Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Lower-extremity muscle atrophy and fat infiltration after chronic spinal cord injury.

BACKGROUND: Atrophy and fatty-infiltration of lower-extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic disease and related mortality. OBJECTIVES: To determine the magnitude of atrophy and fatty-infiltration of lower-extremity muscles and related factors in a group of individuals with chronic SCI and diverse impairment. METHODS: Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf of 70 participants with chronic SCI [50 male, mean age 49 (standard deviation 12) years, C2-T12, AIS A-D] and matched controls. Regression models for muscle area and density were formed using 16 potential correlates selected a priori. RESULTS: Participants with motor-complete SCI had ≈ 32% lower muscle area, and ≈ 43% lower muscle density values relative to controls. Participants with motor-incomplete SCI had muscle area and density values that were both ≈ 14% lower than controls. Body mass (+), tetraplegia (+), motor function (+), spasticity (+), vigorous physical activity (+), wheelchair use (-), age (-), and waist circumference (-) were associated with muscle size and/or density in best-fit regression models. CONCLUSIONS: There are modifiable factors related to muscle size, body composition, and activity level that may offer therapeutic targets for preserving metabolic health after chronic SCI.

Boson sampling from a Gaussian state.

We pose a randomized boson-sampling problem. Strong evidence exists that such a problem becomes intractable on a classical computer as a function of the number of bosons. We describe a quantum optical processor that can solve this problem efficiently based on a Gaussian input state, a linear optical network, and nonadaptive photon counting measurements. All the elements required to build such a processor currently exist. The demonstration of such a device would provide empirical evidence that quantum computers can, indeed, outperform classical computers and could lead to applications.

Reference-frame-independent quantum-key-distribution server with a telecom tether for an on-chip client.

We demonstrate a client-server quantum key distribution (QKD) scheme. Large resources such as laser and detectors are situated at the server side, which is accessible via telecom fiber to a client requiring only an on-chip polarization rotator, which may be integrated into a handheld device. The detrimental effects of unstable fiber birefringence are overcome by employing the reference-frame-independent QKD protocol for polarization qubits in polarization maintaining fiber, where standard QKD protocols fail, as we show for comparison. This opens the way for quantum enhanced secure communications between companies and members of the general public equipped with handheld mobile devices, via telecom-fiber tethering.

Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation.

Regulatory T cell (Treg) therapy has the potential to induce transplantation tolerance so that immunosuppression and associated morbidity can be minimized. Alloantigen-reactive Tregs (arTregs) are more effective at preventing graft rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have developed a manufacturing process to expand human arTregs in short-term cultures using good manufacturing practice-compliant reagents. This process uses CD40L-activated allogeneic B cells to selectively expand arTregs followed by polyclonal restimulation to increase yield. Tregs expanded 100- to 1600-fold were highly alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen-expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model.

Prevalence and specificity of red-blood-cell antibodies in a multiethnic South and East Asian patient population and influence of using novel MUT+Mur+ kodecytes on its detection.

BACKGROUND AND OBJECTIVES: Appropriate screening for irregular red-cell antibodies is essential for ensuring transfusion compatibility and for antenatal management of mothers at risk of haemolytic disease of the foetus and newborn. Screening for all relevant antibodies is, however, limited by screening cells that do not express antigens present in the patient and donor population. Technology to artificially incorporate antigens into red cells is currently available and may be an option for customizing screening cells. MATERIALS AND METHODS: We sought to identify retrospectively the changing patterns of alloantibody prevalence in our multiethnic population on change of screening cells. Antibody screening records of 143 501 patients tested from 2004 to 2010 were retrieved and divided into two groups: period-1 (2004-2008) and period-2 (2009-2010). During period-1, standard screening cells were used while in period-2, MUT+Mur+ KODE(™) transformed red cells (kodecytes) were used. RESULTS: Four per cent of samples tested during period-2 were positive on antibody screening compared to 3·2% in period-1. Specific antibodies, excluding anti-D, were identified in 1·66% and 1·52% of patients in period-2 and -1, respectively. When confined to antibodies of clinical significance only, period-2 showed higher alloantibody prevalence of 1·16% as compared to 0·66% in period-1. Antibodies to glycophorin variants of MNS (vMNS) were more commonly detected while antibodies to Lewis antigens declined during period-2. CONCLUSION: Antibodies to vMNS antigens are common in South and East Asian populations and are often missed when using standard screening cells. Use of specifically engineered screening cells to express red-cell antigens artificially is beneficial in detecting the diverse alloantibodies present in our population.

An optical neural chip for implementing complex-valued neural network.

Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle and Spiral), and handwriting recognition. Strong learning capabilities (i.e., high accuracy, fast convergence and the capability to construct nonlinear decision boundaries) are achieved by our complex-valued ONC compared to its real-valued counterpart.

Convergent evolution of pain-inducing defensive venom components in spitting cobras.

Convergent evolution provides insights into the selective drivers underlying evolutionary change. Snake venoms, with a direct genetic basis and clearly defined functional phenotype, provide a model system for exploring the repeated evolution of adaptations. While snakes use venom primarily for predation, and venom composition often reflects diet specificity, three lineages of cobras have independently evolved the ability to spit venom at adversaries. Using gene, protein, and functional analyses, we show that the three spitting lineages possess venoms characterized by an up-regulation of phospholipase A2 (PLA2) toxins, which potentiate the action of preexisting venom cytotoxins to activate mammalian sensory neurons and cause enhanced pain. These repeated independent changes provide a fascinating example of convergent evolution across multiple phenotypic levels driven by selection for defense.

Hip protectors: recommendations for conducting clinical trials--an international consensus statement (part II).

INTRODUCTION: While hip protectors are effective in some clinical trials, many, including all in community settings, have been unable to demonstrate effectiveness. This is due partly to differences in the design and analysis. The aim of this report is to develop recommendations for subsequent clinical research. METHODS: In November of 2007, the International Hip Protector Research Group met to address barriers to the clinical effectiveness of hip protectors. This paper represents a consensus statement from the group on recommended methods for conducting future clinical trials of hip protectors. RESULTS AND CONCLUSIONS: Consensus recommendations include the following: the use of a hip protector that has undergone adequate biomechanical testing, the use of sham hip protectors, the conduct of clinical trials in populations with annual hip fracture incidence of at least 3%, a run-in period with demonstration of adequate adherence, surveillance of falls and adherence, and the inclusion of economic analyses. Larger and more costly clinical trials are required to definitively investigate effectiveness of hip protectors.

Multimodality treatment of intracranial arteriovenous malformations in South Island, New Zealand.

Treatment of intracranial arteriovenous malformations is complex and multidisciplinary. This article presents the treatment model utilized in Christchurch, New Zealand which provides cerebrovascular surgery and interventional neuroradiology to the entire south island (approximate population of 1.1 million). A total of 40 patients treated over a 10 year period (2004-2014) are analysed here. Nine patients were managed surgically and complete resection was achieved in 100% of cases. Permanent mortality was 0% and permanent morbidity was 22% however median mRS improved from 3.0 preoperatively to 1.0 at follow up. Embolisation was utilized in 31 patients (mean age 40), of which 45% presented with haemorrhage, 39% with seizures, 10% with a headache only, and 6% with a deficit. None were found incidentally. The Spetzler-Martin grade 1 cases accounted for 10% of the cohort, 23% were grade II, 42% grade III, 23% grade IV and 3% grade V. A single aneurysm was present in 42% of cases, and multiple in 13%. The nidus was obliterated in 9.6% of cases with a morbidity rate of 6.5% and mortality rate of 3%. Modified Rankin scale improved marginally from 0.9 at diagnosis to 0.88 at final follow up (mean 22 months). There were no cases of recanalization. The total nidus obliteration rate using our algorithm of surgery alone for small accessible lesions, then staged embolization for larger lesions with adjuvant radiosurgery reserved for cases with residual nidus, was 50%.

Near-ideal spontaneous photon sources in silicon quantum photonics.

While integrated photonics is a robust platform for quantum information processing, architectures for photonic quantum computing place stringent demands on high quality information carriers. Sources of single photons that are highly indistinguishable and pure, that are either near-deterministic or heralded with high efficiency, and that are suitable for mass-manufacture, have been elusive. Here, we demonstrate on-chip photon sources that simultaneously meet each of these requirements. Our photon sources are fabricated in silicon using mature processes, and exploit a dual-mode pump-delayed excitation scheme to engineer the emission of spectrally pure photon pairs through inter-modal spontaneous four-wave mixing in low-loss spiralled multi-mode waveguides. We simultaneously measure a spectral purity of 0.9904 ± 0.0006, a mutual indistinguishability of 0.987 ± 0.002, and  >90% intrinsic heralding efficiency. We measure on-chip quantum interference with a visibility of 0.96 ± 0.02 between heralded photons from different sources.

Perinatal inflammation influences but does not arrest rapid immune development in preterm babies.

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this risk, there is limited understanding of the development of the immune system in those born prematurely, and of how this development is influenced by perinatal factors. Here we prospectively and longitudinally follow a cohort of babies born before 32 weeks of gestation. We demonstrate that preterm babies, including those born extremely prematurely (<28 weeks), are capable of rapidly acquiring some adult levels of immune functionality, in which immune maturation occurs independently of the developing heterogeneous microbiome. By contrast, we observe a reduced percentage of CXCL8-producing T cells, but comparable levels of TNF-producing T cells, from babies exposed to in utero or postnatal infection, which precedes an unstable post-natal clinical course. These data show that rapid immune development is possible in preterm babies, but distinct identifiable differences in functionality may predict subsequent infection mediated outcomes.

Hip protectors: recommendations for biomechanical testing--an international consensus statement (part I).

INTRODUCTION: Hip protectors represent a promising strategy for preventing fall-related hip fractures. However, clinical trials have yielded conflicting results due, in part, to lack of agreement on techniques for measuring and optimizing the biomechanical performance of hip protectors as a prerequisite to clinical trials. METHODS: In November 2007, the International Hip Protector Research Group met in Copenhagen to address barriers to the clinical effectiveness of hip protectors. This paper represents an evidence-based consensus statement from the group on recommended methods for evaluating the biomechanical performance of hip protectors. RESULTS AND CONCLUSIONS: The primary outcome of testing should be the percent reduction (compared with the unpadded condition) in peak value of the axial compressive force applied to the femoral neck during a simulated fall on the greater trochanter. To provide reasonable results, the test system should accurately simulate the pelvic anatomy, and the impact velocity (3.4 m/s), pelvic stiffness (acceptable range: 39-55 kN/m), and effective mass of the body (acceptable range: 22-33 kg) during impact. Given the current lack of clear evidence regarding the clinical efficacy of specific hip protectors, the primary value of biomechanical testing at present is to compare the protective value of different products, as opposed to rejecting or accepting specific devices for market use.

Mobilization of endothelial precursor cells: systemic vascular response to musculoskeletal trauma.

Postnatal vasculogenesis, the process by which vascular committed bone marrow stem cells or endothelial precursor cells (EPC) migrate, differentiate, and incorporate into the nacent endothelium contributing to physiological and pathological neovascularization, has stimulated much interest. Its contribution to tumor nonvascularization, wound healing, and revascularization associated with skeletal and cardiac muscles ischaemia is established. We evaluated the mobilization of EPCs in response to musculoskeletal trauma. Blood from patients (n = 15) following AO type 42a1 closed diaphyseal tibial fractures was analyzed for CD34 and AC133 cell surface marker expression. Immunomagnetically enriched CD34+ mononuclear cell (MNC(CD34+)) populations were cultured and examined for phenotypic and functional vascular endothelial differentiation. Circulating MNC(CD34+) levels increased sevenfold by day 3 postinjury. Circulating MNC(AC133+) increased 2.5-fold. Enriched MNC(CD34+) populations from day 3 samples in culture exhibited cell cluster formation with sprouting spindles. These cells bound UEA-1 and incorporated fluorescent DiI-Ac-LDL intracellularily. Our findings suggest a systemic provascular response is initiated in response to musculoskeletal trauma. Its therapeutic manipulation may have implications for the potential enhancement of fracture healing.

E7 (1057ΔTA) mutation of the acidic α-glucosidase gene causes Pompe's disease in Droughtmaster cattle.

OBJECTIVE: To determine whether known loss-of-function alleles of the acidic α-glucosidase gene (GAA) are present in the Droughtmaster breed and, if so, whether the clinical signs and pathology of generalised glycogenosis (Pompe's disease) previously reported in other affected cattle are also seen in homozygous Droughtmasters. DESIGN: Existing genomic and other diagnostic tests developed for generalised glycogenosis in cattle were used to test for the presence of the three known loss-of-function alleles of GAA in a herd of Droughtmaster cattle. Two calves with clinical signs of generalised glycogenosis were submitted for necropsy. RESULTS: One loss-of-function GAA mutation (1057ΔTA or E7 allele) was identified using SNP chip technology and confirmed using conventional diagnostic DNA tests. Further testing demonstrated that the mutation was common within this herd and that two ill-thrift calves were homozygous for the E7 allele. Parentage analysis confirmed both sire and dam as heterozygous carriers. Pathology consistent with generalised glycogenosis was found in the skeletal and cardiac muscle and spinal cord of both of the affected calves. The 1783C>T (E13) or 2454ΔCA (E18) mutations associated with generalised glycogenosis in the Brahman and Shorthorn breeds, respectively, were not detected. CONCLUSION: The lethal mutation 1057ΔTA of GAA is present in the Droughtmaster breed, with pathology identical to that reported in pure Brahman animals. Droughtmaster breeders should take action to prevent any increase in the prevalence of this lethal allele in the breed as it could cause both welfare issues and production losses if ignored.

Volar dislocation of the index carpometacarpal joint in association with a Bennett's fracture of the thumb: a rare injury pattern.

We describe a case of volar dislocation of the index carpometacarpal (CMC) joint in association with a Bennett's fracture of the thumb following a motorcycle accident. Volar dislocation of the index carpometacarpal joint is an exceedingly rare but easily missed injury, with only a few reported cases in the literature. This report highlights the importance of a true lateral radiograph and close scrutiny of the film to detect this injury. Closed reduction supplemented with Kirschner wire fixation restored normal anatomical relations and achieved an excellent clinical result.

The impact of ice-skating injuries on orthopaedic admissions in a regional hospital.

Since the opening of a temporary ice-rink in our hospital's catchment area, we have observed an increase in patients requiring in-patient treatment for orthopaedic intervention. The authors performed a prospective analysis of all patients admitted to our unit over a one-month period. Epidemiological data, wearing of protective gear and skater experience were collected. Fracture type, treatment required, average length of hospital stay and number of days missed from work was also recorded. Ice-skating injuries accounted for 7.7% of our total admissions over the study period. There was a significant variation noted in the types of fracture sustained ranging from comminuted fractures of the radial head to spiral fractures of the tibia. The average length of hospital stay was 2.6 days and average time missed from work was 6.1 weeks. This paper highlights the potential serious injuries that can occur in ice-skating and their impact on admissions to our orthopaedic unit.

Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

The effects of oestrogen administration on tryptophan metabolism in rats and in menopausal women receiving hormone replacement therapy.

The effects of the administration of oestrogens on the activity of hepatic tryptophan oxygenase have been assessed both directly (by measurement of enzyme activity in vitro) and indirectly (by measurement of urinary excretion of tryptophan metabolites) in rats, and indirectly in menopausal women receiving hormone replacement therapy. Intraperitoneal administration of 500 micrograms of oestradiol or ethinyl oestradiol/kg body wt had no effect on the activity of tryptophan oxygenase in homogenates of liver from mature (13-week-old) female rats. Both adrenalectomy and ovariectomy led to a reduction in the activity of tryptophan oxygenase in homogenates of liver from mature rats; again there was no effect of giving 500 micrograms of oestradiol/kg body wt by intraperitoneal injection. Intraperitoneal administration of 210 micrograms of oestrone sulphate/kg body wt for 1 or 2 days before killing, or its incorporation in the diet for up to 8 weeks at an equivalent dose rate, had no effect on the activity of tryptophan oxygenase in homogenates of liver from ovariectomized 6-14-week-old female rats. Intraperitoneal administration of 500 micrograms oestradiol/kg body wt to intact mature female rats together with 500 mg tryptophan/kg body wt caused a reduction in the urinary excretion of xanthurenic and kynurenic acids, kynurenine and N1-methyl nicotinamide. When peri- and post-menopausal women were treated with ethinyl oestradiol (20 micrograms/day) or piperazine oestrone sulphate (3 mg/day) for 3 months, there was an increase in the concn of tryptophan in plasma, with no change in the urinary excretion of xanthurenic and kynurenic acids and kynurenine. This study provides no evidence for the induction of tryptophan oxygenase by oestrogens in rats or human beings.

The effect of acute hypoglycemia on the cerebral NMDA receptor in newborn piglets.

The effects of acute insulin-induced hypoglycemia on the cerebral NMDA receptor in the newborn were examined by determining [3H]MK-801 binding as an index of NMDA receptor function in 6 control and 7 hypoglycemic piglets. In hypoglycemic animals, the glucose clamp technique with constant insulin infusion was used to maintain a blood glucose concentration of 1.2 mmol/l for 120 min before obtaining cerebral cortex for further analysis; controls received a saline infusion. Concentrations of glucose, lactate, ATP, and PCr were measured in cortex, and Na+,K(+)-ATPase activity was determined in a brain cell membrane preparation. [3H]MK-801 binding was evaluated by: (1) saturation binding assays over the range of 0.5-50 nM [3H]MK-801 in the presence of 100 microM glutamate and glycine; and (2) binding assays at 10 nM [3H]MK-801 in the presence of glutamate and/or glycine at 0, 10, or 100 microM. Blood and brain glucose concentrations were significantly lower in hypoglycemic animals than controls. There was no change in brain ATP with hypoglycemia, but PCr was decreased 80% compared to control (P < 0.05). Na+,K(+)-ATPase activity was 13% lower in hypoglycemic animals (P < 0.05). Based on saturation binding data, hypoglycemia had no effect on the number of functional receptors (Bmax), but the apparent affinity was significantly increased, as indicated by a decrease in the Kd (dissociation constant) from the control value of 8.1 +/- 1.6 nM to 5.5 +/- 2.1 nM (P < 0.05). Augmentation of [3H]MK-801 binding by glutamate and glycine alone or in combination was also significantly greater in the hypoglycemic animals.(ABSTRACT TRUNCATED AT 250 WORDS)