Networks and social capital: a relational approach to primary healthcare reform

Collaboration among health care providers and across systems is proposed as a strategy to improve health care delivery the world over. Over the past two decades, health care providers have been encouraged to work in partnership and build interdisciplinary teams. More recently, the notion of networks has entered this discourse but the lack of consensus and understanding about what is meant by adopting a network approach in health services limits its use. Also crucial to this discussion is the work of distinguishing the nature and extent of the impact of social relationships – generally referred to as social capital. In this paper, we review the rationale for collaboration in health care systems; provide an overview and synthesis of key concepts; dispel some common misconceptions of networks; and apply the theory to an example of primary healthcare network reform in Alberta (Canada). Our central thesis is that a relational approach to systems change, one based on a synthesis of network theory and social capital can provide the fodation for a multi-focal approach to primary healthcare reform. Action strategies are recommended to move from an awareness of 'networks' to fully translating knowledge from existing theory to guide planning and practice innovations. Decision-makers are encouraged to consider a multi-focal approach that effectively incorporates a network and social capital approach in planning and evaluating primary healthcare reform

Structural Comparison of Human Mammalian Ste20-Like Kinases

BACKGROUND: The serine/threonine mammalian Ste-20 like kinases (MSTs) are key regulators of apoptosis, cellular proliferation as well as polarization. Deregulation of MSTs has been associated with disease progression in prostate and colorectal cancer. The four human MSTs are regulated differently by C-terminal regions flanking the catalytic domains. PRINCIPAL FINDINGS: We have determined the crystal structure of kinase domain of MST4 in complex with an ATP-mimetic inhibitor. This is the first structure of an inactive conformation of a member of the MST kinase family. Comparison with active structures of MST3 and MST1 revealed a dimeric association of MST4 suggesting an activation loop exchanged mechanism of MST4 auto-activation. Together with a homology model of MST2 we provide a comparative analysis of the kinase domains for all four members of the human MST family. SIGNIFICANCE: The comparative analysis identified new structural features in the MST ATP binding pocket and has also defined the mechanism for autophosphorylation. Both structural features may be further explored for inhibitors design. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S1

Comorbid mental disorders in substance users from a single catchment area - a clinical study

<p>Abstract</p> <p>Background</p> <p>The optimal treatment of patients with substance use disorders (SUDs) requires an awareness of their comorbid mental disorders and vice versa. The prevalence of comorbidity in first-time-admitted SUD patients has been insufficiently studied. Diagnosing comorbidity in substance users is complicated by symptom overlap, symptom fluctuations, and the limitations of the assessment methods. The aim of this study was to diagnose all mental disorders in substance users living in a single catchment area, without any history of treatment for addiction or psychiatric disorders, admitted consecutively to the specialist health services. The prevalence of substance-induced versus substance-independent disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), in SUD patients will be described.</p> <p>Methods</p> <p>First-time consecutively admitted patients from a single catchment area, aged 16 years or older, admitted to addiction clinics or departments of psychiatry as outpatients or inpatients will be screened for substance-related problems using the Alcohol Use Disorder Identification Test and the Drug Use Disorder Identification Test. All patients with scores above the cutoff value will be asked to participate in the study. The patients included will be diagnosed for SUD and other axis I disorders by a psychiatrist using the Psychiatric Research Interview for Substance and Mental Disorders. This interview was designed for the diagnosis of primary and substance-induced disorders in substance users. Personality disorders will be assessed according to the Structured Clinical Interview for DSM-IV axis II disorders. The Symptom Checklist-90-Revised, the Inventory of Depressive Symptoms, the Montgomery Asberg Depression Rating Scale, the Young Mania Rating Scale, and the Angst Hypomania Check List will be used for additional diagnostic assessments. The sociodemographic data will be recorded with the Stanley Foundation's Network Entry Questionnaire. Biochemical assessments will reveal somatic diseases that may contribute to the patient's symptoms.</p> <p>Discussion</p> <p>This study is unique because the material represents a complete sample of first-time-admitted treatment seekers with SUD from a single catchment area. Earlier studies have not focused on first-time-admitted patients, so chronically ill patients, may have been overrepresented in those samples. This study will contribute new knowledge about mental disorders in first-time-admitted SUD patients.</p

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Islamic influences on urban form in Sumatra in the seventeenth to nineteenth centuries CE

This article focuses on the evolution of three urban centres: Palembang, Padang and Tanjung Pinang. Where appropriate, brief information about other towns is added which shows that the three towns are typical for towns on the east coast, the west coast and the islands in the Straits of Malacca respectively. Unfortunately, there is no place in the Minangkabau highlands for which historical sources exist that can help to reconstruct the townscape in a comparably detailed way. The descriptions of Palembang, Padang and Tanjung Pinang give details of Islamic buildings and provide information about the development of the settlements as a whole. These morphological histories have a value in their own right. They form a baseline to assess fully the specific Islamic influence on urban form in the disruption of some Islamic transformations. The Dutch changes bring out the previous Islamic influences more sharply. In the last section the emic (indigenous) conceptions of 'urban' will be analysed, by exploring the contrast between town and village and the role of Islamic buildings to accentuate the difference. The conclusion will list the most important empirical generalisations drawn from the descriptions. © 2004 Editors, Indonesia and the Malay World

Bilateral motor unit synchronization is functionally organized.

To elucidate the neural interactions underlying bimanual coordination, we investigated in 11 participants the bilateral coupling of homologous muscles in an isometric force production task involving fatiguing elbow flexion and extension. We focused on changes in motor unit (MU) synchronization as evident in EMG recordings of relevant muscles. In contrast to a related study on leg muscles, the arm muscles did not exhibit MU synchronization around 16 Hz, consistent with our hypothesis that 16 Hz MU synchronization is linked to balance maintenance. As expected, bilateral MU synchronization was apparent between 8 and 12 Hz and increased with fatigue and more strongly so for extensor than for flexor muscles. MU synchronization in that frequency band is interpreted in terms of common bilateral input and substantiates the idea that common input is functionally organized. Since these findings are consistent with the literature on mirror movements, they suggest that both phenomena may be related. © 2006 Springer-Verlag