Misdiagnosis, Mistreatment, and Harm - When Medical Care Ignores Social Forces.

The Case Studies in Social Medicine demonstrate that when physicians use only biologic or individual behavioral interventions to treat diseases that stem from or are exacerbated by social factors, we risk harming the patients we seek to serve

Reliability and Validity of S3 Pressure Sensation as an Alternative to Deep Anal Pressure in Neurologic Classification of Persons With Spinal Cord Injury.

OBJECTIVE: To determine whether pressure sensation at the S3 dermatome (a new test) could be used in place of deep anal pressure (DAP) to determine completeness of injury as part of the International Standards for Neurological Classification of Spinal Cord Injury. DESIGN: Prospective, multicenter observational study. SETTING: U.S. Spinal Cord Injury Model Systems. PARTICIPANTS: Persons (N=125) with acute traumatic spinal cord injury (SCI), neurologic levels T12 and above, were serially examined at 1 month (baseline), 3, 6, and 12 months postinjury. There were 80 subjects with tetraplegia and 45 with paraplegia. INTERVENTIONS: S3 pressure sensation at all time points, with a retest at the 1-month time point. MAIN OUTCOME MEASURES: Test-retest reliability and agreement (κ), sensitivity, specificity, positive and negative predictive values. RESULTS: Test-retest reliability of S3 pressure at 1 month was almost perfect (κ=.98). Agreement of S3 pressure with DAP was substantial both at 1 month (κ=.73) and for all time points combined (κ=.76). The positive predictive value of S3 pressure for DAP was 89.3% at baseline and 90.3% for all time points. No pattern in outcomes was seen in those cases where S3 pressure and DAP differed at 1 month. CONCLUSIONS: S3 pressure sensation is reliable and has substantial agreement with DAP in persons with SCI at least 1 month postinjury. We suggest S3 pressure as an alternative test of sensory sacral sparing for supraconus SCI, at least in cases where DAP cannot be tested. Further research is needed to determine whether S3 pressure could replace DAP for classification of SCI

Scattering by coupled resonating elements in air

Scattering by (a) a single composite scatterer consisting of a concentric arrangement of an outer N-slit rigid cylinder and an inner cylinder which is either rigid or in the form of a thin elastic shell and (b) by a finite periodic array of these scatterers in air has been investigated analytically and through laboratory experiments. The composite scatterer forms a system of coupled resonators and gives rise to multiple low-frequency resonances. The corresponding analytical model employs polar angle dependent boundary conditions on the surface of the N-slit cylinder. The solution inside the slits assumes plane waves. It is shown also that in the low-frequency range the N-slit rigid cylinder can be replaced by an equivalent fluid layer. Further approximations suggest a simple square root dependence of the resonant frequencies on the number of slits and this is confirmed by data. The observed resonant phenomena are associated with Helmholtz-like behaviour of the resonator for which the radius and width of the openings are much smaller than the wavelength. The problem of scattering by a finite periodic array of such coupled resonators in air is solved using multiple scattering techniques. The resulting model predicts band-gap effects resulting from the resonances of the individual composite scatterers below the first Bragg frequency. Predictions and data confirm that use of coupled resonators results in substantial insertion loss peaks related to the resonances within the concentric configuration. In addition, for both scattering problems experimental data, predictions of the analytical approach and predictions of the equivalent fluid layer approximations are compared in the low-frequency interval

Instability in clinical risk stratification models using deep learning

While it has been well known in the ML community that deep learning models suffer from instability, the consequences for healthcare deployments are under characterised. We study the stability of different model architectures trained on electronic health records, using a set of outpatient prediction tasks as a case study. We show that repeated training runs of the same deep learning model on the same training data can result in significantly different outcomes at a patient level even though global performance metrics remain stable. We propose two stability metrics for measuring the effect of randomness of model training, as well as mitigation strategies for improving model stability.Comment: Accepted for publication in Machine Learning for Health (ML4H) 202

Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation.

The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 Å using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation

We are all one together : peer educators\u27 views about falls prevention education for community-dwelling older adults - a qualitative study

Background: Falls are common in older people. Despite strong evidence for effective falls prevention strategies, there appears to be limited translation of these strategies from research to clinical practice. Use of peers in delivering falls prevention education messages has been proposed to improve uptake of falls prevention strategies and facilitate translation to practice. Volunteer peer educators often deliver educational presentations on falls prevention to community-dwelling older adults. However, research evaluating the effectiveness of peer-led education approaches in falls prevention has been limited and no known study has evaluated such a program from the perspective of peer educators involved in delivering the message. The purpose of this study was to explore peer educators’ perspective about their role in delivering peer-led falls prevention education for community-dwelling older adults. Methods: A two-stage qualitative inductive constant comparative design was used.In stage one (core component) focus group interviews involving a total of eleven participants were conducted. During stage two (supplementary component) semi-structured interviews with two participants were conducted. Data were analysed thematically by two researchers independently. Key themes were identified and findings were displayed in a conceptual framework. Results: Peer educators were motivated to deliver educational presentations and importantly, to reach an optimal peer connection with their audience. Key themes identified included both personal and organisational factors that impact on educators’ capacity to facilitate their peers’ engagement with the message. Personal factors that facilitated message delivery and engagement included peer-to-peer connection and perceived credibility, while barriers included a reluctance to accept the message that they were at risk of falling by some members in the audience. Organisational factors, including ongoing training for peer educators and formative feedback following presentations, were perceived as essential because they affect successful message delivery. Conclusions: Peer educators have the potential to effectively deliver falls prevention education to older adults and influence acceptance of the message as they possess the peer-to-peer connection that facilitates optimal engagement. There is a need to consider incorporating learnings from this research into a formal large scale evaluation of the effectiveness of the peer education approach in reducing falls in older adults

Structure of a putative NTP pyrophosphohydrolase: YP_001813558.1 from Exiguobacterium sibiricum 255-15.

The crystal structure of a putative NTPase, YP_001813558.1 from Exiguobacterium sibiricum 255-15 (PF09934, DUF2166) was determined to 1.78 Å resolution. YP_001813558.1 and its homologs (dimeric dUTPases, MazG proteins and HisE-encoded phosphoribosyl ATP pyrophosphohydrolases) form a superfamily of all-α-helical NTP pyrophosphatases. In dimeric dUTPase-like proteins, a central four-helix bundle forms the active site. However, in YP_001813558.1, an unexpected intertwined swapping of two of the helices that compose the conserved helix bundle results in a `linked dimer' that has not previously been observed for this family. Interestingly, despite this novel mode of dimerization, the metal-binding site for divalent cations, such as magnesium, that are essential for NTPase activity is still conserved. Furthermore, the active-site residues that are involved in sugar binding of the NTPs are also conserved when compared with other α-helical NTPases, but those that recognize the nucleotide bases are not conserved, suggesting a different substrate specificity

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Structure of an essential bacterial protein YeaZ (TM0874) from Thermotoga maritima at 2.5 Å resolution

The crystal structure of an essential bacterial protein, YeaZ, from T. maritima identifies an interface that potentially mediates protein–protein interaction