intervention with thrombolysis and angioplasty within 30 days post-stenting. Mean duration of clinical and imaging follow-up were 228.7 ± 52.7 and 258.7 ± 62.1 days, respectively. All patients with clinical follow-up experienced significant improvement in clinical symptoms post-intervention. No stent related complications were identified post-intervention., Conclusions: Treatment of SVC syndrome with the Abre TM self-expanding venous stent has high rates of technical and clinical success. No complications related to stent placement were identified in this study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Islets experience enormous stress during the isolation process, leading to suboptimal endocrine function after total pancreatectomy with islet autotransplantation (TPIAT). Our investigation focused on inducing isolation stress in islets ex vivo, where proinflammatory cytokines and hypoxia prompted the release of stress exosomes (exo S ) sized between 50 and 200 nm. Mass spectrometry analysis revealed 3 distinct subgroups of immunogenic proteins within these exo S : damage-associated molecular patterns (DAMPs), chaperones, and autoantigens. The involvement of endosomal-sorting complex required for transport proteins including ras-associated binding proteins7A, ras-associated binding protein GGTA, vacuolar protein sorting associated protein 45, vacuolar protein sorting associated protein 26B, and the tetraspanins CD9 and CD63, in exo S biogenesis was confirmed through immunoblotting. Next, we isolated similar exo S from the islet infusion bags of TPIAT recipients (N = 20). The exosomes from infusion bags exhibited higher DAMP (heat shock protein family A [Hsp70] member 1B and histone H2B) levels, particularly in the insulin-dependent TPIAT group. Additionally, elevated DAMP protein levels in islet infusion bag exosomes correlated with increased insulin requirements (P = .010) and higher hemoglobin A1c levels 1-year posttransplant. A deeper exploration into exo S functionality revealed their potential to activate monocytes via the toll-like receptor 3/7: DAMP axis. This stimulation resulted in the induction of inflammatory phenotypes marked by increased levels of CD68, CD80, inducible nitric oxide synthase, and cyclooxygenase-2. This activation mechanism may impact the successful engraftment of transplanted islets., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Issue Addressed: This cross-sectional analysis of the Australian 3D study aimed to determine the prevalence of psychological distress and describe its associated characteristics in adults recently diagnosed with type 2 diabetes., Methods: Adults (aged 18 years and over) who were recently diagnosed with type 2 diabetes (<6 months prior) were recruited through the Australian National Diabetes Services Scheme in 2018-2019. Demographic and health data were collected via interview-administered telephone surveys. Hierarchical regression was used to analyse whether demographic, self-care and clinical characteristics were associated with psychological distress, as measured by the K10 questionnaire., Results: Of the participants (n = 223), 26.3% presented with psychological distress, with 8.4% reporting mild, 8.4% reporting moderate and 9.5% reporting severe psychological distress. Neither age, sex, body mass index or taking anti-depressant medications were associated with the presence of psychological distress (p > .05). Being a smoker, living situation, less physical activity and poorer healthy eating beliefs and intentions were significantly associated with psychological distress in those not taking anti-depressant medications (p < .05). Being female was significantly associated with psychological distress in those taking anti-depressant medications (p < .05)., Conclusion: The study found that psychological distress is highly prevalent in adults recently diagnosed with type 2 diabetes. Behavioural factors such as smoking and low physical activity, as well as psycho-social factors such as living situation, poor healthy eating beliefs and intentions were significantly associated with psychological distress. This has implications for the management of people with newly diagnosed type 2 diabetes. SO WHAT?: Psychological distress is highly prevalent in Australian adults newly diagnosed with type 2 diabetes, emphasising the urgent need for enhanced psychological care to support this group., (© 2023 The Authors. Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.)

Background: Relationship-based, whole person care is foundational to quality general practice. Previous research has identified several characteristics of deep General Practitioner (GP)-patient relationships and their association with improved patient concordance, satisfaction and perceived health outcomes. Psychological attachment theory has been used to understand therapeutic relationships, but has only been explored to a limited extent in the general practice context. Additionally, evolving changes in sociocultural and commercial practice contexts may threaten relationship-based care. In view of this, we aimed to explore the nature and experience of deep GP-patient relationships, as identified by patients, from GP and patient perspectives., Methods: Semi-structured interview design. An initial survey assessed patients' perceived depth of their relationship with their GP, using the Health Care Provider Attachment Figure Survey and Patient-Doctor Depth of Relationship Scale. Patients who reported a deep relationship, and their GPs, were purposively selected for individual interviews exploring their experience of these relationships. A post-interview survey assessed interviewees' attachment styles, using the Modified and Brief Experiences in Close Relationships Scale. Patient interviewees also rated the patient-centredness of their GP's clinic using the Person-Centred Primary Care Measure. Transcripts were analysed using thematic analysis., Results: Thirteen patients and five GPs were interviewed. Four themes characterised deep relationships: the 'professional'; human connection; trust; and 'above and beyond'. Patient, GP and practice team all contributed to their cultivation., Conclusions: We present a revised conceptual framework of deep GP-patient relationships. Deep relationships come to the fore in times of patient trouble. Like attachment relationships, they provide a sense of safety, caring and support for patients experiencing vulnerability. They can stretch GP boundaries and capacity for self-care, but also provide joy and vocational satisfaction. Patients may not always desire or need deep relationships with their GP. However, findings highlight the importance of enabling and cultivating these for times of patient hardship, and challenges of doing so within current healthcare climates., (© 2023. The Author(s).)

Purpose: Evaluate physicians who treat musculoskeletal (MSK) disorders in their knowledge of image-guided MSK interventions, and identify areas that could benefit from education., Materials and Methods: A 17-question survey was distributed to orthopaedic surgeons, physiatrists, and rheumatologists in the 14-hospital health system. It inquired about demographics, practice environment, awareness of interventional radiology (IR) and MSK radiology (MSKR) training, referral patterns, and knowledge of image-guided MSK interventions., Results: In total, 59 of 303 physicians completed the survey (41% orthopaedists, 35% physiatrists, and 24% rheumatologists). Most (93%) were attendings and 41% were female. A minority of survey respondents (17%) recognized the designation of IR as a distinct specialty of medicine per the American Board of Medical Specialties, in contrast to MSKR, which is not designated as a distinct specialty. When queried about IR procedures not under investigation, 24% selected genicular artery embolization and 31% selected embolization for adhesive capsulitis. Barriers to referral were as follows: 21% of specialists performed the procedure, 17% listed electronic medical record challenges, 14% reported scheduling difficulty, 13% reported no barriers, 11% reported difficulty consulting, 11% referred to another specialty, 10% did not have enough knowledge of image guided procedures, and 3% reported the procedure is not performed by IR or MSKR., Conclusions: Survey data reveal a knowledge gap among surveyed physicians regarding IR as a specialty as well as areas of IR research in MSK disorders. Findings suggest areas where referring physicians can be educated and identify barriers to referral., Competing Interests: Declaration of competing interest The authors have no competing interests to report for this study., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Genicular artery embolization (GAE) is a minimally invasive therapy for symptomatic osteoarthritis (OA) in patients with knee pain refractory to conservative management. The purpose of this study was to evaluate evidence on the effectiveness of GAE for OA related knee pain as part of a systematic review and meta-analysis., Materials and Methods: Using Embase, PubMed, and Web of Science, a systematic review was performed to identify studies evaluating treatment of knee OA with GAE. The primary outcome measure was change in pain scale score at 6 months. A Hedge's g was computed as a measure of effect size, selecting Visual Analog Scale (VAS) first if available and Knee Injury and Osteoarthritis Outcome Score and Western Ontario and McMaster Universities Osteoarthritis Index if VAS was not available., Results: After screening titles, abstracts, and the full text, 10 studies met inclusion criteria. A total of 351 treated knees were included. Patients who underwent GAE demonstrated declines in VAS pain scores at 1 month {- 34 points [95% CI (- 43.8, - 24.6)], 3 months {- 30 points [95% CI (- 41.7, - 19.2)], 6 months {- 41 points [95% CI (- 54.0, - 27.2)], and 12 months {- 37 points [95% CI (- 55.0, - 18.1)]. Hedges' g from baseline to 1, 3, 6, and 12 months, was {- 1.3 [95% CI (- 1.6, - 0.97)]}, {- 1.2 [95% CI (- 1.54, - 0.84)]}, {- 1.4 [95% CI (- 2.1, - 0.8)]}, and {- 1.25 [95% CI (- 2.0, - 0.6)]}, respectively., Conclusion: GAE provides durable reductions in pain scores for patients suffering with mild, moderate, and severe OA., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Background: Diet quality plays an important role in the prevention of diabetes-related complications in people with type 2 diabetes mellitus (T2DM). However, evidence is scarce on how diet quality typically changes over time after diagnosis. The present study aimed to describe how the diet quality of individuals newly diagnosed with T2DM changes over a 12-month period and to identify factors associated with diet quality changes., Methods: A 12-month prospective, observational case-series study was undertaken. Two-hundred and twenty-five Australian adults (56% men) newly diagnosed with T2DM were recruited from the Diabetes Australia national database. Participants completed five interviewer-administered surveys over 12 months: baseline, 3, 6, 9 and 12 months. Demographic, physical and health characteristics, and dietary intake data were collected at each timepoint. Diet quality was assessed using the Dietary Approaches to Stop Hypertension (DASH) scoring tool. To assess changes in DASH, energy, fruit and vegetable intake over time, repeated measure analyses of variance were used. Multivariate repeated measures models investigated characteristics associated with these dietary changes., Results: The mean DASH score of the sample remained stable at 24.0 across the 12 months. Very few participants (6.8%) improved diet quality consistently across the study period. No associations between DASH, energy, fruit or vegetable intake over time and characteristics were observed., Conclusions: This observational study suggests that without dedicated interventions (the natural course), most people newly diagnosed with T2DM will not achieve meaningful diet quality change. The development of cost-effective interventions to achieve sustained diet quality change early after diagnosis are warranted., (© 2021 The British Dietetic Association Ltd.)

Objectives: Excessive fecal bile acids in adults have been associated with diarrhea-predominant irritable bowel syndrome (IBS-D), but their role in pediatric IBS-D is unknown. Serum markers including 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor-19 (FGF-19) were validated in adults to detect bile acid diarrhea (BAD) compared to 48-hour fecal bile acid collection (48FBA). Our aims were to assess fasting serum C4 and FGF-19 and 48FBA in a pediatric population, to compare measurements in IBS-D patients and healthy controls (HC), and to determine the prevalence of BAD among children with IBS-D., Methods: Using a cross-sectional design, 26 patients with IBS-D and 56 HC were recruited in two pediatric tertiary care centers. Fasting serum C4 and FGF-19 and 48FBA were obtained. Participants completed a 7-day bowel diary coinciding with stool collection. Associations were analyzed using Spearman correlations., Results: Mean age was 14.7 ± 2.5 years (42.3% female) in IBS-D and 12.6 ± 2.4 years (39.3% female) in HC. There was a significant correlation of C4 with 48FBA (r = 0.48, P < 0.05) and an inverse association with FGF-19 (r = -0.43, P < 0.05). No significant differences were noted in C4 (P = 0.32), FGF-19 (P = 0.1), or 48FBA (P = 0.5) between IBS-D and HC groups; however, 20% of IBS-D patients had elevated C4 and 28% had low FGF-19 values.Fecal primary BA was significantly correlated with stool frequency (r = 0.45, P < 0.002)., Conclusions: Correlations of C4 with 48FBA and FGF-19 are confirmed in a pediatric population. Twenty percent of pediatric patients with IBS-D had abnormal fasting serum C4. This serum test could be applied to identify BAD in pediatric IBS-D., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Prediabetes increases the risk of developing type 2 diabetes (T2D). Improving diet quality is key in preventing this progression, yet little is known about the characteristics of individuals with prediabetes or the nutrition care they receive., Objectives: This study aims to identify characteristics and experiences associated with receiving a prediabetes diagnosis prior to developing T2D., Methods: A mixed methods study encompassed a quantitative subanalysis of participants with newly diagnosed T2D from The 3D Study, and semi-structured telephone interviews with a subsample of participants who were previously diagnosed with prediabetes. Interviews were thematically analysed and survey data synthesized using SPSS statistical software., Results: Of the 225 study participants, 100 individuals were previously diagnosed with prediabetes and 120 participants were not. Those with prediabetes were less likely to be smokers (P = 0.022) and more likely to be satisfied with seeing a dietitian (P = 0.031) than those without a previous prediabetes diagnosis. A total of 20 participants completed semi-structured interviews. Thematic analysis revealed three themes: (i) experiencing a prediabetes diagnosis; (ii) receiving nutrition care during prediabetes and (iii) reflecting on the experience of receiving care for prediabetes versus T2D., Conclusions: There are gaps in the current management of prediabetes in Australia. Low rates of prediabetes diagnosis and an ambiguous experience of receiving this diagnosis suggest an area of health service improvement. With no difference in diet quality between individuals with and without a previous prediabetes diagnosis, the nutrition care during prediabetes may be more important than the diagnosis itself in delaying the onset of T2D., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Background: Dietary intake impacts glycaemic control through its effect on weight and glucose-insulin homeostasis. Early glycaemic control is associated with improved outcomes and reduced mortality for people with type 2 diabetes (T2D). To date, the diet quality of people with T2D has only been studied cross-sectionally. The objective of this paper is to quantify short-term improvements in diet quality and to identify factors associated with improvements after T2D diagnosis among participants in the 3D study., Methods: This paper presents data from the 3D study of 225 Australian adults, newly diagnosed with T2D. Telephone interviews collected demographic, diet, physical and health data at baseline and 3 months. Diet quality was assessed using the Dietary Approaches to Stop Hypertension (DASH) tool to examine short-term changes in diet quality after diagnosis. Participants were categorised into two groups: those who improved their diet quality by 3 months (increase in DASH score of 3 or more) and those who did not. Factors associated with change in DASH scores were clinically and statistically evaluated., Results: The 3D cohort was comparable to Australian cohorts with diabetes by gender and body mass index (BMI) but differed by age, remoteness and socioeconomic status. Mean (SD) baseline DASH score was 24.4 (4.7), in the midrange of possible scores between 8 and 40. One third of participants improved their DASH score by 3-months. This group had lower diet quality (p < 0.001), lower BMI (p = 0.045), higher physical activity levels (p = 0.028) and were less likely to smoke (p = 0.018) at baseline., Conclusions: Diet quality changes after diagnosis do not appear to be associated with demographic characteristics but were associated with lifestyle behaviours. Strategies targeted at better supporting smokers, those with low physical activity and higher BMI are required. Future research should investigate how the diet quality changes people make around time of diagnosis are related to long-term health outcomes.

Objectives: Individual understanding of and expectations for chronic pain treatment can influence treatment adherence and thus success, but little is known about these critical factors in parents and children presenting with pain-predominant functional gastrointestinal disorders. The aim of this study was to identify parent and patient understanding of pain-predominant functional gastrointestinal disorders, expectations for treatment, and interventions utilized before presenting to a multidisciplinary clinic., Materials and Methods: This was a prospective study of patients evaluated in a Multidisciplinary Functional Abdominal Pain Program. Before the clinic visit, parents and patients completed questionnaires regarding their understanding of chronic pain, perceptions of abdominal pain contributors, expectations regarding treatment, and identification of previous interventions utilized., Results: Participants were knowledgeable regarding the biology of chronic pain. Perceptions of contributors to abdominal pain included a sensitive stomach, general stress, and nerves/worry. Most had attempted to treat their pain with medication, exercise or physical therapy, or a psychological treatment. Participants reported that receiving a definite diagnosis would be the most helpful intervention, followed by psychological treatment., Discussion: Participants were knowledgeable regarding chronic pain, but still indicated that receiving a definite diagnosis would be the most helpful intervention. Most had tried multiple interventions and did not believe that further medication, testing, or surgery would solve their pain. Instead, parents presenting at this Functional Abdominal Pain Program appeared most hopeful about the benefits of multidisciplinary treatment approaches including psychological interventions, a focus on activity and functioning, and complementary and alternative medicine interventions.

Objective: To determine whether clinical and patient-reported outcomes differ in children receiving blenderized diets compared with conventional formula., Study Design: We conducted a prospective cohort study of 70 children aged 1-18 years receiving blenderized diets vs conventional formula via feeding tube. We assessed rates of hospitalization and visits to the emergency department (ED) at Boston Children's Hospital in 2017 and Likert scale addressing satisfaction with feeding regimen; Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire; Pediatric Quality of Life Inventory; and Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scale., Results: Participants receiving blenderized diets (n = 42, 60%) did not differ in demographics or comorbid diagnoses from those receiving conventional formula (n = 28, 40%). Rates of total visits to the ED (0.8 ± 1.5 vs 1.4 ± 2.7, P = .05), total admissions (0.8 ± 1.2 vs 1.7 ± 2.3, P = .01), and respiratory-related admissions (0.2 ± 0.5 vs 0.6 ± 0.8, P = .04) per year were significantly lower in participants receiving blenderized diets, and respiratory-related visits to the ED trended toward significance (0.1 ± 0.4 vs 0.4 ± 0.8, P = .08). Compared with those receiving conventional formula, participants on blenderized diets reported greater satisfaction ratings (Likert scale 4.3 ± 1.0 vs 3.3 ± 1.2, P = .001), lower symptom (0.7 ± 0.8 vs 1.2 ± 1.1, P = .03), and total (0.8 ± 0.8 vs 1.2 ± 1.0, P = .02) scores on Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire and greater scores on the Pediatric Quality of Life Inventory Gastrointestinal Symptoms Scale, indicating less nausea and vomiting (64.0 ± 22.6 vs 49.0 ± 37.9, P = .02), abdominal pain (65.0 ± 26.8 vs 56.4 ± 33.9, P = .04), diarrhea (87.9 ± 15.5 vs 73.6 ± 26.3, P = .004), and fewer total symptoms (70.2 ± 16.3 vs 62.3 ± 19.6, P = .03)., Conclusions: Blenderized diets are associated with decreased healthcare use, improved symptom scores, and increased patient satisfaction compared with conventional formulas., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Given the heightened interest in manipulation of co-signaling cascades for cancer immunotherapy, we sought to determine how/whether tumors decorated with therapeutic monoclonal antibodies (mAbs) impact the expression of co-signaling molecules on human NK cells. Stimulation of NK cells with aggregated IgG1 resulted in the upregulation of HAVCR2 - the gene encoding T-cell immunoglobulin and mucin-containing domain (Tim)-3 - known to be involved in the induction of peripheral T cell tolerance. This upregulation of HAVCR2 was recapitulated at the protein level, following NK cell stimulation by either mAb opsonized tumors, recombinant human IgG1 Fc multimer, and/or non-Fc stimuli e.g. IL-12/IL-18. The patterns of Tim-3 expression were temporally distinct from the FcR mediated induction of the co-signaling molecule, 4-1BB (CD137), with Tim-3 increases observed twenty minutes following exposure to Fc multimers and remaining at high levels for at least six hours, while increases in CD137 expression were first observed at the four-hour time point. Importantly, these Tim-3+ NK cells were functionally diverse, as evidenced by the fact that their ability to produce IFN-γ in response to an NK cell responsive tumor was strictly dependent upon the stimuli employed for Tim-3 induction. These data suggest that Tim-3 upregulation is the common end-result of NK cell activation by a variety of unique and overlapping stimuli and is not an independent marker of NK cell exhaustion. Furthermore, our observations potentially explain the diverse functionality attributed to Tim-3+ NK cells and should be considered prior to use of anti-Tim-3 inhibitory mAbs for cancer immunotherapy., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Functional gastrointestinal disorders (FGIDs) are common in children and adolescents, frequently resulting in extensive testing, school absenteeism, disability, and poor quality of life. 1-3 FGIDs result from a complex interplay between genetic predisposition, biological triggers, and psychosocial triggers, and are best explained by the biopsychosocial model. 1 Although this implies the necessity of multidisciplinary treatment, studies showing the efficacy of such an intervention are lacking. We describe the outcome of children with severe FGIDs treated in a multidisciplinary program., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: mAb114 is a single monoclonal antibody that targets the receptor-binding domain of Ebola virus glycoprotein, which prevents mortality in rhesus macaques treated after lethal challenge with Zaire ebolavirus. Here we present expedited data from VRC 608, a phase 1 study to evaluate mAb114 safety, tolerability, pharmacokinetics, and immunogenicity., Methods: In this phase 1, dose-escalation study (VRC 608), conducted at the US National Institutes of Health (NIH) Clinical Center (Bethesda, MD, USA), healthy adults aged 18-60 years were sequentially enrolled into three mAb114 dose groups of 5 mg/kg, 25 mg/kg, and 50 mg/kg. The drug was given to participants intravenously over 30 min, and participants were followed for 24 weeks. Participants were only enrolled into increased dosing groups after interim safety assessments. Our primary endpoints were safety and tolerability, with pharmacokinetic and anti-drug antibody assessments as secondary endpoints. We assessed safety and tolerability in all participants who received study drug by monitoring clinical laboratory data and self-report and direct clinician assessment of prespecified infusion-site symptoms 3 days after infusion and systemic symptoms 7 days after infusion. Unsolicited adverse events were recorded for 28 days. Pharmacokinetic and anti-drug antibody assessments were completed in participants with at least 56 days of data. This trial is registered with ClinicalTrials.gov, number NCT03478891, and is active but no longer recruiting., Findings: Between May 16, and Sept 27, 2018, 19 eligible individuals were enrolled. One (5%) participant was not infused because intravenous access was not adequate. Of 18 (95%) remaining participants, three (17%) were assigned to the 5 mg/kg group, five (28%) to the 25 mg/kg group, and ten (55%) to the 50 mg/kg group, each of whom received a single infusion of mAb114 at their assigned dose. All infusions were well tolerated and completed over 30-37 min with no infusion reactions or rate adjustments. All participants who received the study drug completed the safety assessment of local and systemic reactogenicity. No participants reported infusion-site symptoms. Systemic symptoms were all mild and present only in four (22%) of 18 participants across all dosing groups. No unsolicited adverse events occurred related to mAb114 and one serious adverse event occurred that was unrelated to mAb114. mAb114 has linear pharmacokinetics and a half-life of 24·2 days (standard error of measurement 0·2) with no evidence of anti-drug antibody development., Interpretation: mAb114 was well tolerated, showed linear pharmacokinetics, and was easily and rapidly infused, making it an attractive and deployable option for treatment in outbreak settings., Funding: Vaccine Research Center, US National Institute of Allergy and Infectious Diseases, and NIH., (Copyright © 2019 Elsevier Ltd. All rights reserved.)