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AbstractThe Academic Medical Center (AMC) in Amsterdam, The Netherlands, recently opened the ‘Children’s Muscle Center Amsterdam’ (CMCA). The CMCA diagnoses and treats children with neuromuscular diseases. The patients with such diseases require care from a variety of clinicians. Through the establishment of the CMCA, children and their parents will generally visit the hospital only once a year, while previously they used to visit on average six times a year. This is a major improvement, because the hospital visits are both physically and psychologically demanding for the patients. This paper describes how quantitative modelling supports the design and operations of the CMCA. First, an integer linear program is presented that selects which patients are to be invited for a treatment day and schedules the required combination of consultations, examinations and treatments on one day. Second, the integer linear program is used as input to a simulation study to estimate the capacity of the CMCA, expressed in terms of the distribution of the number patients that can be seen on one diagnosis day. Finally, a queueing model is formulated to predict the access time distributions based upon the simulation outcomes under various demand scenarios. Its contribution on the case under study is twofold. First, we design highly constrained appointment schedules for multiple patients that require service from multiple disciplines’ resources. Second, we study the effect of the trade-offs between scheduling constraints and access times. As such, the contribution of this case study paper is that it illustrates the value of applying Operations Research techniques in complex healthcare settings, by designing context-specific combinations of mathematical models, thereby improving delivery of the highly-constrained multidisciplinary care.

A global increase in the demand for crop-based biofuels may be met by cropland expansion, and could require the sacrifice of natural vegetation. Such land transformation alters the carbon and nitrogen cycles of the original system, and causes significant greenhouse-gas emissions, which should be considered when assessing the global warming performance of crop-based biofuels. As an indicator of this performance we propose the use of greenhouse-gas payback time (GPBT), that is, the number of years it takes before the greenhouse-gas savings due to displacing fossil fuels with biofuels equal the initial losses of carbon and nitrogen stocks from the original ecosystem. Spatially explicit global GPBTs were derived for biofuel production systems using five different feedstocks (corn, rapeseed, soybean, sugarcane and winter wheat), cultivated under no-input and high-input farm management. Overall, GPBTs were found to range between 1 and 162 years (95% range, median: 19 years) with the longest GPBTs occurring in the tropics. Replacing no-input with high-input farming typically shortened the GPBTs by 45 to 79%. Location of crop cultivation was identified as the primary factor driving variation in GPBTs. This study underscores the importance of using spatially explicit impact assessments to guide biofuel policy.

Recent studies demonstrate widespread expression of ghrelin among tissues and have uncovered its pleiotropic nature. We have examined gene expression of ghrelin and its two receptor splice variants, growth hormone secretagogue receptors (GHS-R) 1a and 1b, in human bone biopsies and in the human pre-osteoblastic SV-HFO cell line during differentiation. Additionally, we examined proliferative effects of ghrelin and unacylated ghrelin (UAG) in differentiating and non-differentiating cells. We detected GHS-R1b mRNA in human bone and osteoblasts but not ghrelin’s cognate receptor GHS-R1a, using two different real-time PCR assays and both total RNA and mRNA. In osteoblasts GHS-R1b mRNA expression remained low during the first 14 days of culture, but increased 300% in differentiating cells by day 21. Both human bone biopsies and osteoblasts expressed ghrelin mRNA, and osteoblasts were found to secrete ghrelin. Overall, ghrelin gene expression was greater in differentiating than non-differentiating osteoblasts, but was not increased during culture in either group. Ghrelin and UAG induced thymidine uptake dose-dependently, peaking at 1 and 10 nM respectively, at day 6 of culture in both non-differentiating and differentiating osteoblasts. The proliferative response to ghrelin and UAG declined with culture time and state of differentiation. The proliferative effects of ghrelin and UAG were suppressed by inhibitors of extracellular-signal-regulated kinase (ERK) and phosphoinositide-3 kinase, and both peptides rapidly induced ERK phosphorylation. Overall, our data suggest new roles for ghrelin and UAG in modulating human osteoblast proliferation via a novel signal transduction pathway.

Video-assisted endoscopic techniques have reduced operative trauma in adult thoracic and general surgery, but applications in children with congenital heart disease have been limited. We report the development of video-assisted thoracic surgery procedures for neonates and infants with cardiovascular disease. Endoscopic instruments and techniques for pediatric cardiovascular procedures were designed and tested in the animal laboratory. Forty-eight operations were subsequently performed in 46 pediatric patients ranging in age from 2 hours to 14 years (median 9 months), weighing from 575 grams to 54 kg (median 8.5 kg). Clinical applications included seven different procedures: patent ductus ateriosus interruption in infants ( n = 26) and premature neonates ( n = 5), vascular ring division ( n = 8), pericardial drainage and resection ( n = 3), arterial and venous collateral interruption ( n = 2), thoracic duct ligation ( n = 2), epicardial pacemaker lead insertion ( n = 1), and diagnostic thoracoscopy ( n = 1), and diagnostic thoracoscopy ( n = 1). there was no operative mortality. Technical success, defined as a video-assisted procedure completed without incising chest wall muscle or spreading the ribs, was achieved in 39 of 48 procedures (82%), with thoracotomy required to complete nine procedures. Most patients (22/25, 88%) undergoing elective ductus ligation were extubated in the operating room and discharged from the hospital within 48 hours of the operation. Eight of the last 10 patients having ductus ligation were discharged on the first postoperative day. Residual ductal flow was assessed by (1) transesophageal echocardiography in the operating room (incidence: 0/25, 0%, 70% CL 0% to 7.3%); (2) discharged auscultation (incidence: 1/30, 3%, 70% CL 0.5% to 10.8%); and (3) follow-up Doppler echocardiography (incidence: 1/30, 3%, 70% CL 5.4% to 22.6%). Video-assisted thoracoscopic techniques can be safely applied to pediatric patients with patent ductus arteriosus and vascular rings and may become an effective addition to the staged management of more complex forms of congenital heart disease. (J THORAC C ARDIOVASC S URG 1995; 109: 499-508)

(Abstracted from BJOG2017;124:243–249)There is a 2% lifetime risk among women of developing a cyst or abscess of the Bartholin gland. These usually occur during reproductive ages; both can limit activity, and an abscess can also cause extreme pain.