Characterizing the role of disparity information in alleviating visual crowding

The ability to identify a target is reduced by the presence of nearby objects, a phenomenon known as visual crowding. The extent to which crowding impairs our perception is generally governed by the degree of similarity between a target stimulus and its surrounding flankers. Here we investigated the influence of disparity differences between target and flankers on crowding. Orientation discrimination thresholds for a parafoveal target were first measured when the target and flankers were presented at the same depth to establish a flanker separation that induced a significant elevation in threshold for each individual. Flankers were subsequently fixed at this spatial separation while the disparity of the flankers relative to the target was altered. For all participants, thresholds showed a systematic decrease as flanker-target disparity increased. The resulting tuning function was asymmetric: Crowding was lower when the target was perceived to be in front of the flankers rather than behind. A series of control experiments confirmed that these effects were driven by disparity, as opposed to other factors such as flanker-target separation in three-dimensional (3-D) space or monocular positional offsets used to create disparity. When flankers were distributed over a range of crossed and uncrossed disparities, such that the mean was in the plane of the target, there was an equivalent or greater release of crowding compared to when all flankers were presented at the maximum disparity of that range. Overall, our results suggest that depth cues can reduce the effects of visual crowding, and that this reduction is unlikely to be caused by grouping of flankers or positional shifts in the monocular image

Identification of people with autosomal dominant polycystic kidney disease using routine data: a cross sectional study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) causes progressive renal damage and is a leading cause of end-stage renal failure. With emerging therapies it is important to devise a method for early detection. We aimed to identify factors from routine clinical data which can be used to distinguish people with a high likelihood of having ADPKD in a primary health care setting. METHOD: A cross-sectional study was undertaken using data from the Quality Intervention in Chronic Kidney Disease trial extracted from 127 primary care practices in England. The health records of 255 people with ADPKD were compared to the general population. Logistic regression was used to identify clinical features which distinguish ADPKD. These clinical features were used to stratify individual risk using a risk score tool. RESULTS: Renal impairment, proteinuria, haematuria, a diastolic blood pressure over 90 mmHg and multiple antihypertensive medications were more common in ADPKD than the general population and were used to build a regression model (area under the receiver operating characteristic curve; 0.79). Age, gender, haemoglobin and urinary tract infections were not associated with ADPKD. A risk score (range -3 to +10) of ≥0 gave a sensitivity of 70.2% and specificity 74.9% of for detection. CONCLUSIONS: Stratification of ADPKD likelihood from routine data may be possible. This approach could be a valuable component of future screening programs although further longitudinal analyses are needed

The Impact of Depression on Patient Outcomes in Hip Arthroscopic Surgery.

Background: Mental health impairments have been shown to negatively affect preoperative self-reported function in patients with various musculoskeletal disorders, including those with femoroacetabular impingement. Hypothesis: Those with symptoms of depression will have lower self-reported function, more pain, and less satisfaction on initial assessment and at 2-year follow-up than those without symptoms of depression. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who were enrolled in a multicenter hip arthroscopic surgery registry and had 2-year outcome data available were included in the study. Patients completed the 12-item International Hip Outcome Tool (iHOT-12), visual analog scale (VAS) for pain, and 12-item Short-Form Health Survey (SF-12) when consenting for surgery. At 2-year follow-up, patients were emailed the iHOT, the VAS, and a rating scale of surgical satisfaction. Initial SF-12 mental component summary (MCS) scores Results: A total of 781 patients achieved the approximate 2-year milestone (mean follow-up, 735 ± 68 days), with 651 (83%) having 2-year outcome data available. There were 434 (67%) female and 217 (33%) male patients, with a mean age of 35.8 ± 13.0 years and a mean body mass index of 25.4 ± 8.8 kg/m Conclusion: A large number of patients who underwent hip arthroscopic surgery presented with symptoms of depression, which negatively affected self-reported function, pain levels, and satisfaction on initial assessment and at 2-year follow-up. Surgeons who perform hip arthroscopic surgery may need to identify the symptoms of depression and be aware of the impact that depression can have on surgical outcomes

Time trends in prescribing of type 2 diabetes drugs, glycaemic response and risk factors:a retrospective analysis of primary care data, 2010-2017

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordAim: Prescribing in type 2 diabetes has changed markedly in recent years, with increasing use of newer, more expensive glucose-lowering drugs. We aimed to describe population-level time trends in both prescribing patterns and short-term patient outcomes (HbA1c, weight, blood pressure, hypoglycemia and treatment discontinuation) after initiating new therapy. Materials and methods: We studied 81,532 UK patients with type 2 diabetes initiating a first to fourth line drug in primary care between 2010-2017 inclusive (Clinical Practice Research Datalink). Trends in new prescriptions and subsequent six and twelve-month adjusted changes in glycemic response (reduction in HbA1c), weight, blood pressure, and rates of hypoglycemia and treatment discontinuation were examined. Results: DPP4-inhibitor use second-line near doubled (41% of new prescriptions in 2017 vs. 22% 2010), replacing sulfonylureas as the most common second-line drug (29% 2017 vs. 53% 2010). SGLT2-inhibitors, introduced in 2013, comprised 17% of new first-fourth line prescriptions by 2017. First-line use of metformin remained stable (91% of new prescriptions in 2017 vs. 91% 2010). Over the study period there was little change in average glycemic response and treatment discontinuation. There was a modest reduction in weight second and third-line (second line 2017 vs. 2010: -1.5 kg (95%CI -1.9;-1.1), p<0.001), and a slight reduction in systolic blood pressure first to third-line (2017 vs. 2010 difference range -1.7 to -2.1 mmHg, all p<0.001). Hypoglycemia rates decreased second-line (incidence rate ratio 0.94 per-year (95%CI 0.88;1.00, p=0.04)), mirroring the decline in use of sulfonylureas. 4 Conclusions: Recent changes in prescribing of therapy in type 2 diabetes have not led to a change in glycemic response and have resulted in modest improvements in other population-level short-term patient outcomes.Medical Research Council (MRC)National Institute for Health Research (NIHR)Wellcome Trus

Bioarchaeological and Climatological Evidence for the Fate of Norse Farmers in Medieval Greenland

Greenland, far north land of the Atlantic, has often been beyond the limit of European farming settlement. One of its Norse settlements, colonized just before AD 1000, is — astonishingly — not even at the southern tip, but a way up the west coast, the \u27Western Settlement\u27. Environmental studies show why its occupation came to an end within five centuries, leaving Greenland once more a place of Arctic-adapted hunters

Task-specific transfer of perceptual learning across sensory modalities

It is now widely accepted that primary cortical areas of the brain that were once thought to be sensory-specific undergo significant functional reorganisation following sensory deprivation. For instance, loss of vision or audition leads to the brain areas normally associated with these senses being recruited by the remaining sensory modalities [1]. Despite this, little is known about the rules governing crossmodal plasticity in people who experience typical sensory development, or the potential behavioural consequences. Here, we used a novel perceptual learning paradigm to assess whether the benefits associated with training on a task in one sense transfer to another sense. Participants were randomly assigned to a spatial or temporal task that could be performed visually or aurally, which they practiced for five days; before and after training, we measured discrimination thresholds on all four conditions and calculated the extent of transfer between them. Our results show a clear transfer of learning between sensory modalities; however, generalisation was limited to particular conditions. Specifically, learned improvements on the spatial task transferred from the visual domain to the auditory domain, but not vice versa. Conversely, benefits derived from training on the temporal task transferred from the auditory domain to visual domain, but not vice versa. These results suggest a unidirectional transfer of perceptual learning from dominant to non-dominant sensory modalities and place important constraints on models of multisensory processing and plasticity

Development of a treatment selection algorithm for SGLT2 and DPP-4 inhibitor therapies in people with type 2 diabetes:a retrospective cohort study

Background: Current treatment guidelines do not provide recommendations to support the selection of treatment for most people with type 2 diabetes. We aimed to develop and validate an algorithm to allow selection of optimal treatment based on glycaemic response, weight change, and tolerability outcomes when choosing between SGLT2 inhibitor or DPP-4 inhibitor therapies. Methods: In this retrospective cohort study, we identified patients initiating SGLT2 and DPP-4 inhibitor therapies after Jan 1, 2013, from the UK Clinical Practice Research Datalink (CPRD). We excluded those who received SGLT2 or DPP-4 inhibitors as first-line treatment or insulin at the same time, had estimated glomerular filtration rate (eGFR) of less than 45 mL/min per 1·73 m2, or did not have a valid baseline glycated haemoglobin (HbA1c) measure (&lt;53 or ≥120 mmol/mol). The primary efficacy outcome was the HbA1c value reached 6 months after drug initiation, adjusted for baseline HbA1c. Clinical features associated with differential HbA1c outcome on the two therapies were identified in CPRD (n=26 877), and replicated in reanalysis of 14 clinical trials (n=10 414). An algorithm to predict individual-level differential HbA1c outcome on the two therapies was developed in CPRD (derivation; n=14 069) and validated in head-to-head trials (n=2499) and CPRD (independent validation; n=9376). In CPRD, we further explored heterogeneity in 6-month weight change and treatment discontinuation. Findings: Among 10 253 patients initiating SGLT2 inhibitors and 16 624 patients initiating DPP-4 inhibitors in CPRD, baseline HbA1c, age, BMI, eGFR, and alanine aminotransferase were associated with differential HbA1c outcome with SGLT2 inhibitor and DPP-4 inhibitor therapies. The median age of participants was 62·0 years (IQR 55·0–70·0). 10 016 (37·3%) were women and 16 861 (62·7%) were men. An algorithm based on these five features identified a subgroup, representing around four in ten CPRD patients, with a 5 mmol/mol or greater observed benefit with SGLT2 inhibitors in all validation cohorts (CPRD 8·8 mmol/mol [95% CI 7·8–9·8]; CANTATA-D and CANTATA-D2 trials 5·8 mmol/mol [3·9–7·7]; BI1245.20 trial 6·6 mmol/mol [2·2–11·0]). In CPRD, predicted differential HbA1c response with SGLT2 inhibitor and DPP-4 inhibitor therapies was not associated with weight change. Overall treatment discontinuation within 6 months was similar in patients predicted to have an HbA1c benefit with SGLT2 inhibitors over DPP-4 inhibitors (median 15·2% [13·2–20·3] vs 14·4% [12·9–16·7]). A smaller subgroup predicted to have greater HbA1c reduction with DPP-4 inhibitors were twice as likely to discontinue SGLT2 inhibitors than DPP-4 inhibitors (median 26·8% [23·4–31·0] vs 14·8% [12·9–16·8]). Interpretation: A validated treatment selection algorithm for SGLT2 inhibitor and DPP-4 inhibitor therapies can support decisions on optimal treatment for people with type 2 diabetes. Funding: BHF-Turing Cardiovascular Data Science Award and the UK Medical Research Council

Prescribing in type 2 diabetes patients with and without cardiovascular disease history: A descriptive analysis in the UK CPRD

PURPOSE: Some classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). METHODS: Four cross-sections of people with T2DM aged 18-90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. FINDINGS: Around 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9-9.1%) and 8.9% (8.6-9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0-19.5%) and 21.2% (20.6-21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0-24.4%) and 25.9% (25.2-26.6%) in January 2017 to 41.3% (39.5-43.0%) and 45.5% (44.7-46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. IMPLICATIONS: Although use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit

First isolation of Brucella pinnipedialis and detection of Brucella antibodies from bearded seals Erignathus barbartus

Brucella species infecting marine mammals was first reported in 1994 and in the years since has been documented in various species of pinnipeds and cetaceans. While these reports have included species that inhabit Arctic waters, the few available studies on bearded seals Erignathus barbatus have failed to detect Brucella infection to date. We report the first isolation of Brucella pinnipedialis from a bearded seal. The isolate was recovered from the mesenteric lymph node of a bearded seal that stranded in Scotland and typed as ST24, a sequence type associated typically with pinnipeds. Furthermore, serological studies of free-ranging bearded seals in their native waters detected antibodies to Brucella in seals from the Chukchi Sea (1990-2011; 19%) and Svalbard (1995-2007; 8%), whereas no antibodies were detected in bearded seals from the Bering Sea or Bering Strait or from captive bearded seals

Treatment effect heterogeneity following type 2 diabetes treatment with GLP1-receptor agonists and SGLT2-inhibitors:a systematic review

Background: A precision medicine approach in type 2 diabetes requires the identification of clinical and biological features that are reproducibly associated with differences in clinical outcomes with specific anti-hyperglycaemic therapies. Robust evidence of such treatment effect heterogeneity could support more individualized clinical decisions on optimal type 2 diabetes therapy.Methods: We performed a pre-registered systematic review of meta-analysis studies, randomized control trials, and observational studies evaluating clinical and biological features associated with heterogenous treatment effects for SGLT2-inhibitor and GLP1-receptor agonist therapies, considering glycaemic, cardiovascular, and renal outcomes. After screening 5,686 studies, we included 101 studies of SGLT2-inhibitors and 75 studies of GLP1-receptor agonists in the final systematic review.Results: Here we show that the majority of included papers have methodological limitations precluding robust assessment of treatment effect heterogeneity. For SGLT2-inhibitors, multiple observational studies suggest lower renal function as a predictor of lesser glycaemic response, while markers of reduced insulin secretion predict lesser glycaemic response with GLP1-receptor agonists. For both therapies, multiple post-hoc analyses of randomized control trials (including trial meta-analysis) identify minimal clinically relevant treatment effect heterogeneity for cardiovascular and renal outcomes.Conclusions: Current evidence on treatment effect heterogeneity for SGLT2-inhibitor and GLP1-receptor agonist therapies is limited, likely reflecting the methodological limitations of published studies. Robust and appropriately powered studies are required to understand type 2 diabetes treatment effect heterogeneity and evaluate the potential for precision medicine to inform future clinical care.</p