A tunable clamshell cavity for wavelike dark matter searches.

Here, we present a frequency tuning mechanism for microwave cavities designed for axion dark matter searches and show that it provides a range of at least 200 MHz for the fundamental mode TM010 resonant at ∼10 GHz. The apparatus is based on a clamshell cavity, with the two semi-cells held together at a fixed joint while the other side opens to tune the frequency of the resonant modes. Measurements of the cavity frequencies and quality factor were taken at liquid helium temperature as the aperture was increased incrementally to ∼2°. We show that the frequency shift is approximately linear with respect to the angle of aperture with no mode crossings present for an aperture less than 2°. Furthermore, the form factor and quality factor of the TM010 mode remain relatively constant throughout the tuning as predicted by simulation.

Prucalopride in intestinal pseudo obstruction, paediatric experience and systematic review.

BACKGROUND: Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity burden and have no standard management strategy. Prucalopride a highly selective serotonin receptor agonist is an effective laxative with reported extra colon action. We aim to report our experience in children with acute and chronic intestinal pseudo obstruction who responded to prucalopride and systemically review the use of prucalopride in intestinal pseudo obstruction. METHODS: A report of clinical experience and systemic review of the relevant medical databases to identify the outcome of usage of prucalopride in patients with acute and chronic intestinal pseudo obstruction. Studies meeting the selection criteria were reviewed including abstract only and case reports. RESULTS: All reported cases showed clinical response to prucalopride. There were three full text, two abstracts only and three case reports all reporting clinical improvement with prucalopride. CONCLUSION: Prucalopride appears to show promising results in children and adults with acute and chronic intestinal pseudo obstruction.

High quality factor photonic cavity for dark matter axion searches.

Searches for dark matter axions involve the use of microwave resonant cavities operating in a strong magnetic field. Detector sensitivity is directly related to the cavity quality factor, which is limited, until recently, to the use of non-superconducting metals by the presence of the external magnetic field. In this paper, we present a cavity of novel design whose quality factor is not affected by a magnetic field. It is based on a photonic structure by the use of sapphire rods. The quality factor at cryogenic temperature is in excess of 5 × 105 for a selected mode.

Cutaneous tuberculosis mimicking a mycetoma.

Atypical presentations of cutaneous tuberculosis (TB) are not uncommon and are frequently overlooked in clinical practice, leading to late diagnosis and increased morbidity. Strong clinical suspicion, histopathology, and response to antituberculous treatment are required for its diagnosis. In today's era, when TB threatens to burst into pandemics again, early diagnosis and treatment are very important for the control of disease. We are reporting a case of cutaneous TB which was initially thought to be a mycetoma.

Treatment of HCV infection in liver transplant recipients with ledipasvir and sofosbuvir without ribavirin.

BACKGROUND: Ledipasvir and sofosbuvir is a well-tolerated regimen with high sustained virological response (SVR) rates in pre-liver transplant patients infected with chronic hepatitis C virus (HCV), but data in liver transplant recipients outside of clinical trials is limited. AIM: To address this knowledge gap and assess SVR rates without the use of ribavirin in liver transplant recipients METHODS: This is a retrospective study examining the treatment of 75 post-liver transplant recipients with ledipasvir and sofosbuvir without ribavirin. Differences between SVR cohorts and predictors of SVR were analysed in an intention-to-treat (ITT) fashion. RESULTS: A total of 408 genotype 1, HCV patients were treated with ledipasvir/sofosbuvir from October 2014 to August 2015 at our centre. Seventy-three patients were post-liver transplant and were treated with a median of 2.9 years from transplant. Ledipasvir/sofosbuvir achieved an SVR12 of 95.9%. African Americans made up 28.8% of the cohort. Sixty-three per cent of patients were treated previously, including 13.7% of patients previously treated with direct-acting antivirals. Only 2.7% had recurrent allograft cirrhosis, and the majority (90.4%) was on calcineurin inhibitor based immunosuppressive therapy. Approximately 82% of patients had chronic kidney disease (CKD) stage 2 or 3. In univariate logistic regression, only detectable week 8 viral load was predictive of failure to achieve SVR. CONCLUSION: Our data confirm excellent SVR outcomes and favourable safety and tolerability profiles with ledipasvir/sofosbuvir without ribavirin in post-liver transplant recipients infected with HCV, despite treatment guidelines to use ribavirin.

Lupus vulgaris: unusual presentation on face.

Lupus vulgaris is a variant of cutaneous tuberculosis. As the disease has potential to mutilate when left untreated, leaving deforming scars and disfigurement, an early diagnosis is of paramount importance. Though the common type is plaque type, rarely mutilating and vegetative forms also are found. A 28 year old female, labourer presented with progressive annular plaque over right side of cheek extending upto right lower lid and ala of nose. There were two satellite plaques near the right side of giant lesion. On diascopy apple jelly nodule was seen. There was no regional lymhadenopathy. Histopathological examination showed many granulomas in upper dermis extending to deep dermis comprising of epitheloid cells with langhans' type of giant cells, lymphocytic infiltration & focal necrosis suggestive of lupus vulgaris. The consequences of failing to make an early diagnosis can be disastrous for the patients, as the progression of the disease can lead to necrosis, destruction of bones and cartilage leading to permanent deformity. Thus it is vital for clinicians to have a high index of suspicion of such atypical forms and take biopsy samples for histological and bacteriological studies.

Systematic review of radioguided surgery for non-palpable breast cancer.

BACKGROUND: This systematic review examines whether radioguided localization surgery (RGL) (radioguided occult lesion localization - ROLL and radioguided seed localization - RSL) for non-palpable breast cancer lesions produces lower positive margin rates than standard wire-guided localization surgery. METHODS: We performed a comprehensive literature review to identify clinical studies using either ROLL or RSL. Included studies examined invasive or in situ BC and reported pathologically assessed margin status or specimen volume/weight. Two reviewers independently assessed study eligibility and quality and abstracted relevant data on patient and surgical outcomes. Quantitative data analyses were performed. RESULTS: Fifty-two clinical studies on ROLL (n = 46) and RSL (n = 6) were identified. Twenty-seven met our inclusion criteria: 12 studies compared RGL to WGL and 15 studies were single cohorts using RGL. Ten studies were included in the quantitative analyses. Data for margin status and re-operation rates from 4 randomized controlled trials (RCT; n = 238) and 6 cohort studies were combined giving a combined odds ratio (OR) of 0.367 and 95% confidence interval (CI): 0.277 to 0.487 (p < 0.001) for margins status and OR 0.347, 95% CI: 0.250 to 0.481 (p < 0.001) for re-operation rates. CONCLUSIONS: The results of this systematic review of RGL versus WGL demonstrate that RGL technique produces lower positive margins rates and fewer re-operations. While this review is limited by the small size and quality of RCTs, the odds ratios suggest that RGL may be a superior technique to guide surgical resection of non-palpable breast cancers. These results should be confirmed by larger, multi-centered RCTs.

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-alpha monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10-50+ weeks). There was no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-alpha and CCL2 being correlated with infliximab response.

An issue of access: delivering equitable health care for newly arrived refugee children in Australia.

Newly arrived refugees and asylum seekers are faced with many difficulties in accessing effective health care when settling in Australia. Cultural, language and financial constraints, lack of awareness of available services, and lack of health provider understanding of the complex health concerns of refugees can all contribute to limiting access to health care. Understanding the complexities of a new health care system under these circumstances and finding a regular health provider may be difficult. In some cases there may be a fundamental distrust of government services. The different levels of health entitlements by visa category and (for some) detention on arrival in Australia may further complicate the provision and use of health services for providers and patients. Children are particularly at risk of suboptimal health care due to the impact of these factors combined with the effect of resettlement stresses on parents' ability to care for their children. Unaccompanied and separated children, and those in detention experience additional challenges in accessing care. This article aims to increase awareness among health professionals caring for refugee children of the challenges faced by this group in accessing and receiving effective health care in Australia. Particular consideration is given to the issues of equity, rights of asylum seekers, communication and cultural sensitivities in health care provision, and addressing barriers to health care. The aim of the paper is to alert practitioners to the complex issues surrounding the delivery of health care to refugee children and provide realistic recommendations to guide practice.

Infantile tremor syndrome and zinc deficiency.

Infantile tremor syndrome is characterized by coarse tremors, mental and physical retardation, light colored brown hair, skin pigmentation and anemia. Amongst the theories proposed for the etilogy of the disorder, the nutritional theory is most accepted. In this case report, we have presented a fourteen-month-old male child with ITS and documented zinc deficiency. Though most of the previous workers have proposed vitamin-B12 deficiency as the etimology for ITS, our report suggests that zinc deficiency could also have a causative role.

Intraosseous schwannoma of the metacarpal.

Intraosseous schwannoma (neurilemmoma) is an extremely rare, benign neoplasm, constituting less than 0.2% of primary bone tumors. It infrequently involves the bones of the hand. We present a case of intraosseous neurilemmoma of the metacarpal.

A new model for how O6-methylguanine-DNA methyltransferase binds DNA.

Human methyltransferase (hAT) catalyzes the transfer of an alkyl group from the 6-position of guanine to an active site Cys residue. The physiological role of hAT is the repair of alkylated guanine residues in DNA. However, the repair of methylated or chloroethylated guanine bases negates the effects of certain chemotherapeutic agents. A model of how hAT binds DNA might be useful in the design of compounds that could inactivate hAT. We have used computer modeling studies to generate such a model. The model utilizes a helix-loop-wing DNA binding motif found in Mu transposase. The model incorporates a flipped out guanine base in order to bring the methylated oxygen atom close to the active site Cys residue. The model is consistent with a variety of chemical and biochemical data.

AATYK: a novel tyrosine kinase induced during growth arrest and apoptosis of myeloid cells.

Apoptosis, or programmed cell death, is a process where developmental or environmental stimuli activate a genetic program to implement a series of events that culminate in cell death. To study the nature of genes that are induced during the apoptotic death of myeloid precursor cells, we utilized the 32Dcl3 cell line, which is derived from normal mouse bone marrow, is non-tumorigenic and diploid. These cells are strictly dependent on IL-3 for growth and apoptose when deprived of IL-3. However, when these cells are transferred to medium containing G-CSF, the cell number increases 4-5-fold and after 12 days the entire population is differentiated into granulocytes followed by apoptotic death. In our search for genes that are induced during apoptosis and/or terminal differentiation of 32Dcl3 cells, we identified a novel gene termed AATYK (Apoptosis Associated Tyrosine Kinase), whose expression is dramatically upregulated during IL-3 deprivation as well as G-CSF-induced terminal differentiation. In this report, we describe the sequence of the cDNA clone, derived from the mRNA transcript of this gene. These studies show that this gene encodes a protein with a tyrosine kinase domain at the N-terminal end and a proline-rich domain at the C-terminal end. We also report that the expression of this gene is blocked in v-abl or bcr-abl transformed myeloid cells which are unable to apoptose when grown in the absence of IL-3. However, AATYK expression is induced in 32D cells transformed by the v-abl gene when these cells are incubated in the presence of DMSO, which induces growth arrest and apoptotic death of the cells. On the other hand, DMSO fails to induce apoptosis or AATYK expression in 32D cells transformed by the bcr-abl oncogene, suggesting that AATYK expression may be a necessary pre-requisite for the induction of growth arrest and/or apoptosis of myeloid precursor cells.

Primary binding domain of bovine von Willebrand factor fragment expressed in E. coli.

Bovine vWF cDNA has been cloned from a bovine endothelial cell library. A fragment of this cDNA, corresponding to amino acid sequence Leu 469-Ser 723, called primary adhesion domain (PAD-1), and containing the binding sites for platelet glycoprotein Ib (GPIb), heparin and collagen, has been expressed in E. coli. The reduced and alkylated form of fragment PAD-1 inhibited native vWF binding to GPIb. Fragment PAD-1 bound to heparin and botrocetin in a specific and dose dependent manner as did the native vWF. In a solid-phase assay, fragment PAD-1 bound to calf skin collagen in contrast to a human vWF recombinant fragment (Ser 445-Val 733) which was inactive in the same assay. The studies presented in this paper demonstrated that the A1 domain of bovine vWF contained the GPIb, heparin, botrocetin as well as collagen binding sites and that integrity of the disulfide bond (Cys 509-Cys 695), did not seem to be essential for binding of bovine vWF fragment to GPIb.

ASP514 within the A1 domain of bovine von Willebrand factor is required for interaction with platelet glycoprotein Ib.

A mutant PAD-1 (D514-->Q) of the recombinant fragment PAD-1 comprising Leu469-Ser723 of the A1 domain of bovine von Willebrand factor (vWF) neither inhibited the binding of [125I]vWF to platelets nor the agglutination of human platelets induced by bovine vWF. PAD-1, on the other hand, inhibited human platelet agglutination induced by bovine vWF and [125I]vWF binding to human platelets. Collagen binding properties of the mutant, however, were indistinguishable from those of PAD-1. These results suggested that Asp514 within the A1 domain of vWF is required for interaction of bovine vWF with GPIb receptor on human platelets.

Ligand binding assays with recombinant proteins refolded on an affinity matrix.

This paper describes a procedure for performing ligand binding assays with recombinant proteins or protein fragments that can bind to an affinity matrix in the presence or absence of a denaturing agent but which require the presence of the denaturing agent to remain in solution. The method involves coupling of a known amount of the protein in a denaturing medium to a known amount of the affinity matrix, replacing the denaturing agent with a physiological buffer, and finally using the suspension of this protein-coupled matrix as the source of the recombinant protein to be studied for its functional properties. A constant volume of this suspension is incubated with different concentrations of a radiolabeled ligand. Radioactivity bound to the protein-coupled affinity matrix is determined after centrifugation and washing of the pellet. Nonspecific binding is determined either by using the uncoupled affinity matrix or by the standard technique of measuring the binding in the presence of excess unlabeled ligand.