A hybrid Constraint Programming/Mixed Integer Programming framework for the preventive signaling maintenance crew scheduling problem

This research has been carried out as part of the PhD research project funded by Technical University of Denmark and Banedanmark company which is responsible for the operation and maintenance of the Danish railway network. This work has been partially funded by the DAASE project, EPSRC programme grant EP/J017515/1

Ownership-dependent mating tactics of minor males of the beetle Librodor japonicus (Nitidulidae) with intra-sexual dimorphism of mandibles

Intra-sexual dimorphism is found in the weapons of many male beetles. Different behavioral tactics to access females between major and minor males, which adopt fighting and alternative tactics, respectively, are thought to maintain the male dimorphism. In these species major males have enlarged weapons that they use in fights with rival males. Minor males also have small weapons in some of these species, and it is unclear why these males possess weapons. We examined the hypothesis that minor males might adopt a fighting tactic when their status was relatively high in comparison with that of other males (e.g., ownership of a territory). We observed the behavioral tactics of major and minor males of the beetle Librodor japonicus, whose males have a dimorphism of their mandibles. Major males fought for resources, whereas minor males adopted two status-dependent tactics, fighting and sneaking, to access females, depending on their ownership of a sap site. We suggest that ownership status-dependent mating tactics in minor males may maintain the intra-sexual dimorphism in this beetle.</p

Treatment of secondary hyperparathyroidism in haemodialysis patients: a randomised clinical trial comparing paricalcitol and alfacalcidol

<p>Abstract</p> <p>Background</p> <p>Secondary hyperparathyroidism is a common feature in patients with chronic kidney disease. Its serious clinical consequences include renal osteodystrophy, calcific uremic arteriolopathy, and vascular calcifications that increase morbidity and mortality.</p> <p>Reduced synthesis of active vitamin D contributes to secondary hyperparathyroidism. Therefore, this condition is managed with activated vitamin D. However, hypercalcemia and hyperphosphatemia limit the use of activated vitamin D.</p> <p>In Denmark alfacalcidol is the primary choice of vitamin D analog.</p> <p>A new vitamin D analog, paricalcitol, may be less prone to induce hypercalcemia and hyperphosphatemia.</p> <p>However, a randomised controlled clinical study comparing alfacalcidol and paricalcitol has never been performed.</p> <p>The primary objective of this study is to compare alfacalcidol and paricalcitol. We evaluate the suppression of the secondary hyperparathyroidism and the tendency towards hyperphosphatemia and hypercalcemia.</p> <p>Methods/Design</p> <p>This is an investigator-initiated cross-over study. Nine Danish haemodialysis units will recruit 117 patients with end stage renal failure on maintenance haemodialysis therapy.</p> <p>Patients are randomised into two treatment arms. After a wash out period of 6 weeks they receive increasing doses of alfacalcidol or paricalcitol for a period of 16 weeks and after a further wash out period of 6 weeks they receive the contrary treatment (paricalcitol or alfacalcidol) for 16 weeks.</p> <p>Discussion</p> <p>Hyperparathyroidism, hypercalcemia and hyperphosphatemia are associated with increased cardiovascular mortality in patients with chronic kidney disease.</p> <p>If there is any difference in the ability of these two vitamin D analogs to decrease the secondary hyperparathyroidism without causing hypercalcemia and hyperphosphatemia, there may also be a difference in the risk of cardiovascular mortality depending on which vitamin D analog that are used. This has potential major importance for this group of patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT004695</p

Milk: the new sports drink? A Review

There has been growing interest in the potential use of bovine milk as an exercise beverage, especially during recovery from resistance training and endurance sports. Based on the limited research, milk appears to be an effective post-resistance exercise beverage that results in favourable acute alterations in protein metabolism. Milk consumption acutely increases muscle protein synthesis, leading to an improved net muscle protein balance. Furthermore, when post-exercise milk consumption is combined with resistance training (12 weeks minimum), greater increases in muscle hypertrophy and lean mass have been observed. Although research with milk is limited, there is some evidence to suggest that milk may be an effective post-exercise beverage for endurance activities. Low-fat milk has been shown to be as effective, if not more effective, than commercially available sports drinks as a rehydration beverage. Milk represents a more nutrient dense beverage choice for individuals who partake in strength and endurance activities, compared to traditional sports drinks. Bovine low-fat fluid milk is a safe and effective post exercise beverage for most individuals, except for those who are lactose intolerant. Further research is warranted to better delineate the possible applications and efficacy of bovine milk in the field of sports nutrition

Psychological morbidity of celiac disease: a review of the literature

BACKGROUND: Celiac disease has been linked to decreased quality of life and certain mood disorders. The effect of the gluten free diet on these psychological aspects of the disease is still unclear. OBJECTIVES: The objective of this article is to review the literature on psychological morbidity of celiac disease. METHODS: We performed a PubMed search for the time period from 1900 until June 1, 2014, to identify papers on psychological aspects of celiac disease looking specifically at quality of life, anxiety, depression and fatigue. RESULTS: Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While aspects of these conditions may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity. Psychological symptoms may affect the quality of life and the dietary adherence. CONCLUSION: Health care professionals need to be aware of the ongoing psychological burden of celiac disease in order to support patients with this disease

Single-Batch Production of Recombinant Human Polyclonal Antibodies

We have previously described the development and implementation of a strategy for production of recombinant polyclonal antibodies (rpAb) in single batches employing CHO cells generated by site-specific integration, the SympressTM I technology. The SympressTM I technology is implemented at industrial scale, supporting a phase II clinical development program. Production of recombinant proteins by site-specific integration, which is based on incorporation of a single copy of the gene of interest, makes the SympressTM I technology best suited to support niche indications. To improve titers while maintaining a cost-efficient, highly reproducible single-batch manufacturing mode, we have evaluated a number of different approaches. The most successful results were obtained using random integration in a new producer cell termed ECHO, a CHO DG44 cell derivative engineered for improved productivity at Symphogen. This new expression process is termed the SympressTM II technology. Here we describe proof-of-principle data demonstrating the feasibility of the SympressTM II technology for single-batch rpAb manufacturing using two model systems each composed of six target-specific antibodies. The compositional stability and the batch-to-batch reproducibility of rpAb produced by the ECHO cells were at least as good as observed previously using site-specific integration technology. Furthermore, the new process had a significant titer increase

Ancient micrometeorites suggestive of an oxygen-rich Archaean upper atmosphere

It is widely accepted that Earth’s early atmosphere contained less than 0.001 per cent of the present-day atmospheric oxygen (O2) level, until the Great Oxidation Event resulted in a major rise in O2 concentration about 2.4 billion years ago1. There are multiple lines of evidence for low O2 concentrations on early Earth, but all previous observations relate to the composition of the lower atmosphere2 in the Archaean era; to date no method has been developed to sample the Archaean upper atmosphere. We have extracted fossil micrometeorites from limestone sedimentary rock that had accumulated slowly 2.7 billion years ago before being preserved in Australia’s Pilbara region. We propose that these micrometeorites formed when sand-sized particles entered Earth’s atmosphere and melted at altitudes of about 75 to 90 kilometres (given an atmospheric density similar to that of today3). Here we show that the FeNi metal in the resulting cosmic spherules was oxidized while molten, and quench-crystallized to form spheres of interlocking dendritic crystals primarily of magnetite (Fe3O4), with wüstite (FeO)+metal preserved in a few particles. Our model of atmospheric micrometeorite oxidation suggests that Archaean upper-atmosphere oxygen concentrations may have been close to those of the present-day Earth, and that the ratio of oxygen to carbon monoxide was sufficiently high to prevent noticeable inhibition of oxidation by carbon monoxide. The anomalous sulfur isotope (Δ33S) signature of pyrite (FeS2) in seafloor sediments from this period, which requires an anoxic surface environment4, implies that there may have been minimal mixing between the upper and lower atmosphere during the Archaean

The development and application of a new tool to assess the adequacy of the content and timing of antenatal care

Abstract Background: Current measures of antenatal care use are limited to initiation of care and number of visits. This study aimed to describe the development and application of a tool to assess the adequacy of the content and timing of antenatal care. Methods: The Content and Timing of care in Pregnancy (CTP) tool was developed based on clinical relevance for ongoing antenatal care and recommendations in national and international guidelines. The tool reflects minimal care recommended in every pregnancy, regardless of parity or risk status. CTP measures timing of initiation of care, content of care (number of blood pressure readings, blood tests and ultrasound scans) and whether the interventions were received at an appropriate time. Antenatal care trajectories for 333 pregnant women were then described using a standard tool (the APNCU index), that measures the quantity of care only, and the new CTP tool. Both tools categorise care into 4 categories, from ‘Inadequate’ (both tools) to ‘Adequate plus’ (APNCU) or ‘Appropriate’ (CTP). Participants recorded the timing and content of their antenatal care prospectively using diaries. Analysis included an examination of similarities and differences in categorisation of care episodes between the tools. Results: According to the CTP tool, the care trajectory of 10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as sufficient and 45,3% as appropriate. The assessment of quality of care differed significantly between the two tools. Seventeen care trajectories classified as ‘Adequate’ or ‘Adequate plus’ by the APNCU were deemed ‘Inadequate’ by the CTP. This suggests that, despite a high number of visits, these women did not receive the minimal recommended content and timing of care. Conclusions: The CTP tool provides a more detailed assessment of the adequacy of antenatal care than the current standard index. However, guidelines for the content of antenatal care vary, and the tool does not at the moment grade over-use of interventions as ‘Inappropriate’. Further work needs to be done to refine the content items prior to larger scale testing of the impact of the new measure

Hidden conformal symmetry of extreme and non-extreme Einstein-Maxwell-Dilaton-Axion black holes

The hidden conformal symmetry of extreme and non-extreme Einstein-Maxwell-Dilaton-Axion (EMDA) black holes is addressed in this paper. For the non-extreme one, employing the wave equation of massless scalars, the conformal symmetry with left temperature $T_{L}=\frac{M}{2\pi a}$ and right temperature $T_{R}=\frac{\sqrt{M^{2}-a^{2}}}{2\pi a}$ in the near region is found. The conformal symmetry is spontaneously broken due to the periodicity of the azimuthal angle. The microscopic entropy is derived by the Cardy formula and is fully in consistence with the Bekenstein-Hawking area-entropy law. The absorption cross section in the near region is calculated and exactly equals that in a 2D CFT. For the extreme case, by redefining the conformal coordinates, the duality between the solution space and CFT is studied. The microscopic entropy is found to exactly agree with the area-entropy law.Comment: V3, typos corrected, version to appear in JHE

Early intervention for adolescents with Patellofemoral Pain Syndrome - a pragmatic cluster randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Self-reported knee pain is highly prevalent among adolescents. As much as 50% of the non-specific knee pain may be attributed to Patellofemoral Pain Syndrome (PFPS). In the short term, exercise therapy appears to have a better effect than patient education consisting of written information and general advice on exercise or compared with placebo treatment. But the long-term effect of exercise therapy compared with patient education is conflicting. The purpose of this study is to examine the short- and long-term effectiveness of patient education compared with patient education and multimodal physiotherapy applied at a very early stage of the condition among adolescents.</p> <p>Methods/Design</p> <p>This study is a single blind pragmatic cluster randomised controlled trial. Four upper secondary schools have been invited to participate in the study (approximately 2500 students, aged 15-19 years). Students are asked to answer an online questionnaire regarding musculoskeletal pain. The students who report knee pain are contacted by telephone and offered a clinical examination by a rheumatologist. Subjects who fit the inclusion criteria and are diagnosed with PFPS are invited to participate in the study. A minimum of 102 students with PFPS are then cluster-randomised into two intervention groups based on which school they attend. Both intervention groups receive written information and education. In addition to patient education, one group receives multimodal physiotherapy consisting primarily of neuromuscular training of the muscles around the foot, knee and hip and home exercises.</p> <p>The students with PFPS fill out self-reported questionnaires at baseline, 3, 6, 12 and 24 months after inclusion in the study. The primary outcome measure is perception of recovery measured on a 7-point Likert scale ranging from "completely recovered" to "worse than ever" at 12 months.</p> <p>Discussion</p> <p>This study is designed to investigate the effectiveness of patient education compared with patient education combined with multimodal physiotherapy. If patient education and multimodal physiotherapy applied at an early stage of Patellofemoral Pain Syndrome proves effective, it may serve as a basis for optimising the clinical pathway for those suffering from the condition, where specific emphasis can be placed on early diagnosis and early treatment.</p> <p>Trial Registration</p> <p>clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01438762">NCT01438762</a></p