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Background/objective: Parathyroid carcinoma is a rare entity presenting as parathyroid hormone (PTH) dependent hypercalcemia. Our objective was to report a case of metastatic parathyroid carcinoma in a middle-aged woman, who presented with refractory hypercalcemia and the strategies we used to induce remission. Case report: A 47 year old lady with a past history of a left superior parathyroid adenoma excision, presented with recurrent PTH dependent hypercalcemia. An ultrasonography of the neck and parathyroid scintigraphy were normal. Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) scan picked up metabolically active lesions in the lingular segment of the left lung and another lesion in the diaphragmatic pleura of the left hemi-thorax. Following metastectomy of the lung nodules, she developed symptomatic hypocalcemia with a reduction of serum PTH levels. The histopathology and immunoprofile were consistent with metastatic carcinoma. The PTH levels started rising 2 months after the surgery, with calcium levels remaining stable on cinacalcet, denosumab and cabozantinib. Discussion: Parathyroid carcinoma is a rare endocrine malignancy with typically indolent, yet progressive course. There is no consensus on the treatment and follow-up of parathyroid carcinoma, owing to its rarity. The greatest likelihood of cure is achieved if complete resection of all malignant tissue is successful at the time of initial surgery. Surgical reduction of the tumor mass may also render the patient's hypercalcemia more amenable to medical treatment with hydration, potent intravenous bisphosphonates, denosumab and cinacalcet. Conclusion: Surgical debulking of the metastatic lesions, followed by medical management of hypercalcemia offers promising results in the management of metastatic parathyroid carcinoma.

Chronic consumption of a large quantity of alcohol often results in the disruption of the communication between the nervous, endocrine and immune systems leading to profound and serious consequences at the physiological and behavioral levels. The overall impact of excessive alcohol consumption on bone health, metabolic profile and body composition, especially at moderate levels, is not well understood. Chronic excessive alcohol consumption adversely affects bone health through multiple mechanisms leading to low bone mass. It may also be significantly associated with various components on the metabolic syndrome. This review summarizes the findings from published studies that provide consistent evidence on the various effects of alcohol abuse on the bone health and metabolism.

Familial hypercholesterolaemia (FH) is an autosomal dominant inherited disorder of lipoprotein metabolism caused by defects in the low-density lipoprotein receptor (LDLR) gene. It is characterized by high low-density lipoprotein (LDL) cholesterol levels, premature cardiovascular disease (CVD), and tendon xanthomas. We present the case of a 26-year-old gentleman who presented with multiple nodular eruptions over the extensor aspects of upper and lower limbs and was diagnosed as FH on the basis of positive family history, typical lipid profile abnormalities, and biopsy of the nodule consistent with tendon xanthomas. The diagnosis and management of this case is deftly feasible at the primary care level.

We present the case of a 45-year-old lady with long standing hypothyroidism who was euthyroid on replacement for many years, but stopped responding even to supraphysiological doses of LT4 since the last five years. She complained of abdominal discomfort, bloating, and nausea. She did not have diarrhea or weight loss. Levothyroxine absorption test was done which was suggestive of malabsorption and she was started on triple therapy for H. pylori eradication after confirmation of diagnosis. After 10 days of treatment initiation, she developed symptoms of thyrotoxicosis with her supraphysiological dose of LT4, which was then tapered to a lower dose. Euthyroid state was ultimately achieved with lower doses of LT4 replacement.

Traces the origin and development of a text-based computer-assisted language-learning activity, namely the shuffling of sentences of a text and the reconstruction on screen of that text. Emphasizes the elements of continuity between the first version, implemented on a mainframe computer, and the latest version. Classroom use of the latest version is discussed, with special attention to the methodology of reciprocal learning (Author/VWL)

Changes in the diagnosis and treatment of helminthic infection were examined during a longitudinal study in a rural community in Guatemala. Self-diagnosis was predominant, with an increase in perceived helminthic infection during an economic crisis within the community. Allium sativum L. and Chenopodium ambrosoides L. were used as anthelmintics, often in conjunction with commercial drugs. During the economic crisis the use of plants as treatment for perceived infection increased whereas use of commercial helminthic medicine decreased. Dietary modifications were observed during periods of perceived infection, but were not consistent in the food items modified or the nature of the modification. Within the community individuals exhibited considerable heterogeneity in their approaches to treatment.

We present a coupled retrospective forecast (hindcast) study using the Met Office Global Coupled Model, version 2 (GC2), in which we identify and mitigate causes of initialization shock that lead to rapid error growth in sea ice forecasts. Sea ice state variables and volume budget terms as a function of forecast lead time are evaluated relative to analyses from an uncoupled Met Office ocean–sea ice analysis system [Forecast Ocean Assimilation Model, version 13 (FOAMv13)]. Two sources of initialization shock are highlighted and addressed, both of which are related to effective differences in physics between the analysis system and coupled forecast model. The primary shock to sea ice state variables arises from the use of a salinity-independent freezing temperature for seawater in GC2 as opposed to a salinity-dependent formulation in FOAMv13. A secondary effect arises from differences in the sea ice roughness and hence air–ice drag in the GC2 forecast model compared to the FOAMv13 analysis system. Generalizing from the findings of this study, we suggest that using nonnative analyses as initial conditions for coupled numerical weather prediction (NWP) studies will likely make them prone to initialization shock in some model components, to the detriment of forecast skill. To reduce the undesirable impacts of initialization shock on short-range forecast skill noted in this study we would therefore recommend the use of initial conditions (analyses) physically consistent with the native model components of the coupled forecast model, a native coupled analysis likely being the optimal initialization method. [ABSTRACT FROM AUTHOR]

Background: TNF α is a proinflammatory cytokine associated with the inflammatory response of Crohn's disease. Treatment with TNF a antibodies is efficacious in active disease. Thalidomide has recognised TNFα inhibitory [...]

Abstract: The Global Coupled 3 (GC3) configuration of the Met Office Unified Model is presented. Among other applications, GC3 is the basis of the United Kingdom's submission to the Coupled Model Intercomparison Project 6 (CMIP6). This paper documents the model components that make up the configuration (although the scientific descriptions of these components are in companion papers) and details the coupling between them. The performance of GC3 is assessed in terms of mean biases and variability in long climate simulations using present‐day forcing. The suitability of the configuration for predictability on shorter time scales (weather and seasonal forecasting) is also briefly discussed. The performance of GC3 is compared against GC2, the previous Met Office coupled model configuration, and against an older configuration (HadGEM2‐AO) which was the submission to CMIP5. In many respects, the performance of GC3 is comparable with GC2, however, there is a notable improvement in the Southern Ocean warm sea surface temperature bias which has been reduced by 75%, and there are improvements in cloud amount and some aspects of tropical variability. Relative to HadGEM2‐AO, many aspects of the present‐day climate are improved in GC3 including tropospheric and stratospheric temperature structure, most aspects of tropical and extratropical variability and top‐of‐atmosphere and surface fluxes. A number of outstanding errors are identified including a residual asymmetric sea surface temperature bias (cool northern hemisphere, warm Southern Ocean), an overly strong global hydrological cycle and insufficient European blocking. [ABSTRACT FROM AUTHOR]

Non-tubal ectopic pregnancies are a rare subgroup of ectopic pregnancies implanted at sites other than the Fallopian tube. Mortality from non-tubal ectopic pregnancies is higher compared with that for tubal ectopic pregnancies, and they are becoming more common, partly due to the rising incidence of Caesarean sections and use of assisted reproductive technologies. Non-tubal ectopic pregnancies can be especially difficult to treat. Surgical treatment is complex, and follow-up after medical treatment is usually protracted. There is therefore a need for more effective medical therapies to resolve non-tubal ectopic pregnancies and reduce operative intervention. We have recently reported successful use of combination gefitinib (an orally available epidermal growth factor receptor inhibitor) and methotrexate for treatment of tubal pregnancies. To our knowledge, this combination has not been used to treat non-tubal pregnancies. Here we report the use of combination gefitinib and methotrexate to treat eight women with stable, non-tubal ectopic pregnancies at two tertiary academic teaching hospitals (Edinburgh, UK and Melbourne, Australia); five interstitial and three Caesarean section scar ectopic pregnancies. Pretreatment serum hCG levels ranged from 2458 to 48 550 IU/l, and six women had pretreatment hCG levels >5000 IU/l. The women were co-administered 1-2 doses of i.m. methotrexate (50 mg/m² on Day 1, ± Day 4 or Day 7) with seven once daily doses of oral gefitinib (250 mg). The women were monitored until complete resolution of the ectopic pregnancy, defined as a serum hCG <15 IU/l. Time to resolution (days from first methotrexate dose until serum hCG <15 IU/l), safety and tolerability, complication rates and subsequent fertility outcomes were also recorded. All eight women were successfully treated with combination gefitinib and methotrexate. The most common side effects were transient acne/rash and diarrhoea, known side effects of gefitinib. All women promptly resumed menstruation and importantly, three women subsequently conceived spontaneously. Two have delivered a healthy infant at term and the third is currently in her second trimester of pregnancy. Hence, our case series supports a future clinical trial to determine the efficacy of combination gefitinib and methotrexate to treat non-tubal ectopic pregnancies. [ABSTRACT FROM AUTHOR]

Communication establishment is crucial for rescue operations in disaster affected areas. A standard tool for communication is the use of cell phones. However, they can be useless in situations where the cellular network’s base stations are damaged in a disaster. A contemporary approach to re-establishing a communication network is by hosting base stations in drones. However, low battery life and difficulty in calculating the number of drones needed in different terrains are limitations of the above approach. This paper introduces a novel terrain-aware algorithm that calculates the minimum number of drones needed to cover an area with no voids in the network coverage. Our method ensures that the drones are deployed at optimal heights to maximize the average leftover energy in the network. We apply the algorithm for an actual location in Pettimudi, India and find the optimal number and positions of the drones to cover the area effectively without voids. In addition, we provide a simulation of the the communication establishment using above drones, and our experiments yield an average network efficiency of 98%, showing the effectiveness of our method.

Background. Inflammation, together with related oxidative stress, is linked with the etiology of kwashiorkor, a form of severe acute malnutrition in children. A diet rich in anti-inflammatory and antioxidant phytochemicals may offer potential for the prevention and treatment of kwashiorkor. We selected and assayed five leafy green vegetables, two wild fruits, and six medicinal plants from Kenya for their antioxidant and anti-inflammatory properties. Consensus regarding medicinal plant use was established from ethnobotanical data. Methods. Antioxidant activity and phenolic content were determined using the oxygen radical absorbance capacity (ORAC) assay and Folin-Ciocalteu procedure, respectively. Anti-inflammatory activity was assessed in vitro targeting the inflammatory mediator tumour necrosis factor-alpha (TNF-α). Results. Mangifera indica (leaves used medicinally) showed the greatest antioxidant activity (5940 ± 632 µM TE/µg) and total phenolic content (337 ± 3 mg GAE/g) but Amaranthus dubius (leafy vegetable) showed the greatest inhibition of TNF-α (IC50 = 9 ± 1 μg/mL), followed by Ocimum americanum (medicinal plant) (IC50 = 16 ± 1 μg/mL). Informant consensus was significantly correlated with anti-inflammatory effects among active medicinal plants (r2=0.7639, P=0.0228). Conclusions. Several plant species commonly consumed by Kenyan children possess activity profiles relevant to the prevention and treatment of kwashiorkor and warrant further investigation. [ABSTRACT FROM AUTHOR]

As stem cells undergo differentiation, mitochondrial DNA (mtDNA) copy number is strictly regulated in order that specialized cells can generate appropriate levels of adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) to undertake their specific functions. It is not understood whether tumor-initiating cells regulate their mtDNA in a similar manner or whether mtDNA is essential for tumorigenesis. We show that human neural stem cells (hNSCs) increased their mtDNA content during differentiation in a process that was mediated by a synergistic relationship between the nuclear and mitochondrial genomes and results in increased respiratory capacity. Differentiating multipotent glioblastoma cells failed to match the expansion in mtDNA copy number, patterns of gene expression and increased respiratory capacity observed in hNSCs. Partial depletion of glioblastoma cell mtDNA rescued mtDNA replication events and enhanced cell differentiation. However, prolonged depletion resulted in impaired mtDNA replication, reduced proliferation and induced the expression of early developmental and pro-survival markers including POU class 5 homeobox 1 (OCT4) and sonic hedgehog (SHH). The transfer of glioblastoma cells depleted to varying degrees of their mtDNA content into immunocompromised mice resulted in tumors requiring significantly longer to form compared with non-depleted cells. The number of tumors formed and the time to tumor formation was relative to the degree of mtDNA depletion. The tumors derived from mtDNA depleted glioblastoma cells recovered their mtDNA copy number as part of the tumor formation process. These outcomes demonstrate the importance of mtDNA to the initiation and maintenance of tumorigenesis in glioblastoma multiforme. [ABSTRACT FROM AUTHOR]

A common practice in personnel tour scheduling is to limit the number of permissible daily shift starting times. Accordingly, an important subproblem that arises in tour-scheduling problems is the selection of those starting times that are conducive to efficient satisfaction of labour requirements. A previously published heuristic for this problem is sequential in nature, whereby a subset of starting times is selected in the first stage and tours are constructed using the chosen starting times in the second stage. We propose an integrative procedure that overcomes many of the limitations inherent in the sequential approach. Our procedure, which uses tabu search for starting time selection and a cutting plane method for tour construction, was compared to integer programming and the previously published heuristic in two experiments using test conditions from the airport staffing literature. Although all methods performed well when the labour requirement patterns were consistent across days of the week, the new procedure yielded the best performance when such patterns were inconsistent. [ABSTRACT FROM AUTHOR]

Objective: To establish the feasibility of conducting a home-based progressive resistance exercise programme to improve calf muscle pump function in community-based patients with venous leg ulcers. Method: Participants were randomised to receive a 12-week progressive resistance exercise programme using heel raises in addition to compression. The control was usual care in addition to compression. Randomisation was stratified by ulcer duration and ulcer size. Air plethysmography was used to determine changes in calf muscle pump function from baseline. Changes in ulcer parameters were measured using the SilhouetteMobile device. Results: Forty participants were randomised. There were significantly greater improvements in ejection fraction of the calf muscle in the exercise group compared with the control (usual care) group (mean difference 18.5%, 95% CI 0.03 to 36.6%, p<0.05). Other parameters improved in the exercise group but the mean differences were not significant. Adherence with prescribed exercises was 81% and there was no significant difference in the numbers reporting adverse events. There were also no significant differences in ulcer healing parameters (change in area, percentage change in area, number healed at 12 weeks, time to healing). Conclusion: A community-based randomised trial of progressive resistance exercise is feasible. The prescribed exercises appeared to increase ejection fraction, but the effect of exercise on ulcer healing requires further investigation. Declaration of interest: The study was funded by the Health Research Council of New Zealand. ARANZ Medical provided access to a SilhouetteMobile device. [ABSTRACT FROM AUTHOR]

In fall of 2007, a survey was administered to the membership of the Associated Schools of Construction (ASC) to evaluate member perspectives on scholarly standards as they relate to the International Journal of Construction Education and Research (“Journal”). The objectives of this study were to 1) survey respondent understanding of Journal aims and scope, 2) assess respondent interpretations of scholarly work, and 3) survey respondent attitudes on the overall effectiveness of the Journal submission and peer-review process. Of 106 respondents, 74% had previously published or reviewed for the Journal. While 65% of respondents indicated that the aim of the Journal was to publish scholarly works in both construction education and research, respondents were near equally divided on whether non-original research constitutes scholarly work. Respondents agreed or strongly agreed that Journal topics (87%), title (93%), and assessment criteria (83%) were appropriate. Ninety-four percent of peer reviewers felt the Journal review process was timely and efficient, compared with 78% of authors. Only 66% of authors felt peer reviewers had the knowledge necessary to effectively review their manuscripts. More than three in four (76%) reviewers stated that they relied more on their own intuition than Journal guidelines when conducting peer reviews. Of all respondents, two-thirds (66%) consider the Journal to be a “top tier” publication. [ABSTRACT FROM AUTHOR]

TRAIL/Apo-2L has shown promise as an anti-glioma drug, based on investigations of TRAIL sensitivity in established glioma cell lines, but it is not known how accurately TRAIL signalling pathways of glioma cells in vivo are reproduced in these cell lines in vitro. To replicate as closely as possible the in vivo behaviour of malignant glioma cells, 17 early passage glioma cell lines and 5 freshly resected gliomas were exposed to TRAIL-based agents and/or chemotherapeutic drugs. Normal human hepatocytes and astrocytes and established glioma cell lines were also tested. Cross-linked TRAIL, but not soluble TRAIL, killed both normal cell types and cells from three tumours. Cells from only one glioma were killed by soluble TRAIL, although only inefficiently. High concentrations of cisplatin were lethal to glioma cells, hepatocytes and astrocytes. Isolated combinations of TRAIL and chemotherapy drugs were more toxic to particular gliomas than normal cells, but no combination was generally selective for glioma cells. This study highlights the widespread resistance of glioma cells to TRAIL-based agents, but suggests that a minority of high-grade glioma patients may benefit from particular combinations of TRAIL and chemotherapy drugs. In vitro sensitivity assays may help identify effective drug combinations for individual glioma patients. [ABSTRACT FROM AUTHOR]