bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ranking Operational Causes of Bullwhip Effect in Supply Chain Using AHP: Perception of Managers in FMCG Sector
Authors: Khan Maaz Hasan , Ahmad Salma 
Published: September 2018

Bullwhip effect (BWE), which refers to the phenomenon wherein the variance in demand orders increases as one moves up the supply chain (SC), has been a source of concern for most of the SC managers as it has serious implications in the SC. Problems can vary from inefficient ordering and inventory policies (IP) to higher total cost of SC with extreme cases of stock-out and disruptions in the SC. The literature on this topic suggests various factors which cause BWE and these have further been divided into two broad groups, namely, “operational causes” and “behavioural causes.” This study focuses on the operational factors identified through the survey of literature from 1990 to 2013 and suggests 18 factors which contribute to the BWE. Further, from an analysis of literature, based on a number of articles and their citations, and responses from field experts through a questionnaire, a refined list of seven factors has been taken up for the study. These factors have been ranked using the “analytical hierarchy process” (AHP). The ranking is based on pairwise comparisons based on the perception of the SC managers in the manufacturing sector in north India. The article is divided into five sections. The first section deals with the introduction and identification of the BWE. The second section identifies the various factors which cause this effect under the two broad categories, namely, the operational and behavioural factors. The third section discusses AHP and the methodology used in the article to rank the operational factors. The fourth section presents the results in a tabular and graphical form. Order batching (OB) is found to be the biggest contributor of BWE in manufacturing sector in the aforementioned region followed by demand signal processing (DSP), lead time (LT), IP, price fluctuation (PF), lack of trust (LOT), and number of echelons (NOE). The fifth and final section undertakes a discussion and presents guidelines for future research.
Rural and Agricultural Employment Conundrum
Authors: Deshpande R. S. , Subramanian S. 
Published: September 2018

The changing employment scenario is opening a few puzzles. While cultivators are declining, the number of operational holding is increasing very fast. Similarly, agricultural labourers are increasing but farmers indicate almost unanimously non-availability of farm labour. Age cohorts’ analysis indicates increasing average age of cultivators for future too. The central theme of this article is to bring forth this dual puzzle and decipher the changes. Our attempt here is to highlight three issues, namely, disappearing cultivators, increasing non-cultivating holdings and increasing farmers’ average age. Besides, even with increasing number of agricultural labourers, farmers indicate non-availability of farm hands. These posers are highlighted with the help of Census data data. JEL: J08, J18, J21
Placental Histology After Minor Trauma in Pregnancy: A Pilot Study
Authors: van der Knoop BJ , van der Voorn JP , Nikkels PGJ , Zonnenberg IA , van Weissenbruch MM , Vermeulen RJ , de Vries JIP 
Published: September 2018

Objective Trauma in pregnancy may cause placental abruption. Consequences of moderate placental injury on neurodevelopment are unknown. The aim was to evaluate placental histology after maternal trauma. Methods A prospective study was conducted at 2 tertiary medical centers in the Netherlands. Placentas from women exposed to maternal trauma ≥ 20 weeks’ gestational age were histologically examined. Neurological follow-up of the infants was performed at 1 year of age by means of Alberta Infant Motor Scale. Histological findings were compared to placentas from pregnancies without trauma. Principal Results Thirteen placentas were investigated in the trauma group. The control group consisted of 15 placentas. Placental pathology was seen more often in the trauma cases (11 of the 13) than in the controls (6 of the 15), P = .024. Neurological follow-up was normal. Conclusions In this small population, majority of the placentas showed pathology after minor trauma in pregnancy without consequences for neurodevelopment at 1 year.
Dislocation of large-diameter head metal-on-metal total hip arthroplasty and hip resurfacing arthroplasty
Authors: Miettinen Simo S A , Mäkinen Tatu J , Laaksonen Inari , Mäkelä Keijo , Huhtala Heini , Kettunen Jukka S , Remes Ville 
Published: September 2018

Introduction: Dislocation of large-diameter head (LDH) metal-on-metal (MoM) total hip arthroplasty (THA) or hip resurfacing arthroplasty (HRA) is a rare complication. This study aimed to determine the incidence and risk factors for dislocation of LDH MoM THAs and HRAs. Methods: This retrospective analysis considered 4038 cementless LDH MoM THAs and HRAs, 3207 THAs in 2912 patients and 831 HRAs in 757 patients. The end of follow-up was revision due to dislocation. Incidence of dislocation was evaluated from this study population of 4038, and study groups were formed. The study was designed as a case-control study, and a threefold stratified randomised control group was formed. Demographic data were collected and radiological analyses were performed in the study groups. Results: There were 26/3207 (0.8%) early dislocations in the THA group, and 6/831 (0.7%) in the HRA group ( p = 0.9). Most LDH THA dislocations occurred in a group with head size ⩽ 38 mm (18/26) ( p < 0.001). In dislocated hips, there were more dysplastic acetabula and post-traumatic hips than in the control group ( p = 0.036). In the dislocation group, the mean acetabulum component anteversion angle was 19.6° (standard deviation [SD] 13.4°) and in the control group it was 23.2° (SD 10.4°) ( p = 0.006); 7/32 (21.8%) of dislocated THAs needed revision surgery, and mean time to revision from the index surgery was 1.2 (SD 2.6) years. Discussion: Dislocations occurred more often in THAs of head size ⩽ 38 mm and with a smaller anteversion angle of the acetabulum component. Hip dysplasia and post-traumatic osteoarthritis were more common in patients with dislocation.
“It’s a disease of families”: Neurologists’ insights on how to improve communication and quality of life for families of Parkinson’s disease patients
Authors: Schwartz Rachel , Zulman Donna , Gray Caroline , Goldstein Mary K , Trivedi Ranak 
Published: September 2018

Objectives Parkinson’s disease presents an evolving challenge for patients and families due to an unpredictable disease trajectory and symptoms that complicate social interactions. In this study, we explore neurologists’ perspectives on the challenges Parkinson’s disease presents for families and the strategies they use to improve communication and quality of life. Methods We conducted hour-long semi-structured interviews with 16 neurologists at 4 care delivery institutions in the San Francisco Bay Area, focusing on techniques neurologists use to support families through the Parkinson’s disease journey. Results Neurologists identified strategies for addressing caregiver–patient disagreements around symptom accuracy and negotiating driving safety. Family education is needed to contextualize patient symptoms and to identify psychosocial support resources. Unmet caregiver needs remain, particularly in the form of psychosocial support, respite care and support for unequal gender dynamics in the Parkinson’s disease caregiving experience. Discussion Family members of Parkinson’s disease patients face unique caregiving and interpersonal challenges due to the nature of the disease. Targeted education and structural support are needed to alleviate current burdens and allow for improved patient- and family-centered care.
An evidence-based review of enhanced recovery after surgery in total knee replacement surgery
Authors: Ghosh Arijit , Chatterji Urjit 
Published: September 2018

Rationale: Enhanced recovery after surgery is gaining popularity among orthopaedic surgeons across the globe and hence a strong evidence base had to be reviewed to make an evidence-based sustainable protocol. Methods The following databases, PubMed, OVID, Cochrane database and EMBASE were searched. The search was limited to 15 components of enhanced recovery after surgery programme which is divided into preoperative, intraoperative and postoperative phases. Inclusion criteria were restricted to articles published in English within the last 15 years and articles comprising of unicompartmental arthroplasty, revision knee arthroplasty, bilateral simultaneous knee arthroplasty and only hip arthroplasty excluded. The full texts were analysed and controversies and limitations of various studies were summarised. Discussion Each component of the programme was thoroughly reviewed and strength and weaknesses of the evidence base summarised. The strength of the evidence was assessed by critically appraising the study methodology and justifying the appropriateness of the inclusion in enhanced recovery after surgery protocol. Conclusion Enhanced recovery after surgery has already been used successfully in various surgical specialities. Enhanced recovery after surgery programmes in knee arthroplasty are yet to be established as a universal practice to be adopted globally. This evidence-based review provides an insight into the best evidence linked to each component and their rationale for inclusion in the proposed enhanced recovery after surgery protocol.
Risks for lymphoma and gastrointestinal carcinoma in patients with newly diagnosed adult‐onset celiac disease: Consequences for follow‐up
Authors: van Gils Tom , Nijeboer Petula , Overbeek Lucy IH , Hauptmann Michael , Castelijn Daan AR , Bouma Gerd , Mulder Chris JJ , van Leeuwen Flora E , de Jong Daphne 
Published: September 2018

BackgroundThe association between celiac disease (CD) and the development of lymphoid and gastrointestinal (GI) malignancies have been reported. However, data are scarce yet needed to develop evidence‐based follow‐up programs.ObjectiveThe objective of this article is to assess relative (RR) and absolute risks of lymphoma and GI carcinoma for newly diagnosed patients.MethodsA case‐control design to determine RR was performed with cases (lymphoma or GI carcinoma) and controls (melanoma or basal cell carcinoma) diagnosed 1994–2014, retrieved from the Dutch nationwide population‐based pathology database (PALGA). Within this population, individuals with histologically proven CD before or simultaneously diagnosed with the malignancy were identified.ResultsA total of 349/301,425 cases (0.1%) and 282/576,971 (0.05%) controls were diagnosed with CD. Risk of T‐cell lymphoma, predominantly enteropathy‐associated T‐cell lymphoma (EATL), was strongly associated with CD diagnosis (RR = 35.8 (95% CI 27.1–47.4)). Although most often synchronously diagnosed, T‐cell lymphoma RR ≥ 1 year after CD diagnosis was still elevated (RR = 12.7 (95% CI 7.6–21.3)). Other CD‐associated malignancies were small bowel adenocarcinoma (RR = 11.9 (95% CI 8.2–17.2)) and esophageal squamous cell carcinoma (RR = 3.5 (95% CI 2.1–5.8)). Absolute risks were relatively low. Other types of lymphomas and GI carcinomas were not associated with CD.ConclusionIncreased risk for specific malignancies in CD should alert physicians for EATL (both intestinal and extraintestinal) and small bowel adenocarcinoma in patients with CD diagnosed at age ≥ 50 years.
Outcomes of Limited Open Achilles Repair Using Modified Ring Forceps
Authors: Telleria Jessica J.M. , Smith Jeremy T. , Ready Lauren V. , Bluman Eric M. 
Published: September 2018

Background: The optimal treatment of acute Achilles tendon ruptures remains controversial. When surgical repair is undertaken, the reported rate of infections and wound-healing complications ranges from 2% to 5%. Meta-analyses have demonstrated that minimally invasive approaches have equivalent rerupture rates, a significantly lower risk of superficial infections, and higher patient satisfaction rates compared with traditional open Achilles repair techniques. Purpose: To review the clinical outcomes of acute, limited open Achilles tendon repair using modified ring forceps and to analyze functional results using foot and ankle–specific outcome measures. Study Design: Case series; Level of evidence, 4. Methods: The clinical records of 32 consecutive patients (mean age, 44 years) with 33 acute Achilles tendon ruptures were retrospectively reviewed. All patients underwent limited open repair with modified ring forceps through a 2- to 3-cm midline incision. Suture placement into the tendon stumps was guided using a pair of ring forceps bent 30°. Three No. 2 nonabsorbable sutures were placed in the proximal and distal segments, the tendon ends were reapproximated, and the sutures were tied to secure the tendon. Outcomes from a 10-cm visual analog scale (VAS), the Foot and Ankle Ability Measure (FAAM), and the Victorian Institute of Sport Assessment–Achilles (VISA-A) were assessed. Results: At final follow-up (mean, 42.1 months [range, 6-90 months]), 31 of 32 patients (33 Achilles tendons) reported no pain in their Achilles, with a mean Achilles VAS score of 0.7 ± 4.2 of 100. The mean postoperative VISA-A score was 82.3 ± 19.5 of 100. The mean FAAM activities of daily living and sports subscores were 96.5% ± 5.2% and 85.1% ± 21.2%, respectively. Regarding current functional level, 19 of 33 tendons (57.6%) were rated as “normal,” 10 (30.3%) as “nearly normal,” and 4 (12.1%) as “abnormal”; none were rated as “severely abnormal.” There was 1 case (3.0%) of a superficial infection; there were no cases of deep infections, sural neuritis, or reruptures. The cost of the modified ring forceps technique is 5.3 to 12.1 times less than commercially available devices. Conclusion: Limited open Achilles repair with modified ring forceps provides an economical repair with excellent pain relief, favorable functional outcomes, and a very low complication rate at midterm follow-up.
Using patient factors to predict obstetric complaints and litigation: A mixed methods approach to quality improvement
Authors: Nowotny Benjamin M , Loh Erwin , Davies-Tuck Miranda , Hodges Ryan , Wallace Euan M 
Published: September 2018

Background Traditionally, managing patient complaints and medicolegal claims has been largely a reactive process. However, attention has recently turned to systematically learning from complaints and litigation to prevent recurrence. Within a high-volume maternity service, we explored whether developing predictive tools for patient complaints and litigation to support proactive management was feasible. Objectives To develop and assess two screening tools to predict the likelihood of (i) patient complaints and/or (ii) medicolegal claims arising from maternity care and to assess practitioner awareness of patient risk factors. Methods Births between 1 April 2011 and 30 April 2016 at a university hospital maternity service in Melbourne, Australia were considered. Univariate binary logistic regression was performed to identify the variables contributing to complaints and claims. Backwards-stepwise logistic regression was applied to develop each screening tool. Clinicians completed a survey to assess awareness of identified risk factors. Results In the study period, there were 41,443 births, 173 complaints and 19 claims. The complaints tool had only fair predictive capacity (receiver operating characteristic 0.72, p < 0.001) and the claims tool failed. Neither approach afforded sufficient discrimination to be useful in routine predictive modelling. One hundred and one practitioners completed the survey (response rate 15.7%). Practitioners were better at recognising risk factors for legal claims than for patient complaints. Conclusion Whilst new risk factors for patient complaints and medicolegal claims were identified, we were unable to develop a screening tool that was sufficiently discriminatory to be useful in routine predictive triaging. However, increasing practitioner awareness of key risk factors may afford opportunities to improve care quality.
Improving CLL Vγ9Vδ2-T–cell fitness for cellular therapy by ex vivo activation and ibrutinib
Authors: de Weerdt Iris , Hofland Tom , Lameris Roeland , Endstra Sanne , Jongejan Aldo , Moerland Perry D. , de Bruin Renee C. G. , Remmerswaal Ester B. M. , ten Berge Ineke J. M. , Liu Nora , van der Stelt Mario , Faber Laura M. , Levin Mark-David , Eldering Eric , Tonino Sanne H. , de Gruijl Tanja D. , van der Vliet Hans J. , Kater Arnon P. 
Published: September 2018

AbstractThe efficacy of autologous (αβ) T-cell–based treatment strategies in chronic lymphocytic leukemia (CLL) has been modest. The Vγ9Vδ2-T cell subset consists of cytotoxic T lymphocytes with potent antilymphoma activity via a major histocompatibility complex–independent mechanism. We studied whether Vγ9Vδ2-T cells can be exploited as autologous effector lymphocytes in CLL. Healthy control Vγ9Vδ2-T cells were activated by and had potent cytolytic activity against CLL cells. However, CLL-derived Vγ9Vδ2-T cells proved dysfunctional with respect to effector cytokine production and degranulation, despite an increased frequency of the effector-type subset. Consequently, cytotoxicity against malignant B cells was hampered. A comparable dysfunctional phenotype was observed in healthy Vγ9Vδ2-T cells after coculture with CLL cells, indicating a leukemia-induced mechanism. Gene-expression profiling implicated alterations in synapse formation as a conceivable contributor to compromised Vγ9Vδ2-T–cell function in CLL patients. Dysfunction of Vγ9Vδ2-T cells was fully reversible upon activation with autologous monocyte-derived dendritic cells (moDCs). moDC activation resulted in efficient expansion and predominantly yielded Vγ9Vδ2-T cells with a memory phenotype. Furthermore, ibrutinib treatment promoted an antitumor T helper 1 (TH1) phenotype in Vγ9Vδ2-T cells, and we demonstrated binding of ibrutinib to IL-2-inducible kinase (ITK) in Vγ9Vδ2-T cells. Taken together, CLL-mediated dysfunction of autologous Vγ9Vδ2-T cells is fully reversible, resulting in potent cytotoxicity toward CLL cells. Our data support the potential use of Vγ9Vδ2-T cells as effector T cells in CLL immunotherapy and favor further exploration of combining Vγ9Vδ2-T-cell–based therapy with ibrutinib.
B cells with aberrant activation of Notch1 signaling promote Treg and Th2 cell–dominant T-cell responses via IL-33
Authors: Arima Hiroshi , Nishikori Momoko , Otsuka Yasuyuki , Kishimoto Wataru , Izumi Kiyotaka , Yasuda Koubun , Yoshimoto Tomohiro , Takaori-Kondo Akifumi 
Published: September 2018

Abstract
The Notch-signaling pathway in a variety of mature B-cell neoplasms is often activated by gene alterations, but its role remains unclear. Here, we show that B cells harboring dysregulated activation of Notch1 signaling have an immunomodulatory effect on T cells by amplifying regulatory T (Treg) and T helper 2 (Th2) cell responses in an interleukin-33 (IL-33)-dependent manner. A conditional mouse model, in which constitutive expression of an active form of Notch1 is induced in B cells by Aicda gene promoter-driven Cre recombinase, revealed no obvious phenotypic changes in B cells; however, mice demonstrated an expansion of Treg and Th2 cell subsets and a decrease in cytokine production by Th1 and CD8+ T cells. The mice were susceptible to soft tissue sarcoma and defective production of CD8+ T cells specific for inoculated tumor cells, suggesting impaired antitumor T-cell activity. Gene-expression microarray revealed that altered T-cell responses were due to increased IL-33 production by Notch1-activated B cells. Knockout of IL33 or blockade of IL-33 by a receptor-blocking antibody abrogated the Treg and Th2 cell–dominant T-cell response triggered by B cells. Gene-expression data derived from human diffuse large B-cell lymphoma (DLBCL) samples showed that an activated Notch-signaling signature correlates positively with IL33 expression and Treg cell–rich gene-expression signatures. These findings indicate that B cells harboring dysregulated Notch signaling alter T-cell responses via IL-33, and suggest that aberrant activation of Notch signaling plays a role in fostering immune privilege in mature B-cell neoplasms.
Sympathetic tales: subdivisons of the autonomic nervous system and the impact of developmental studies
Authors: Ernsberger Uwe , Rohrer Hermann 
Published: September 2018

AbstractRemarkable progress in a range of biomedical disciplines has promoted the understanding of the cellular components of the autonomic nervous system and their differentiation during development to a critical level. Characterization of the gene expression fingerprints of individual neurons and identification of the key regulators of autonomic neuron differentiation enables us to comprehend the development of different sets of autonomic neurons. Their individual functional properties emerge as a consequence of differential gene expression initiated by the action of specific developmental regulators. In this review, we delineate the anatomical and physiological observations that led to the subdivision into sympathetic and parasympathetic domains and analyze how the recent molecular insights melt into and challenge the classical description of the autonomic nervous system.
Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Relapsed or Refractory Pediatric B-Cell Acute Lymphoblastic Leukemia
Authors: Lin John K. , Lerman Benjamin J. , Barnes James I. , Boursiquot Brian C. , Tan Yuan Jin , Robinson Alex Q.L. , Davis Kara L. , Owens Douglas K. , Goldhaber-Fiebert Jeremy D. 
Published: September 2018

Purpose The anti-CD19 chimeric antigen receptor T-cell therapy tisagenlecleucel was recently approved to treat relapsed or refractory pediatric acute lymphoblastic leukemia. With a one-time infusion cost of $475,000, tisagenlecleucel is currently the most expensive oncologic therapy. We aimed to determine whether tisagenlecleucel is cost effective compared with currently available treatments. Methods Markov modeling was used to evaluate tisagenlecleucel in pediatric relapsed or refractory acute lymphoblastic leukemia from a US health payer perspective over a lifetime horizon. The model was informed by recent multicenter, single-arm clinical trials. Tisagenlecleucel (under a range of plausible long-term effectiveness) was compared with blinatumomab, clofarabine combination therapy (clofarabine, etoposide, and cyclophosphamide), and clofarabine monotherapy. Scenario and probabilistic sensitivity analyses were used to explore uncertainty. Main outcomes were life-years, discounted lifetime costs, discounted quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (3% discount rate). Results With an assumption of a 40% 5-year relapse-free survival rate, tisagenlecleucel increased life expectancies by 12.1 years and cost $61,000/QALY gained. However, at a 20% 5-year relapse-free survival rate, life-expectancies were more modest (3.8 years) and expensive ($151,000/QALY gained). At a 0% 5-year relapse-free survival rate and with use as a bridge to transplant, tisagenlecleucel increased life expectancies by 5.7 years and cost $184,000/QALY gained. Reduction of the price of tisagenlecleucel to $200,000 or $350,000 would allow it to meet a $100,000/QALY or $150,000/QALY willingness-to-pay threshold in all scenarios. Conclusion The long-term effectiveness of tisagenlecleucel is a critical but uncertain determinant of its cost effectiveness. At its current price, tisagenlecleucel represents reasonable value if it can keep a substantial fraction of patients in remission without transplantation; however, if all patients ultimately require a transplantation to remain in remission, it will not be cost effective at generally accepted thresholds. Price reductions would favorably influence cost effectiveness even if long-term clinical outcomes are modest.