Metrology of infrared superconducting bolometers with a backshort.

We present the detailed metrology of a superconducting Transition-Edge Sensor (TES) absorber-coupled bolometer array bonded to a variable-delay backshort to form an integral field unit. The backshort is shaped as a wedge to continuously vary the electrical phase delay of the bolometer absorber reflective termination across the array. This resonant absorber termination structure is used to define a spectral response over a 4:1 bandwidth in the far-infrared, from ∼30 to 120 µm. The metrology of the backshort-bolometer array hybrid was achieved with a laser confocal microscope and a compact cryogenic system that provides a well-defined thermal (radiative and conductive) environment for the hybrid when cooled to ∼10 K. The results show the backshort free-space delays do not change with cooling. The estimated backshort slope is 1.58 milli-radians and within 0.3% of the targeted value. The sources of error in the free-space delay of the hybrid and optical cryogenic metrology implementations are discussed in detail. We also present measurements of the bolometer's single-crystal silicon membrane topography. The membranes deform and deflect out-of-plane under both warm and cold conditions. Intriguingly, the optically active area of the membranes tends to flatten when cold and repeatably achieve the same mechanical state over many thermal cycles; hence, no evidence for thermally-induced mechanical instability is observed. Most of the cold deformation is sourced from thermally-induced stress in the metallic layers comprising the TES element of the bolometer pixels. These results provide important considerations for the design of ultra-low-noise TES bolometers.

Sub-Kelvin cooling for two kilopixel bolometer arrays in the PIPER receiver.

The Primordial Inflation Polarization Explorer (PIPER) is a balloon-borne telescope mission to search for inflationary gravitational waves from the early universe. PIPER employs two 32 × 40 arrays of superconducting transition-edge sensors, which operate at 100 mK. An open bucket Dewar of liquid helium maintains the receiver and telescope optics at 1.7 K. We describe the thermal design of the receiver and sub-Kelvin cooling with a continuous adiabatic demagnetization refrigerator (CADR). The CADR operates between 70 and 130 mK and provides ≈10 µW cooling power at 100 mK, nearly five times the loading of the two detector assemblies. We describe electronics and software to robustly control the CADR, overall CADR performance in flightlike integrated receiver testing, and practical considerations for implementation in the balloon float environment.

Polarisation of equine pregnancy outcome associated with a maternal MHC class I allele: Preliminary evidence.

Identification of risk factors which are associated with severe clinical signs can assist in the management of disease outbreaks and indicate future research areas. Pregnancy loss during late gestation in the mare compromises welfare, reduces fecundity and has financial implications for horse owners. This retrospective study focussed on the identification of risk factors associated with pregnancy loss among 46 Thoroughbred mares on a single British stud farm, with some but not all losses involving equid herpesvirus-1 (EHV-1) infection. In a sub-group of 30 mares, association between pregnancy loss and the presence of five common Thoroughbred horse haplotypes of the equine Major Histocompatibility Complex (MHC) was assessed. This involved development of sequence specific, reverse transcriptase polymerase chain reactions and in several mares, measurement of cytotoxic T lymphocyte activity. Of the 46 mares, 10 suffered late gestation pregnancy loss or neonatal foal death, five of which were EHV-1 positive. Maternal factors including age, parity, number of EHV-1 specific vaccinations and the number of days between final vaccination and foaling or abortion were not significantly associated with pregnancy loss. In contrast, a statistically significant association between the presence of the MHC class I B2 allele and pregnancy loss was identified, regardless of the fetus/foal's EHV-1 status (p=0.002). In conclusion, this study demonstrated a significantly positive association between pregnancy loss in Thoroughbred mares and a specific MHC class I allele in the mother. This association requires independent validation and further investigation of the mechanism by which the mare's genetic background contributes to pregnancy outcome.

A case report on over-replacement of oral calcium supplements causing acute pancreatitis.

A 42-year-old female teetotaller presented via the accident and emergency department with a 2-day history of vomiting and upper abdominal pain. She was diagnosed with acute pancreatitis. The aetiology of the pancreatitis was identified as hypercalcaemia secondary to oral calcium supplementation. The hypercalcaemia was corrected by stopping calcium supplements and aggressive fluid resuscitation. A thorough literature search did not show any case reports in which the aetiology of pancreatitis was oral calcium supplement over-replacement.

Single-use NPWT for the treatment of complex orthopaedic surgical and trauma wounds.

Orthopaedic limb reconstruction patients often have wounds that are difficult to heal either due to the underlying problems, their surgery, underlying comorbidities or a combination of these factors. Negative pressure wound therapy (NPWT) is a useful tool with which to manage these wounds; however, many systems are not ideal for use in the patient's home, due in part to size and complexity. There are also staff training issues if transferring patients to an area which does not routinely use negative pressure systems. This paper reports the outcomes for some of the patients who were treated with a novel, single-use NPWT device in a orthopaedic trauma/limb reconstruction unit.

Monitoring agricultural rodenticide use and secondary exposure of raptors in Scotland.

Despite the documented risk of secondary poisoning to non-target species by anticoagulant rodenticides there is no statutory post-approval monitoring of their use in the UK. This paper presents results from two Scottish monitoring schemes for the period 2000-2010; recording rodenticide use on arable farms and the presence of residues in raptor carcasses. More than three quarters of arable farms used anticoagulant rodenticides; predominately the second generation compounds difenacoum and bromadiolone. There was widespread exposure to anticoagulant rodenticides in liver tissues of the raptor species tested and the residues encountered generally reflected agricultural use patterns. As found in other studies, Red Kites (Milvus milvus) appeared to be particularly vulnerable to rodenticide exposure, 70 % of those sampled (n = 114) contained residues and 10 % died as a result of rodenticide ingestion. More unexpectedly, sparrowhawks (Accipiter nisus), which prey almost exclusively on birds, had similar exposure rates to species which prey on rodents. Although, with the exception of kites, confirmed mortality from rodenticides was low, the widespread exposure recorded is concerning. Particularly when coupled with a lack of data about the sub-lethal effects of these compounds. This raises questions regarding whether statutory monitoring of use is needed; both to address whether there are deficiencies in compliance with approval conditions or whether the recommended risk management procedures are themselves adequate to protect non-target wildlife.

Intussusception secondary to a solitary peritoneal lung metastasis.

We report a 77-year-old woman, newly diagnosed with a malignant lung neoplasm of indeterminate nature who presented with profuse bilious vomiting without abdominal distension, pain or constipation. CT confirmed proximal small bowel obstruction. Laparotomy found a large area of intussusception from an intraluminal mass in the small bowel, which was resected and a primary anastomosis performed. Histology reported the mass as metastatic non-small-cell carcinoma and brought clarity to the primary tumour diagnosis. The patient made a good recovery from the operation, but unfortunately died a few months later from complications of her metastatic disease.

Factors associated with outcome and duration of therapy in outpatient parenteral antibiotic therapy (OPAT) patients with skin and soft-tissue infections.

This study was designed to identify factors associated with adverse outcomes and increased duration of parenteral therapy in patients with skin and soft-tissue infections (SSTIs) managed with outpatient parenteral antibiotic therapy (OPAT). A retrospective cohort study interrogating variables recorded prospectively in an electronic OPAT patient database was performed. 'OPAT failure' was defined as hospitalisation following initiation of OPAT, or adverse event or progression of infection necessitating a change in antibiotic therapy. Variables associated with failure or increased duration of therapy were identified via univariate and multiple logistic regression analyses. In total, 963 first patient episodes of OPAT-treated SSTIs were observed; 84% were treated with daily ceftriaxone and 15% with teicoplanin (three daily loading doses then three times per week). Progression of infection was observed in 2.8% of cases, inpatient management was required in 6% and significant adverse events occurred in 7.1%. Overall OPAT success was 87.1%. Female sex, diabetes and treatment with teicoplanin were independently associated with OPAT failure. A significant reduction in duration of OPAT therapy was observed over time. A longer duration of intravenous therapy was associated with meticillin-resistant Staphylococcus aureus (MRSA), older age, vascular disease, a diagnosis of bursitis, and treatment with teicoplanin. Non-inpatient referrals, management via a nurse-led patient group direction, and treatment with ceftriaxone were associated with reduced duration of OPAT. For selected patients with SSTIs, OPAT was generally safe and effective, but specific patient groups were identified with more complex management pathways and poorer outcomes.

Does small mammal prey guild affect the exposure of predators to anticoagulant rodenticides?

Ireland has a restricted small mammal prey guild but still includes species most likely to consume anticoagulant rodenticide (AR) baits. This may enhance secondary exposure of predators to ARs. We compared liver AR residues in foxes (Vulpes vulpes) in Northern Ireland (NI) with those in foxes from Great Britain which has a more diverse prey guild but similar agricultural use of ARs. Liver ARs were detected in 84% of NI foxes, more than in a comparable sample of foxes from Scotland and similar to that of suspected AR poisoned animals from England and Wales. High exposure in NI foxes is probably due to greater predation of commensal rodents and non-target species most likely to take AR baits, and may also partly reflect greater exposure to highly persistent brodifacoum and flocoumafen. High exposure is likely to enhance risk and Ireland may be a sentinel for potential effects on predator populations.

Analysis of the subcellular trafficking properties of murine cytomegalovirus M78, a 7 transmembrane receptor homologue.

Murine cytomegalovirus (MCMV) M78 is a member of the betaherpesvirus 'UL78 family' of seven transmembrane receptor (7TMR) genes. Previous studies of M78 and its counterpart in rat cytomegalovirus (RCMV) have suggested that these genes are required for efficient cell-cell spread of their respective viruses in tissue culture and demonstrated that gene knockout viruses are significantly attenuated for replication in vivo. However, in comparison with other CMV 7TMRs, relatively little is known about the basic biochemical properties and subcellular trafficking of the UL78 family members. We have characterized MCMV M78 in both transiently transfected and MCMV-infected cells to determine whether M78 exhibits features in common with cellular 7TMR. We obtained preliminary evidence that M78 formed dimers, a property that has been reported for several cellular 7TMR. M78 traffics to the cell surface, but was rapidly and constitutively endocytosed. Antibody feeding experiments demonstrated co-localization of M78 with markers for both the clathrin-dependent and lipid raft/caveolae-mediated internalization pathways. In MCMV-infected cells, the subcellular localization of M78 was modified during the course of infection, which may be related to the incorporation of M78 into the virion envelope during the course of virion maturation.

Rational peptide selection to detect human immunodeficiency virus type 1-specific T-cell responses under resource-limited conditions.

Understanding human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte responses is important for the development of vaccines and therapies. We describe a novel method for the rational selection of peptides that target stable regions of the HIV-1 genome, rich in epitopes specifically recognized by the study population. This method will be of particular use under resource/sample-limited conditions.

Optical performance of frequency-selective bolometers.

Frequency-selective bolometers (FSBs) are a new type of detector for millimeter and submillimeter wavelengths that are transparent to all but a narrow range of frequencies as set by characteristics of the absorber itself. Therefore stacks of FSBs tuned to different frequencies provide a low-loss compact method for utilizing a large fraction of the light collected by a telescope. Tests of prototype FSBs indicate that the absorption spectra are well predicted by models, that peak absolute absorption efficiencies of the order of 50% are attainable, and that their out-of-band transmission is high.

Coagulation of NOM: linking character to treatment.

The paper presents an overview and discussion on the link between natural organic matter (NOM) character and its treatability by coagulation. Trials were conducted on a series of bench scale and pilot plant trials on three source waters: two from UK moorland catchments and one from a US snow melt source. Overall the work demonstrates the importance of the polarity balance and the charge density of the NOM contained within the source water. The hydrophobic content controls the coagulant demand such that variation in the demand between sources or sampling periods can be accounted for by changes in the hydrophobic content and its charge density. The raw water hydrophilic content, and specifically the nonacid fraction, provides a useful indicator of the achievable residual. Analysis of coagulation performance revealed a clear relationship between zeta potential and residual DOC. For each source an operational zeta potential range exists within which the residual concentration is optimal. Comparison of the ranges achieved during each trial demonstrated that a communal range between -10 and +3 mV exist for all waters thus providing a useful guide range for operational control.

Determination of chloralose residues in animal tissues by liquid chromatography-electrospray ionisation tandem mass spectrometry.

A relatively rapid and specific method for the determination of chloralose in animal tissues by LCMSMS was developed. Isocratic reverse phase HPLC was used to introduce samples for electrospray negative ionisation tandem mass spectrometry. Methanol extracts were diluted to approximate the mobile phase composition, then filtered prior to analysis. Residues were identified by monitoring the multiple reaction monitoring (MRM) transitions of precursor ions mass:charge (m/z) 309 and 307 to a common m/z 161 product ion. Qualitative and quantitative confirmation data were acquired simultaneously by monitoring alternative MRM transitions. Calibration was linear over a working range of 0.025-1.3 microg/ml, and the limit of quantitation (LOQ) was 0.28 mg/kg for liver. The mean recovery was 88.5% from chicken muscle tissue fortified at 198-237 mg/kg, and ranged from 81.3 to 94.3% from liver tissue fortified at 1-52 mg/kg. The method is compared to a gas chromatography (GC) procedure previously employed.

Flocs through the looking glass.

The paper describes the investigation of how the make up of raw water influences the physical properties of flocculated suspensions. The work focuses on the properties of four characteristic organic fractions separated as a function of their hydrophobicity. Mesoscale data indicates that the hydrophobic fractions dominate the make up of the water and are the most easily removed. Microscale and nanoscale data reveals that the fulvic acid fraction (FAF) generates statistically smaller and more compact flocs than those formed by the other fractions and the hydrophilic fractions form the most internally open and dendritic structures. The FAF fraction was also seen to dominate the zeta potential response of the raw water.

Molecular determinants of voltage-dependent gating and binding of pore-blocking drugs in transmembrane segment IIIS6 of the Na(+) channel alpha subunit.

Mutations of amino acid residues in the inner two-thirds of the S6 segment in domain III of the rat brain type IIA Na(+) channel (G1460A to I1473A) caused periodic positive and negative shifts in the voltage dependence of activation, consistent with an alpha-helix having one face on which mutations to alanine oppose activation. Mutations in the outer one-third of the IIIS6 segment all favored activation. Mutations in the inner half of IIIS6 had strong effects on the voltage dependence of inactivation from closed states without effect on open-state inactivation. Only three mutations had strong effects on block by local anesthetics and anticonvulsants. Mutations L1465A and I1469A decreased affinity of inactivated Na(+) channels up to 8-fold for the anticonvulsant lamotrigine and its congeners 227c89, 4030w92, and 619c89 as well as for the local anesthetic etidocaine. N1466A decreased affinity of inactivated Na(+) channels for the anticonvulsant 4030w92 and etidocaine by 3- and 8-fold, respectively, but had no effect on affinity of the other tested compounds. Leu-1465, Asn-1466, and Ile-1469 are located on one side of the IIIS6 helix, and mutation of each caused a positive shift in the voltage dependence of activation. Evidently, these amino acid residues face the lumen of the pore, contribute to formation of the high-affinity receptor site for pore-blocking drugs, and are involved in voltage-dependent activation and coupling to closed-state inactivation.

Inhibition of cardiac L-type calcium channels by protein kinase C phosphorylation of two sites in the N-terminal domain.

We have investigated the mechanism underlying the modulation of the cardiac L-type Ca(2+) current by protein kinase C (PKC). Using the patch-clamp technique, we found that PKC activation by 4-alpha-phorbol 12-myristate 13-acetate (PMA) or rac-1-oleyl-2-acetylglycerol (OAG) caused a substantial reduction in Ba(2+) current through Ca(v)1.2 channels composed of alpha(1)1.2, beta(1b), and alpha(2)delta(1) subunits expressed in tsA-201 cells. In contrast, Ba(2+) current through a cloned brain isoform of the Ca(v)1.2 channel (rbC-II) was unaffected by PKC activation. Two potential sites of PKC phosphorylation are present at positions 27 and 31 in the cardiac form of Ca(v)1.2, but not in the brain form. Deletion of N-terminal residues 2-46 prevented PKC inhibition. Conversion of the threonines at positions 27 and 31 to alanine also abolished the PKC sensitivity of Ca(v)1.2. Mutant Ca(v)1.2 channels in which the threonines were converted singly to alanines were also insensitive to PKC modulation, suggesting that phosphorylation of both residues is required for PKC-dependent modulation. Consistent with this, mutating each of the threonines individually to aspartate in separate mutants restored the PKC sensitivity of Ca(v)1.2, indicating that a change in net charge by phosphorylation of both sites is responsible for inhibition. Our results define the molecular basis for inhibition of cardiac Ca(v)1.2 channels by the PKC pathway.

A quadricuspid pulmonic valve diagnosed in a live newborn by two-dimensional echocardiography.

Quadricuspid pulmonic valve is a rare congenital anomaly which appears to occur in the absence of other cardiac or systemic anomalies. It predominates in males and tends to be clinically quiescent. The first case of quadricuspid pulmonic valve in a live newborn infant diagnosed by two-dimensional echocardiography is presented here with a review of the literature.