Description: Based upon a survey of global auroral images collected by the Polar UVI instrument, [19] subdivided polar cap auroral arcs into a number of categories, including that of ‘bending’ arcs. We are concerned with those bending arcs that appear as a bifurcation of the dayside auroral oval, and which subsequently form a spur intruding into the polar cap. Once formed the spur moves polewards and antisunwards over the lifetime of the arc. We propose that dayside bending arcs are ionospheric signatures of pulses of dayside reconnection, and are therefore part of a group of transient phenomena associated with flux transfer events. We observe the formation and subsequent motion of a bending arc across the polar cap during a 30 minute interval on 8 January 1999, and we show that this example is consistent with the proposed model. We quantify the motion of the arc, and find it to be commensurate with the convection flows observed by both ground-based radar observations and space-based particle flow measurements. In addition, precipitating particles coincident with the arc appear to occur along open field lines, lending further support to the model.

Description: Objectives (1) To explain general practitioners’ (GPs’) approaches to prostate-specific antigen (PSA) testing and overdiagnosis; (2) to explain how GPs reason about their PSA testing routines and (3) to explain how these routines influence GPs’ personal experience as clinicians. Setting Primary care practices in Australia including men's health clinics and rural practices with variable access to urology services. Participants 32 urban and rural GPs within Australia. We included GPs of varying ages, gender (11 female), clinical experience and patient populations. All GPs interested in participating in the study were included. Primary and secondary outcome measure(s) Data were analysed using grounded theory methods to determine how and why GPs provide (or do not provide) PSA testing to their asymptomatic male patients. Results We observed patterned variation in GP practice, and identified four heuristics to describe GP preference for, and approaches to, PSA testing and overdiagnosis: (1) GPs who prioritised avoiding underdiagnosis, (2) GPs who weighed underdiagnosis and overdiagnosis case by case, (3) GPs who prioritised avoiding overdiagnosis and (4) GPs who did not engage with overdiagnosis at all. The heuristics guided GPs’ Routine Practice (usual testing, communication and responses to patient request). The heuristics also reflected GPs’ different Practice Rationales (drawing on experience, medicolegal obligations, guidelines and evidence) and produced different Practice Outcomes (GPs’ experiences of the consequences of their PSA testing decisions). Some of these heuristics were more responsive to patient preferences than others. Conclusions Variation in GPs’ PSA testing practices is strongly related to their approach to overdiagnosis and underdiagnosis of prostate cancer. Men receive very different care depending on their GP's reasoning and practice preferences. Future policy to address overdiagnosis will be more likely to succeed if it responds to these patterned variations.

Description: Digital dermatitis (DD) is an important cause of lameness in dairy cattle worldwide. It has now been reported in beef cattle and also sheep (contagious ovine digital dermatitis [CODD]). Three Treponema phylogroups are consistently isolated from lesions, Treponema medium- like, Treponema phagedenis -like, and Treponema pedis . The gastrointestinal (GI) tract and feces are suggested sites of treponemal infection in dairy cattle; however, isolation of DD-associated treponemes from these areas has previously failed. This study surveyed gingival tissues, rectal tissues, and feces of beef cattle and sheep for the molecular presence (PCR) and isolation of the three cultivable DD-treponeme phylogroups. Of the sheep gingival ( n = 40) and rectal ( n = 40) tissues, 1/40 gingival tissues was positive for DD-associated treponemes ( T. pedis ), as were 3/40 rectal tissues (one containing T. medium- like and two containing T. pedis ). No DD-associated treponeme DNA was amplified from beef cattle rectal tissues ( n = 40); however, 4/40 beef gingival tissues were positive for DD-associated treponemes (all containing T. phagedenis -like). A T. phagedenis -like DD-associated treponeme was isolated from the rectal tissue of a CODD symptomatic sheep. Beef cattle ( n = 41) and sheep ( n = 79) feces failed to amplify DD-associated Treponema DNA. Twenty-two treponemes were isolated from sheep feces; however, upon phylogenetic analysis, these clustered with the considered nonpathogenic treponemes. This study detected DD-associated treponemes in the GI tract tissues of sheep and beef cattle and successfully isolated a DD-associated treponeme from ruminant rectal tissue. This gives evidence that the GI tract is an important infection reservoir of DD-associated treponemes in multiple DD-infected species.

Description: Treponema species are implicated in many diseases of humans and animals. Digital dermatitis (DD) treponemes are reported to cause severe lesions in cattle, sheep, pigs, goats, and wild elk, causing substantial global animal welfare issues and economic losses. The fastidiousness of these spirochetes has previously precluded studies investigating within-phylogroup genetic diversity. An archive of treponemes that we isolated enabled multilocus sequence typing to quantify the diversity and population structure of DD treponemes. Isolates ( n = 121) were obtained from different animal hosts in nine countries on three continents. The analyses herein of currently isolated DD treponemes at seven housekeeping gene loci confirm the classification of the three previously designated phylogroups: the Treponema medium , Treponema phagedenis , and Treponema pedis phylogroups. Sequence analysis of seven DD treponeme housekeeping genes revealed a generally low level of diversity among the strains within each phylogroup, removing the need for the previously used "-like" suffix. Surprisingly, all isolates within each phylogroup clustered together, regardless of host or geographic origin, suggesting that the same sequence types (STs) can infect different animals. Some STs were derived from multiple animals from the same farm, highlighting probable within-farm transmissions. Several STs infected multiple hosts from similar geographic regions, identifying probable frequent between-host transmissions. Interestingly, T. pedis appears to be evolving more quickly than the T. medium or T. phagedenis DD treponeme phylogroup, by forming two unique ST complexes. The lack of phylogenetic discrimination between treponemes isolated from different hosts or geographic regions substantially contrasts with the data for other clinically relevant spirochetes. IMPORTANCE The recent expansion of the host range of digital dermatitis (DD) treponemes from cattle to sheep, goats, pigs, and wild elk, coupled with the high level of 16S rRNA gene sequence similarity across hosts and with human treponemes, suggests that the same bacterial species can cause disease in multiple different hosts. This multilocus sequence typing (MLST) study further demonstrates that these bacteria isolated from different hosts are indeed very similar, raising the potential for cross-species transmission. The study also shows that infection spread occurs frequently, both locally and globally, suggesting transmission by routes other than animal-animal transmission alone. These results indicate that on-farm biosecurity is important for controlling disease spread in domesticated species. Continued surveillance and vigilance are important for ascertaining the evolution and tracking any further host range expansion of these important pathogens.

Description: We report laboratory measurements of the parallel current carried by suprathermal electrons associated with inertial Alfvén wave excitation in the laboratory. The experiments presented here use a novel wave absorption diagnostic that measures the suprathermal tails of the electron distribution parallel to the mean magnetic field. The diagnostic is used to probe the electron distribution as an inertial Alfvén wave propagates along the mean magnetic field. These results identify, for the first time, the periodic motion of suprathermal electrons participating in the inertial Alfvén wave itself, in agreement with predictions from linear kinetic theory.

Description: Too much medicine is an increasingly recognised problem,1 2 and one manifestation is inappropriate polypharmacy in older people. Polypharmacy is usually defined as taking more than five regular...

Description: Objective To elicit informed views from Australian women aged 70–74 regarding the acceptability of ceasing to invite women their age to participate in government-funded mammography screening (BreastScreen). Design Two community juries held in 2017. Setting Greater Sydney, a metropolis of 4.5 million people in New South Wales, Australia. Participants 34 women aged 70–74 with no personal history of breast cancer, recruited by random digit dialling and previously randomly recruited list-based samples. Main outcomes and measures Jury verdict and rationale in response to structured questions. We transcribed audio-recorded jury proceedings and identified central reasons for the jury’s decision. Results The women’s average age was 71.5 years. Participants were of diverse sociocultural backgrounds, with the sample designed to include women of lower levels of educational attainment. Both juries concluded by majority verdict (16–2 and 10–6) that BreastScreen should continue to send invitations and promote screening to their age group. Reasons given for the majority position include: (1) sending the invitations shows that society still cares about older women, empowers them to access preventive health services and recognises increasing and varied life expectancy; (2) screening provides women with information that enables choice and (3) if experts cannot agree, the conservative approach is to maintain the status quo until the evidence is clear. Reasons for the minority position were the potential for harms through overdiagnosis and misallocation of scarce health resources. Conclusions Preventive programmes such as mammography screening are likely to have significant symbolic value once they are socially embedded. Arguments for programme de-implementation emphasising declining benefit because of limited life expectancy and the risks of overdiagnosis seem unlikely to resonate with healthy older women. In situations where there is no consensus among experts on the value of established screening programmes, people may strongly prefer receiving information about their health and having the opportunity make their own choices.

Description: Purpose: Squamous cell carcinoma of the anal canal (ASCC) accounts for 2% to 4% of gastrointestinal malignancies in the United States and is increasing in incidence; however, genomic features of ASCC are incompletely characterized. Primary treatment of ASCC involves concurrent chemotherapy and radiation (CRT), but the mutational landscape of resistance to CRT is unknown. Here, we aim to compare mutational features of ASCC in the pre- and post-CRT setting. Experimental Design: We perform whole-exome sequencing of primary ( n = 31) and recurrent ( n = 30) ASCCs and correlate findings with clinical data. We compare genomic features of matched pre- and post-CRT tumors to identify genomic features of CRT response. Finally, we investigate the mutational underpinnings of an extraordinary ASCC response to immunotherapy. Results: We find that both primary and recurrent ASCC tumors harbor mutations in genes, such as PIK3CA and FBXW7 , that are also mutated in other HPV-associated cancers. Overall mutational burden was not significantly different in pre- versus post-CRT tumors, and several examples of shared clonal driver mutations were identified. In two cases, clonally related pre- and post-CRT tumors harbored distinct oncogenic driver mutations in the same cancer gene ( KRAS or FBXW7 ). A patient with recurrent disease achieved an exceptional response to anti-programmed death (PD-1) therapy, and genomic dissection revealed high mutational burden and predicted neoantigen load. Conclusions: We perform comprehensive mutational analysis of ASCC and characterize mutational features associated with CRT. Although many primary and recurrent tumors share driver events, we identify several unique examples of clonal evolution in response to treatment. Clin Cancer Res; 23(12); 3214–22. ©2016 AACR .

Description: Two co-existing transpolar arcs are observed on the 31st August 2005. We track the formation and motion of the arcs in both the Northern and Southern Hemisphere, using data from two independent satellites (Imager for Magnetopause to Aurora Global Exploration and a Defence Meteorological Satellite Program satellite). The observations are supported by supplementary ground-based ionospheric convection data from the Super Dual Auroral Radar Network. The two arcs form during a period of northward interplanetary magnetic field. Following a change in the direction of the IMF B Y component from negative to positive, the dawn side arc traverses the polar cap to the dusk side in the Northern Hemisphere. Over the same time period and in the Southern Hemisphere, the dusk side arc traverses the polar cap to the dawn side. A complex magnetic field line topology resulting in the coexistence of two tongues of closed field lines protruding into the otherwise open polar cap is implied. We discuss these observations in terms of magnetic conjugacy and a model of TPA formation.

Description: Transgenic mouse models expressing mutant superoxide dismutase 1 ( SOD1 ) have been critical in furthering our understanding of amyotrophic lateral sclerosis (ALS). However, such models generally overexpress the mutant protein, which may give rise to phenotypes not directly relevant to the disorder. Here, we have analysed a novel mouse model that has a point mutation in the endogenous mouse Sod1 gene; this mutation is identical to a pathological change in human familial ALS (fALS) which results in a D83G change in SOD1 protein. Homozgous Sod1 D83G/D83G mice develop progressive degeneration of lower (LMN) and upper motor neurons, likely due to the same unknown toxic gain of function as occurs in human fALS cases, but intriguingly LMN cell death appears to stop in early adulthood and the mice do not become paralyzed. The D83 residue coordinates zinc binding, and the D83G mutation results in loss of dismutase activity and SOD1 protein instability. As a result, Sod1 D83G/D83G mice also phenocopy the distal axonopathy and hepatocellular carcinoma found in Sod1 null mice ( Sod1 –/– ). These unique mice allow us to further our understanding of ALS by separating the central motor neuron body degeneration and the peripheral effects from a fALS mutation expressed at endogenous levels.