Neisseria gonorrhoeae false-positive result obtained from a pharyngeal swab by using the roche cobas 4800 CT/NG assay in New Zealand in 2012

The Roche cobas 4800 CT/NG assay is a commonly used commercial system for screening for Neisseria gonorrhoeae infection, and previous studies have shown the method to be highly sensitive and specific for urogenital samples. We present the first confirmed clinical N. gonorrhoeae false-positive result using the cobas 4800 NG assay, obtained from testing a pharyngeal swab sample and caused by cross-reaction with a commensal Neisseria strain

Human papillomavirus (HPV) self-sampling among never- and under-screened indigenous Māori, Pacific and Asian women in Aotearoa New Zealand: A Feasibility Study

In Aotearoa New Zealand the majority of cervical cancer cases occur in women who have never been screened or are under-screened. Wāhine Māori, Pacific and Asian women have the lowest rate of cervical screening. Self-sampling for human papillomavirus (HPV-SS) has been shown to increase participation in cervical-cancer screening. A whole-of-system approach, driven by evidence in the most effective delivery of HPV-SS, is required to mitigate further widening of the avoidable gap in cervical screening access and outcomes between groups of women in Aotearoa. This single-arm feasibility and acceptability study of HPV self-sampling invited never- and under-screened (≥5 years overdue) 30-69-year-old women from general practices in Auckland, Aotearoa. Eligible women were identified by data matching between the National Cervical Programme (NCSP) Register and practice data. Focus groups were additionally held with eligible wāhine Māori, Asian and Pacific women to co-design new patient information materials. Questionnaires on HPV knowledge and post-test experience were offered to women. Our follow-up protocols included shared decision-making principles and we committed to follow-up ≥90% of women who tested positive for HPV. Data matching identified 366 eligible never- and under-screened wāhine Māori, Pacific and Asian women in participating practices. We were only able to contact 114 women and 17 on discussion were found to be ineligible. Identifying and contacting women overdue for a cervical screen was resource intensive, with a high rate of un-contactability despite multiple attempts. We found the best uptake of self-sampling was at focus groups. Of the total 84 HPV-SS tests, there were 5 positive results (6%), including 1 participant with HPV18 who was found to have a cervical adenocarcinoma at colposcopy. In our feasibility study, self-sampling was acceptable and effective at detecting HPV and preventing cervical cancer in under-screened urban wāhine Māori, Pacific and Asian women in Aotearoa. This is the first report of a cervical adenocarcinoma (Grade 1B) as a result of an HPV-18 positive self-sample in Aotearoa. We co-designed new patient information materials taking a health literacy and ethnicity-specific approach. This work provides policy relevant information to the NCSP on the resources required to implement an effective HPV self-sampling programme to improve equity in national cervical cancer screening

Comparison of the cobas 4800 CT/NG test with culture for detecting neisseria gonorrhoeae in genital and nongenital specimens in a low-prevalence population in New Zealand

To assess the clinical utility of replacing microbial culture for Neisseria gonorrhoeae with a nucleic acid amplification test (NAAT), we compared N. gonorrhoeae culture with the cobas 4800 CT/NG test for 18,247 urogenital and 666 nongenital samples. For urogenital specimens, the sensitivity, specificity, and positive and negative predictive values of the cobas N. gonorrhoeae PCR were 98.7%, 100%, 95.6%, and 100%, respectively, and for nongenital specimens, the values were 100%, 99.8%, 92.9%, and 100%, respectively. In our test population, 37% (10,185) of patients tested over the study period were screened for C. trachomatis by PCR but were not screened for gonorrhea by culture. Of these, 43 were N. gonorrhoeae positive by PCR and therefore went undiagnosed. The cobas 4800 CT/NG test diagnosed 33% (n=30) more urogenital and 25% (n=3) more rectal gonorrhea infections than culture and, based on the above performance indicators, does not require supplementary testing for urogenital or rectal specimens. The ability to test noninvasive specimens (such as urine and self-taken vulvovaginal swabs) for N. gonorrhoeae will enable more patients to be screened for infection, thus offering significant positive public health benefits. Copyrigh

Mutations in RAB39B Cause X-Linked Intellectual Disability and Early-Onset Parkinson Disease with alpha-Synuclein Pathology

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a approximately 45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of alpha-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of alpha-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of alpha-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders

Trade blocs and trade wars during the interwar period

What precisely were the causes and consequences of the trade wars in the 1930s? Were there perhaps deeper forces at work in reorienting global trade prior to the outbreak of World War II? And what lessons may this particular historical episode provide for the present day? To answer these questions, we distinguish between long‐run secular trends in the period from 1920 to 1939 related to the formation of trade blocs and short‐run disruptions associated with the trade wars of the 1930s. We argue that the trade wars mainly served to intensify pre‐existing efforts toward the formation of trade blocs which dated from at least 1920. More speculatively, we argue that the trade wars of the present day may serve a similar purpose as those in the 1930s, that is, the intensification of China‐ and US‐centric trade blocs

Where Snow is a Landmark: Route Direction Elements in Alpine Contexts

Route directions research has mostly focused on urban space so far, highlighting human concepts of street networks based on a range of recurring elements such as route segments, decision points, landmarks and actions. We explored the way route directions reflect the features of space and activity in the context of mountaineering. Alpine route directions are only rarely segmented through decision points related to reorientation; instead, segmentation is based on changing topography. Segments are described with various degrees of detail, depending on difficulty. For landmark description, direction givers refer to properties such as type of surface, dimension, colour of landscape features; terrain properties (such as snow) can also serve as landmarks. Action descriptions reflect the geometrical conceptualization of landscape features and dimensionality of space. Further, they are very rich in the semantics of manner of motion

Investigating Behaviour and Population Dynamics of Striped Marlin (Kajikia audax) from the Southwest Pacific Ocean with Satellite Tags

Behaviour and distribution of striped marlin within the southwest Pacific Ocean were investigated using electronic tagging data collected from 2005–2008. A continuous-time correlated random-walk Kalman filter was used to integrate double-tagging data exhibiting variable error structures into movement trajectories composed of regular time-steps. This state-space trajectory integration approach improved longitude and latitude error distributions by 38.5 km and 22.2 km respectively. Using these trajectories as inputs, a behavioural classification model was developed to infer when, and where, ‘transiting’ and ‘area-restricted’ (ARB) pseudo-behavioural states occurred. ARB tended to occur at shallower depths (108±49 m) than did transiting behaviours (127±57 m). A 16 day post-release period of diminished ARB activity suggests that patterns of behaviour were affected by the capture and/or tagging events, implying that tagged animals may exhibit atypical behaviour upon release. The striped marlin in this study dove deeper and spent greater time at ≥200 m depth than those in the central and eastern Pacific Ocean. As marlin reached tropical latitudes (20–21°S) they consistently reversed directions, increased swimming speed and shifted to transiting behaviour. Reversals in the tropics also coincided with increases in swimming depth, including increased time ≥250 m. Our research provides enhanced understanding of the behavioural ecology of striped marlin. This has implications for the effectiveness of spatially explicit population models and we demonstrate the need to consider geographic variation when standardizing CPUE by depth, and provide data to inform natural and recreational fishing mortality parameters

New, simplified and improved interpretation of the Vaiont landslide mechanics

Both the occurrence and behaviour of the Vaiont landslide have not been satisfactorily explained previously because of difficulties arising from the assumption that the failure surface was ‘chair’ shaped. It is now known that there was no ‘chair’, which means that the 1963 landslide could not have been a reactivated ancient landslide because the residual strength of the clay interbeds would have been insufficient for stability prior to 1963. Furthermore, the moderately translational geometry reduces the influence of reservoir-induced groundwater and hence of submergence. Standard stability analyses now show that prior to 1960, the average shear strength must have significantly exceeded the peak shear strength of the clay interbeds known to have formed the majority of the failure surface. Three-dimensional stability analyses confirm these results and show that at the time of the first significant movements in 1960, the rising reservoir level had a negligible effect on the Factor of Safety. According to these results, the Vaiont landslide was most likely initiated by pore water pressures associated with transient rainfall-induced ‘perched’ groundwater above the clay layers, in combination with a smaller than hitherto assumed effect of reservoir impounding, then developed by brittle crack propagation within the clay beds, thus displaying progressive failure. Further, very heavy rainfall accelerated the process, possibly due to reservoir-induced groundwater impeding drainage of the rainwater, until the limestone beds at the northeast margin failed. With the shear strength suddenly reduced to residual throughout, the entire mass was released and was able to accelerate as observed