Materials loss measurements using superconducting microwave resonators.

The performance of superconducting circuits for quantum computing is limited by materials losses. In particular, coherence times are typically bounded by two-level system (TLS) losses at single photon powers and millikelvin temperatures. The identification of low loss fabrication techniques, materials, and thin film dielectrics is critical to achieving scalable architectures for superconducting quantum computing. Superconducting microwave resonators provide a convenient qubit proxy for assessing performance and studying TLS loss and other mechanisms relevant to superconducting circuits such as non-equilibrium quasiparticles and magnetic flux vortices. In this review article, we provide an overview of considerations for designing accurate resonator experiments to characterize loss, including applicable types of losses, cryogenic setup, device design, and methods for extracting material and interface losses, summarizing techniques that have been evolving for over two decades. Results from measurements of a wide variety of materials and processes are also summarized. Finally, we present recommendations for the reporting of loss data from superconducting microwave resonators to facilitate materials comparisons across the field.

Freshwater movement patterns by juvenile Pacific salmon Oncorhynchus spp. before they migrate to the ocean: Oh the places you'll go!

Juvenile movement patterns for coho salmon Oncorhynchus kisutch and Chinook salmon Oncorhynchus tshawytscha from two large interior rivers of British Columbia, Canada, were examined. Otoliths from post-spawned fishes were collected on spawning grounds and elemental signatures were determined through transects from sectioned otoliths using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Large variations in otolith elemental signatures were found during the freshwater life stage indicative of movement downstream to rivers and tributaries that differed in elemental signature. This study highlights that downstream movements occur before migration to the ocean during the parr-smolt transformation. Extensive downstream movements of parr appear to be a successful life-history strategy based on variations observed in the otolith elemental signatures of spawners. Movements downstream in parr and the remarkable homing ability of adults also suggest that imprinting to natal streams must occur prior to the parr-smolt transformation.

Metabolite Profiling in the Pursuit of Biomarkers for IVF Outcome: The Case for Metabolomics Studies.

Background. This paper presents the literature on biomarkers of in vitro fertilisation (IVF) outcome, demonstrating the progression of these studies towards metabolite profiling, specifically metabolomics. The need for more, and improved, metabolomics studies in the field of assisted conception is discussed. Methods. Searches were performed on ISI Web of Knowledge SM for literature associated with biomarkers of oocyte and embryo quality, and biomarkers of IVF outcome in embryo culture medium, follicular fluid (FF), and blood plasma in female mammals. Results. Metabolomics in the field of female reproduction is still in its infancy. Metabolomics investigations of embryo culture medium for embryo selection have been the most common, but only within the last five years. Only in 2012 has the first metabolomics investigation of FF for biomarkers of oocyte quality been reported. The only metabolomics studies of human blood plasma in this context have been aimed at identifying women with polycystic ovary syndrome (PCOS). Conclusions. Metabolomics is becoming more established in the field of assisted conception, but the studies performed so far have been preliminary and not all potential applications have yet been explored. With further improved metabolomics studies, the possibility of identifying a method for predicting IVF outcome may become a reality.

Understanding subfertility at a molecular level in the female through the application of nuclear magnetic resonance (NMR) spectroscopy.

BACKGROUND: Understanding the aetiology of subfertility and female reproductive tract disorders at a molecular level may improve success rates in fertility treatment. Such understanding may be gained by the application of metabonomics technologies to tissues or biofluids. Metabonomics is concerned with the quantification of molecules in the metabolome and uses nuclear magnetic resonance (NMR) spectroscopy as one of the main technological platforms. This review concentrates on NMR studies of the female reproductive tract and discusses further possible applications. While full metabolic profiling is relatively recent, targeted NMR studies of biofluid and tissue has a longer history. METHODS: Searches were carried out on MEDLINE(®), PubMed, SciFinder(®) Scholar 2007 and ISI Web of Knowledge(SM) for papers about NMR spectroscopy or metabonomics of the female reproductive tract and subfertility. RESULTS: NMR spectroscopy has been employed for the compositional analysis of various elements of the female reproductive tract, including cervical mucus, follicular fluid (FF), ovarian tissue, fallopian tubes and uterine matter. NMR was used to document for the first time a change in FF lipoprotein concentration during follicular development. NMR analysis of granulosa cells from rats has revealed that follicle-stimulating hormone increases the activity of the pentose pathway, having crucial implications for ovarian stimulation regimens. In the uterine matter work, it has been shown by NMR that glycolysis is rapidly stimulated by estrogen, and in another study, citrate in uterine fluid was found as a potential biomarker for adenomyosis. NMR has also been used to show that chlamydiae are able to achieve higher energy reserves by stimulating glucose transport in host cells. CONCLUSIONS: A range of NMR spectroscopic techniques have been applied to the analysis of the female reproductive tract, however great potential remains for further studies. Incorporation of metabonomics techniques into female fertility research may be valuable for understanding subfertility and predicting outcomes of assisted conception treatments.

Both isoforms of ketohexokinase are dispensable for normal growth and development.

Dietary fructose intake has dramatically increased over recent decades and is implicated in the high rates of obesity, hypertension, and type 2 diabetes (metabolic syndrome) in Western societies. The molecular determinants of this epidemiologic correlation are incompletely defined, but high-flux fructose catabolism initiated by ketohexokinase (Khk, fructokinase) is believed to be important. The Khk gene encodes two enzyme isoforms with distinctive substrate preferences, the independent physiological roles of which are unclear. To investigate this question, and for testing the importance of Khk in metabolic syndrome, isoform-selective genetic lesions would be valuable. Two deficiency alleles of the mouse Khk gene were designed. The first, Khk(3a), uses targeted "knock-in" of a premature termination codon to induce a selective deficiency of the minor Khk-A isoform, preserving the major Khk-C isoform. The second, the Khk(Δ) allele, ablates both isoforms. Mice carrying each of these Khk-deficiency alleles were generated and validated at the DNA, RNA, and protein levels. Comparison between normal and knockout animals confirmed the specificity of the genetic lesions and allowed accurate analysis of the cellular distribution of Khk within tissues such as gut and liver. Both Khk(3a/3a) and Khk(Δ/Δ) homozygous mice were healthy and fertile and displayed minimal biochemical abnormalities under basal dietary conditions. These studies are the first demonstration that neither Khk isoform is required for normal growth and development. The new mouse models will allow direct testing of various hypotheses concerning the role of this enzyme in metabolic syndrome in humans and the value of Khk as a pharmacological target.

Cycling for children with neuromuscular impairments using electrical stimulation--development of tricycle-based systems.

AIM: Cycling using functional electrical stimulation (FES-cycling) is a well defined exercise method for adults with spinal cord injury (SCI). Although little studied thus far, FES-cycling also has the potential to offer a means of exercise to pediatric populations, such as SCI or cerebral palsy (CP), that presently have few alternative options. The primary aim of this study was to develop FES-cycling equipment and methods which can meet the differing needs of children with SCI and CP. METHODS: Design criteria were determined based on key considerations for pediatric FES-cycling. Two separate prototype systems for training/recreation and laboratory-based research were built to meet these specifications. To experimentally verify the equipment, FES-cycling tests involving one child with motor complete SCI and one child with diplegic spastic CP were performed using the laboratory system. RESULTS: Experimental verification indicated that FES-cycling experiments involving children with SCI and CP are feasible provided that accurate measurement of both propulsive and resistive torque is achieved. Specific seating and orthotic needs for each subject population were met by both systems. CONCLUSION: The FES-cycling systems described here may assist in future investigations of pediatric FES-cycling performance and novel exercise regimes designed specifically for children.

Early and pre-symptomatic neuropsychological dysfunction in the PPND family with the N279K tau mutation.

The N279K mutation on the tau gene of chromosome 17 leads to an inherited condition that involves pallido-ponto-nigral degeneration (PPND). Patients with PPND develop dementia, but the pattern and onset of cognitive dysfunction has not yet been delineated. Four affected patients underwent neurocognitive evaluation within the first 2 years of PPND motor onset; one of whom underwent five serial neurocognitive evaluations, and another who was not diagnosed with PPND until the third annual evaluation. Impaired letter fluency was found in the early stages of PPND and was also shown to precede the onset of motor symptoms by 2 years. Trail Making A (visual scanning and motor speed) and Trail Making B (divided attention) were impaired within the first 2 years of the disease in all but one patient, but this individual showed clinically significant decline on these tasks by the third year of the disease. Learning, memory, and timed visuospatial sequencing skills were variably affected. Results reveal disproportionate frontal-executive dysfunction early in PPND disease course, a pattern similar to what has been reported in other FTDP-17 kindreds and in sporadic PSP. In addition, results suggest that letter fluency may be a sensitive predictor of incipient PPND.

Hepatitis associated with Chinese herbs.

Traditional Chinese herbal medicines are widely available in Western society and are popular as a form of 'natural' alternative medicine. Their use is increasing, as they are perceived to be free of side effects, but they remain largely unregulated. We describe two patients who suffered severe hepatitis, one of whom died, after taking Chinese herbal remedies for minor complaints. We also review the English-language literature on hepatitis associated with Chinese herbs. Two products appear to be implicated frequently: Jin bu huan was taken by 11 patients, and Dictamnus dasycarpus was taken by six patients, including both fatal cases. It is difficult to provide conclusive evidence of what caused hepatitis, as these products are mixtures that may contain adulterants. These cases highlight not only the potential dangers of these products to consumers but also the need for greater control of their manufacture and use.

Interest in genetic testing in pallido-ponto-nigral degeneration (PPND): a family with frontotemporal dementia with Parkinsonism linked to chromosome 17.

The specific mutation on the tau gene responsible for a neurodegenerative disease known as pallido-ponto-nigral degeneration (PPND) was recently located. PPND family members are at risk for an autosomal dominant form of frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). This study investigated whether individuals in this family would consider presymptomatic genetic testing. Surveys were sent to 66 at-risk individuals in the family; replies were received from 20 (30%). Family members were asked if they would consider having testing now or in the future, and to indicate their reasons for and against proceeding with testing. Fifty per cent (n=10) of those who were at risk and who responded indicated they would consider testing now, and 55% (n=11) would think about it in the future. The most frequently cited reasons to proceed with testing were to 'collaborate with research' (70%) and to 'know if my children are at risk' (45%). The most frequently cited reason not to pursue testing was 'I can enjoy my life more fully by not knowing' (50%). Results suggest that interest in determining whether they will manifest PPND is generally low among at-risk members of this family, despite wide support and participation in other research studies.

Height-related risk factors for prostate cancer.

Previous studies have reported that adult height is positively associated with the risk of prostate cancer. The authors carried out a population-based case-control study involving 317 prostate cancer cases and 480 controls to further investigate the possibility that height is more strongly associated with advanced, compared with localized forms of this disease. Since the inherited endocrine factors, which in part determine height attained during the growing years, may influence the risk of familial prostate cancer later in life, the relationship with height was also investigated for familial versus sporadic prostate cancers. Adult height was not related to the risk of localized prostate cancer, but there was a moderate positive association between increasing height and the risk of advanced cancer (relative risk (RR) = 1.62; 95% confidence interval (CI) 0.97-2.73, upper versus lowest quartile, P-trend = 0.07). Height was more strongly associated with the risk of prostate cancer in men with a positive family history compared with those reporting a negative family history. The RR of advanced prostate cancer for men in the upper height quartile with a positive family history was 7.41 (95% CI 1.68-32.67, P-trend = 0.02) compared with a reference group comprised of men in the shortest height quartile with a negative family history. Serum insulin-like growth factor-1 levels did not correlate with height amongst men with familial or sporadic prostate cancers. These findings provide evidence for the existence of growth-related risk factors for prostate cancer, particularly for advanced and familial forms of this disease. The possible existence of inherited mechanisms affecting both somatic and tumour growth deserves further investigation.

A population-based study of clinical and pathological prognostic characteristics of men with familial and sporadic prostate cancer.

OBJECTIVES: To compare traditional prognostic characteristics of familial vs sporadic prostate cancers and to investigate potential detection biases arising from differences in the use of screening and investigative procedures. PATIENTS AND METHODS: Familial and sporadic cancers were identified in a population-based sample of incident prostate cancers (total 318) in Auckland, New Zealand. To examine the potential for detection biases in these comparisons, the sociodemographic and clinical characteristics were determined according to family history status for a sample of 959 patients newly referred to Auckland urology clinics by general practitioners for the investigation of prostate-related conditions. RESULTS: Compared with sporadic prostate cancers, familial cancers were more likely to be diagnosed in patients at a younger age (P=0.05), after asymptomatic serum prostate-specific antigen (PSA) screening (P=0. 02), and to include a lower proportion with extraprostatic disease (P=0.009) and serum PSA levels before diagnosis of >20 ng/mL (P=0. 04). This was consistent with the observed trend for patients referred to urology clinics with a positive family history to be of higher socio-economic and educational status and to more frequently undergo screening and biopsy investigation. CONCLUSION: Familial prostate cancers appeared to be diagnosed at an earlier stage of disease progression in this study population, possibly as the result of the higher socio-economic status and greater use of screening and investigative procedures amongst patients reporting a positive family history. These features reduce the validity of cross-sectional comparisons of prognostic variables for familial vs sporadic prostate cancer and emphasize the need for further longitudinal prognostic studies.

Stress and family functioning among caregivers of persons with Parkinson's disease.

This study investigated components of caregiving that cause distress among Parkinson's caregivers and explored relationships between stress and family functioning. Fifty caregivers completed two self-report measures designed to assess caregiver stress and characteristics of the family environment. Differences in terms of family environment were found between caregivers who reported high and low stress. Certain aspects of caregiving were reported to be more distressing than others, and demographic characteristics were related to family functioning. Duration of the caregiving was not related to stress and there were no differences in family environment based on duration. These results have implications for clinical practice and the development of interventions for Parkinson's caregivers.

Non-steroidal anti-inflammatory drugs and prostate cancer progression.

Experimental studies have suggested that the biosynthesis of arachidonic acid-derived eicosanoids such as prostaglandin E2 via the cyclo-oxygenase pathway may play a significant role in supporting cell proliferation in human prostate cancer cell lines. However, the aetiological significance of this for clinical prostate cancer has remained unclear. In particular, the potential for prostate cancer chemoprevention using nonsteroidal anti-inflammatory drugs (cyclo-oxygenase inhibitors; NSAIDs) has received little attention. The purpose of our study was to investigate associations between prostate cancer risk and use of NSAIDs. A population-based case-control study was carried out over 13 months from 1996 in metropolitan Auckland, New Zealand. A total of 317 newly diagnosed prostate cancer cases (including 192 "advanced" cases) representative of all cancer cases in the study population were identified from urology clinic referrals and histology reports. A total of 480 age-matched controls were recruited following random selection from the study population using electoral rolls as the sampling frame. After adjusting for potential confounding by socio-economic status and dietary fat consumption, there was a trend toward reduced risks of advanced prostate cancer associated with regular use of total NSAIDs (RR = 0.73; 95% CI 0.50-1.07) and total aspirin (RR = 0.71; 95% CI 0.47-1.08). However, these associations failed to reach statistical significance at the usually accepted levels. Weaker inverse associations were found for total prostate cancers, which included a number of small, low-grade tumours of less clinical significance. These findings lend support to proposed underlying aetiological hypotheses which imply a role for cyclo-oxygenase activity in prostate cancer progression.

Prostate cancer mortality in New Zealand: the past and projections for the future.

BACKGROUND: Ageing male populations and improved diagnosis of early stage disease have contributed to the increasing incidence of prostate cancer observed in many Western countries. The clinical significance of these diagnosed cancers is, however, currently unclear. The aim of this study is to examine trends over time in prostate cancer mortality as an indicative measure of clinically significant disease during a 29-year period (1965-93) which preceded the extensive use of early cancer diagnostic techniques or radical therapy protocols. METHODS: Age-specific and age-standardized rates were calculated for each year during the study period, using routinely collected mortality and demographic data. A Poisson regression model was used to describe trends in the age-specific rates over time to predict numbers of prostate cancer deaths and the lifetime risk of death over the next 20 years. RESULTS: Significant annual increases ranging from 1 to 2.6% were found for age-specific prostate cancer mortality rates over the 29-year time period, with the largest increases experienced in the younger age groups at risk. Based on projected population ageing and growth alone, annual numbers of prostate cancer deaths are predicted to increase from 487 in 1993 to 664 by the year 2006 and then to 833 by the year 2016. Continuation of the observed increases in age-specific mortality rates would result in a predicted 797 deaths by the year 2006, while an expected 1115 deaths is calculated for the year 2016. This would correspond with an increase in the lifetime risk of death from prostate cancer from a present 3.7 to 4.5% in 10 years and 6.2% in 20 years. CONCLUSIONS: The changing pattern of prostate cancer mortality described in this study is likely to represent a significant increase in the incidence of clinically significant disease. This will have a significant impact on the ageing New Zealand male population, and important implications for the provision of effective treatment and preventive strategies.

Carcinoma in situ of the testis followed by an overt malignant teratoma of the testis within 12 months.

A case of bilateral metachronous testicular non-seminomatous germ cell tumour (NSGCT) is presented. The second tumour was preceded by carcinoma in situ, diagnosed at the time of the first orchidectomy. The patient was placed under active surveillance and 1 year later the second testis tumour developed. A second orchidectomy was performed and testosterone replacement begun. Carcinoma in situ of the testis is discussed.

Clam cystoplasty for the overactive bladder: a review of 23 cases.

A clam enterocystoplasty was performed for refractory urge incontinence due to either idiopathic instability (13 patients) or neuropathic hyperreflexia (10 patients). Twelve patients became dry and appliance free. Of the remaining 11 wet patients, seven developed low pressure reservoirs, of whom five had stress incontinence and two had overflow incontinence. The other four patients had persistent symptomatic involuntary phasic contractions and ongoing urge incontinence. The magnitude of the surgery and the voiding dysfunction associated with the relative lack of motivation of elderly patients made the operation less successful and more hazardous in those over the age of 65. Successful outcome could be improved by careful patient selection and by performing an antistress incontinence procedure, such as implantation of an artificial urinary sphincter cuff or a cystourethropexy, where there is associated bladder outlet incompetence.

Failure of the porous-coated anatomic prosthesis in total knee arthroplasty due to severe polyethylene wear.

Four hundred and eighty-seven total knee arthroplasties were performed by a single surgeon with use of a porous-coated anatomic prosthesis between 1982 and 1989. There were thirty-two clinical failures (7 per cent) due to severe wear of the surfaces of the tibial and patellar polyethylene components. Thirty patients had a revision. The average time to failure of the implant was four and one-half years. The initial clinical symptoms of failure by wear consisted of a painless effusion with a decreased range of motion. Subsequent pain was considered as the criterion for failure necessitating operative intervention. Increased weight and decreased age of the patient and a thinner tibial component were significant predictors of an increased risk of failure (p < 0.01). Examination of retrieved tibial components revealed extensive delamination caused by fracture of the polyethylene at a depth of about one millimeter below the surface. Cracks that had propagated in from the medial and lateral peripheries of the tibial component toward the center of the condyles were also a common finding. It appears that the design of the implant as well as clinical factors (the age and weight of the patient) contributed to the mechanical failure of the polyethylene of these implants.