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BackgroundMeasuring free-living gait using wearable devices may offer higher granularity and temporal resolution than the current clinical assessments for patients with Parkinson disease (PD). However, increasing the number of devices worn on the body adds to the patient burden and impacts the compliance. ObjectiveThis study aimed to investigate the impact of reducing the number of wearable devices on the ability to assess gait impairments in patients with PD. MethodsA total of 35 volunteers with PD and 60 healthy volunteers performed a gait task during 2 clinic visits. Participants with PD were assessed in the On and Off medication state using the Movement Disorder Society version of the Unified Parkinson Disease Rating Scale (MDS-UPDRS). Gait features derived from a single lumbar-mounted accelerometer were compared with those derived using 3 and 6 wearable devices for both participants with PD and healthy participants. ResultsA comparable performance was observed for predicting the MDS-UPDRS gait score using longitudinal mixed-effects model fit with gait features derived from a single (root mean square error [RMSE]=0.64; R2=0.53), 3 (RMSE=0.64; R2=0.54), and 6 devices (RMSE=0.54; R2=0.65). In addition, MDS-UPDRS gait scores predicted using all 3 models differed significantly between On and Off motor states (single device, P=.004; 3 devices, P=.004; 6 devices, P=.045). ConclusionsWe observed a marginal benefit in using multiple devices for assessing gait impairments in patients with PD when compared with gait features derived using a single lumbar-mounted accelerometer. The wearability burden associated with the use of multiple devices may offset gains in accuracy for monitoring gait under free-living conditions.

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

Recent technological advances have expanded the annotated protein coding content of mammalian genomes, as hundreds of previously unidentified, short open reading frame (ORF)-encoded peptides (SEPs) have now been found to be translated. Although several studies have identified important physiological roles for this emerging protein class, a general method to define their interactomes is lacking. Here, we demonstrate that genetic incorporation of the photo-crosslinking noncanonical amino acid AbK into SEP transgenes allows for the facile identification of SEP cellular interaction partners using affinity-based methods. From a survey of seven SEPs, we report the discovery of short ORF-encoded histone binding protein (SEHBP), a conserved microprotein that interacts with chromatin-associated proteins, localizes to discrete genomic loci, and induces a robust transcriptional program when overexpressed in human cells. This work affords a straightforward method to help define the physiological roles of SEPs and demonstrates its utility by identifying SEHBP as a short ORF-encoded transcription factor.

The number of Arctic glaciers with direct, long-term measurements of mass balance is limited. Here we used satellite-based observations of the glacier snowline altitude (SLA), the location of the transition between snow cover and ice late in the summer, to approximate the position of the equilibrium-line altitude (ELA), a variable important for mass balance assessment and for understanding the response of glaciers to climate change. We mapped the snowline (SL) on a subset of 269 land-terminating glaciers above 60° N latitude in the latest available summer, clear-sky Landsat satellite image between 1984 and 2022. The mean SLA was extracted using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM). We compared the remotely observed SLA observations with available long-term field-based measurements of ELA and with ERA5-Land reanalysis climate data. Over the last 4 decades, Arctic glacier SLAs have risen an average of ∼152 m (3.9±0.4 m yr -1 ; R2=0.74 , p<0.001), with a corresponding summer (June, July, August) temperature shift of +1.2 °C at the glacier locations. This equates to a 127±5 m shift per 1 °C of summer warming. However, we note that the effect of glacier surface thinning could bias our estimates of SLA rise by up to ∼1 m yr -1 , a significant fraction (∼25 %) of the overall rate of change, and thus should be interpreted as a maximum constraint. Along with warming, we observe an overall decrease in snowfall, an increase in rainfall, and a decrease in the total number of days in which the mean daily temperature is less than or equal to 0 °C. Glacier SLA is most strongly correlated with the number of freezing days, emphasizing the dual effect of multi-decadal trends in mean annual temperature on both ablation (increasing melt) and accumulation processes (reducing the number of days in which snow can fall). Although we find evidence for a negative morpho-topographic feedback that occurs as glaciers retreat to higher elevations, we show that more than 50 % of the glaciers studied here could be entirely below the late-summer SLA by 2100, assuming the pace of global warming and the mean rate of SLA rise are maintained. [ABSTRACT FROM AUTHOR]

Global hydroclimate significantly differed from modern climate during the mid-Holocene (6 ka) and Last Glacial Maximum (21 ka). Consequently, both periods have been described as either a partial or reverse analogue for current climate change. To reconstruct past hydroclimate, an offline paleoclimate data assimilation methodology is applied to a dataset of 130 lake status records which provide relative estimates of water level measured using percentile units. The proxy observations are integrated with the climate dynamics of two transient simulations (TraCE-21ka and HadCM3) using a multivariate proxy system model (PSM) which estimates relative lake status from available climate simulation variables. The resulting DAMP-21ka (Data Assimilation of Moisture Patterns 21,000–0 BP) reanalysis reconstructs annual lake status and precipitation values at 500-year resolution and represents the first application of the methodology to global hydroclimate on timescales spanning the Holocene and longer. Validation using Pearson's correlation coefficients indicates that the reconstruction (0.33) is more skillful, on average, than model simulations (0.10), particularly in portions of North America and East Africa where data density is high and proxy-model disagreement is prominent during the Holocene. Results of the PSM and assimilation are used to evaluate climatic controls on lake status, spatiotemporal patterns of moisture variability, and proxy-model disagreement. During the mid-Holocene, wetter conditions are reconstructed for North and East Africa, Asia, and southern Australia, but, in contrast to the model prior, negative anomalies are observed in North America resulting in drier than modern conditions throughout the Northern Hemisphere midlatitudes. Proxy-model disagreement in western North America may reflect a bias in model simulations to stronger sea level pressure gradients in the North Pacific during the mid-Holocene. The data assimilation framework is able to reconcile these differences by integrating the constraints of proxy observations with the dynamics of the model prior to produce a more robust estimation of hydroclimate variability during the past 21,000 years. [ABSTRACT FROM AUTHOR]

The number of Arctic glaciers with direct, long–term measurements of mass balance is limited. Here we used satellite–based observations of the glacier snowline altitude (SLA), the location of the transition between snow cover and ice late in the summer, to approximate the position of the equilibrium line altitude (ELA)–a parameter important for mass balance assessment and for understanding the response of glaciers to climate change. We mapped the snowline (SL) on a subset of 269 land–terminating glaciers above 60 °N latitude in the latest available summer, clear–sky Landsat satellite image between 1984 and 2022. The mean SLA was extracted using the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) Global Digital Elevation Model (GDEM). We compare remotely–observed SLA observations with available long–term field–based measurements of ELA and with ERA5–Land reanalysis climate data. Over the last four decades, Arctic glacier SLAs have risen an average of ~152 m (3.9±0.4 m yr–1; R2=0.74, p<0.001), with a corresponding summer (June, July, August) temperature shift of +1.2 °C at the glacier locations. This equates to a 127±5 m shift per 1 °C of summer warming. However, along with warming, we observe an overall decrease in snowfall, an increase in rainfall, and a decrease in the total number of days in which the mean daily temperature is less than or equal to 0 °C. Glacier SLA is most strongly correlated with the number of freezing days, emphasizing the dual effect of multi–decadal trends in mean annual temperature on both ablation (increasing melt) and accumulation processes (reducing the number of days in which snow can fall). Although we find evidence for a negative morpho–topographic feedback that occurs as glaciers retreat to higher elevations, we show that more than 50 % of the glaciers studied here could be entirely below the SLA by 2100, assuming the pace of global warming and the mean rate of SLA rise is maintained. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection. Methods: 28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second‐level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores. Results: Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores. Significance: The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores. Plain language summary: This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left‐sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery. [ABSTRACT FROM AUTHOR]

The latitudinal temperature gradient between the Equator and the poles influences atmospheric stability, the strength of the jet stream and extratropical cyclones.sup.1-3. Recent global warming is weakening the annual surface gradient in the Northern Hemisphere by preferentially warming the high latitudes.sup.4; however, the implications of these changes for mid-latitude climate remain uncertain.sup.5,6. Here we show that a weaker latitudinal temperature gradient--that is, warming of the Arctic with respect to the Equator--during the early to middle part of the Holocene coincided with substantial decreases in mid-latitude net precipitation (precipitation minus evapotranspiration, at 30° N to 50° N). We quantify the evolution of the gradient and of mid-latitude moisture both in a new compilation of Holocene palaeoclimate records spanning from 10° S to 90° N and in an ensemble of mid-Holocene climate model simulations. The observed pattern is consistent with the hypothesis that a weaker temperature gradient led to weaker mid-latitude westerly flow, weaker cyclones and decreased net terrestrial mid-latitude precipitation. Currently, the northern high latitudes are warming at rates nearly double the global average.sup.4, decreasing the Equator-to-pole temperature gradient to values comparable with those in the early to middle Holocene. If the patterns observed during the Holocene hold for current anthropogenically forced warming, the weaker latitudinal temperature gradient will lead to considerable reductions in mid-latitude water resources. A reduced gradient in temperatures between low and high latitudes during the Holocene led to drier mid-latitudes., Author(s): Cody C. Routson [sup.1] , Nicholas P. McKay [sup.1] , Darrell S. Kaufman [sup.1] , Michael P. Erb [sup.1] , Hugues Goosse [sup.2] , Bryan N. Shuman [sup.3] , [...]

Purpose: The success of reverse total shoulder arthroplasty (RTSA) has expanded its use for a broader range of shoulder indications worldwide. Evidence regarding the relative efficacy and long-term safety of medical technologies used in RTSA is subjected to rigorous assessment. Nonetheless, substantial challenges impede market access for innovative shoulder implant technologies for RTSA in Australia, resulting in delayed patient access. Approach: This paper addresses the key challenges associated with generating evidence for the health technology assessments of innovative medical technologies for RTSA that are required for access to the Australian market. The transition to value-based care requires establishing a benchmarking reference that incorporates patient-reported outcome measures (PROMs) and combines revision outcomes with additional clinical outcomes to increase patient cohort sizes. Establishing the benchmark would require agreement on the outcome measures to be collected for each indication, and investment in reporting patient-reported outcomes for RTSA to the national orthopaedic registry. Implications for practice: The need for increased flexibility in developing evidence for health technology assessment of RTSA medical technologies is required. Optimised approaches for benchmarking RTSA require extensive stakeholder discussions, including the agreement on evidence requirements and follow-up periods, selection of clinical outcomes, as well as preoperative and post-operative PROMs as a value assessment. [ABSTRACT FROM AUTHOR]