This inaugural volume in the Graphic Medicine series establishes the principles of graphic medicine and begins to map the field. The volume combines scholarly essays by members of the editorial team ...with previously unpublished visual narratives by Ian Williams and MK Czerwiec, and it includes arresting visual work from a wide range of graphic medicine practitioners. The book’s first section, featuring essays by Scott Smith and Susan Squier, argues that as a new area of scholarship, research on graphic medicine has the potential to challenge the conventional boundaries of academic disciplines, raise questions about their foundations, and reinvigorate literary scholarship—and the notion of the literary text—for a broader audience. The second section, incorporating essays by Michael Green and Kimberly Myers, demonstrates that graphic medicine narratives can engage members of the health professions with literary and visual representations and symbolic practices that offer patients, family members, physicians, and other caregivers new ways to experience and work with the complex challenges of the medical experience. The final section, by Ian Williams and MK Czerwiec, focuses on the practice of creating graphic narratives, iconography, drawing as a social practice, and the nature of comics as visual rhetoric. A conclusion (in comics form) testifies to the diverse and growing graphic medicine community. Two valuable bibliographies guide readers to comics and scholarly works relevant to the field.
The saturated fatty acids acylated on Lipid A of lipopolysaccharide (LPS) or bacterial lipoproteins play critical roles in ligand recognition and receptor activation for Toll-like Receptor 4 (TLR4) ...and TLR2. The results from our previous studies demonstrated that saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4. However, the underlying mechanism has not been understood. Here, we report for the first time that the saturated fatty acid lauric acid induced dimerization and recruitment of TLR4 into lipid rafts, however, dimerization was not observed in non-lipid raft fractions. Similarly, LPS and lauric acid enhanced the association of TLR4 with MD-2 and downstream adaptor molecules, TRIF and MyD88, into lipid rafts leading to the activation of downstream signaling pathways and target gene expression. However, docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, inhibited LPS- or lauric acid-induced dimerization and recruitment of TLR4 into lipid raft fractions. Together, these results demonstrate that lauric acid and DHA reciprocally modulate TLR4 activation by regulation of the dimerization and recruitment of TLR4 into lipid rafts. In addition, we showed that TLR4 recruitment to lipid rafts and dimerization were coupled events mediated at least in part by NADPH oxidase-dependent reactive oxygen species generation. These results provide a new insight in understanding the mechanism by which fatty acids differentially modulate TLR4-mediated signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases.
Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association ...studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this ...trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.
In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.
Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 35% patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 35% patients) in the placebo group (hazard ratio 0·23 95% CI 0·16–0·34; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 63% vs 118 62%), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 0·24–0·42; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 0·30–0·45; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 99% patients in the rucaparib group vs 189 100% in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 19% vs one 1%) and increased alanine or aspartate aminotransferase concentration (39 10% vs none).
Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.
Clovis Oncology.
Mechanotransduction is the physiological process where cells sense and respond to mechanical loads. This paper reclaims the term "mechanotherapy" and presents the current scientific knowledge ...underpinning how load may be used therapeutically to stimulate tissue repair and remodelling in tendon, muscle, cartilage and bone. The purpose of this short article is to answer a frequently asked question "How precisely does exercise promote tissue healing?" This is a fundamental question for clinicians who prescribe exercise for tendinopathies, muscle tears, non-inflammatory arthropathies and even controlled loading after fractures. High-quality randomised controlled trials and systematic reviews show that various forms of exercise or movement prescription benefit patients with a wide range of musculoskeletal problems.1(-)4 But what happens at the tissue level to promote repair and remodelling of tendon, muscle, articular cartilage and bone? The one-word answer is "mechanotransduction", but rather than finishing there and limiting this paper to 95 words, we provide a short illustrated introduction to this remarkable, ubiquitous, non-neural, physiological process. We also re-introduce the term "mechanotherapy" to distinguish therapeutics (exercise prescription specifically to treat injuries) from the homeostatic role of mechanotransduction. Strictly speaking, mechanotransduction maintains normal musculoskeletal structures in the absence of injury. After first outlining the process of mechanotransduction, we provide well-known clinical therapeutic examples of mechanotherapy-turning movement into tissue healing.
APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 105 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV ...(SDSS-IV). APOGEE-2 is expanding on APOGEE's goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.
Breslau J, Miller E, Jin R, Sampson NA, Alonso J, Andrade LH, Bromet EJ, de Girolamo G, Demyttenaere K, Fayyad J, Fukao A, Gălăon M, Gureje O, He Y, Hinkov HR, Hu C, Kovess‐Masfety V, Matschinger H, ...Medina‐Mora ME, Ormel J, Posada‐Villa J, Sagar R, Scott KM, Kessler RC. A multinational study of mental disorders, marriage, and divorce.
Objective: Estimate predictive associations of mental disorders with marriage and divorce in a cross‐national sample.
Method: Population surveys of mental disorders included assessment of age at first marriage in 19 countries (n = 46 128) and age at first divorce in a subset of 12 countries (n = 30 729). Associations between mental disorders and subsequent marriage and divorce were estimated in discrete time survival models.
Results: Fourteen of 18 premarital mental disorders are associated with lower likelihood of ever marrying (odds ratios ranging from 0.6 to 0.9), but these associations vary across ages of marriage. Associations between premarital mental disorders and marriage are generally null for early marriage (age 17 or younger), but negative associations come to predominate at later ages. All 18 mental disorders are positively associated with divorce (odds ratios ranging from 1.2 to 1.8). Three disorders, specific phobia, major depression, and alcohol abuse, are associated with the largest population attributable risk proportions for both marriage and divorce.
Conclusion: This evidence adds to research demonstrating adverse effects of mental disorders on life course altering events across a diverse range of socioeconomic and cultural settings. These effects should be included in considerations of public health investments in preventing and treating mental disorders.
The Drug Design Data Resource aims to test and advance the state of the art in protein–ligand modeling by holding community-wide blinded, prediction challenges. Here, we report on our third major ...round, Grand Challenge 3 (GC3). Held 2017–2018, GC3 centered on the protein Cathepsin S and the kinases VEGFR2, JAK2, p38-α, TIE2, and ABL1, and included both pose-prediction and affinity-ranking components. GC3 was structured much like the prior challenges GC2015 and GC2. First, Stage 1 tested pose prediction and affinity ranking methods; then all available crystal structures were released, and Stage 2 tested only affinity rankings, now in the context of the available structures. Unique to GC3 was the addition of a Stage 1b self-docking subchallenge, in which the protein coordinates from all of the cocrystal structures used in the cross-docking challenge were released, and participants were asked to predict the pose of CatS ligands using these newly released structures. We provide an overview of the outcomes and discuss insights into trends and best-practices.
Treatment of suicidal people around the world Bruffaerts, Ronny; Demyttenaere, Koen; Hwang, Irving ...
British journal of psychiatry,
07/2011, Letnik:
199, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Suicide is a leading cause of death worldwide; however, little information is available about the treatment of suicidal people, or about barriers to treatment.
To examine the receipt of mental health ...treatment and barriers to care among suicidal people around the world.
Twenty-one nationally representative samples worldwide (n=55 302; age 18 years and over) from the World Health Organization's World Mental Health Surveys were interviewed regarding past-year suicidal behaviour and past-year healthcare use. Suicidal respondents who had not used services in the past year were asked why they had not sought care.
Two-fifths of the suicidal respondents had received treatment (from 17% in low-income countries to 56% in high-income countries), mostly from a general medical practitioner (22%), psychiatrist (15%) or non-psychiatrist (15%). Those who had actually attempted suicide were more likely to receive care. Low perceived need was the most important reason for not seeking help (58%), followed by attitudinal barriers such as the wish to handle the problem alone (40%) and structural barriers such as financial concerns (15%). Only 7% of respondents endorsed stigma as a reason for not seeking treatment.
Most people with suicide ideation, plans and attempts receive no treatment. This is a consistent and pervasive finding, especially in low-income countries. Improving the receipt of treatment worldwide will have to take into account culture-specific factors that may influence the process of help-seeking.
ABSTRACT
We present Gemini-S and Spitzer-IRAC optical-through-near-IR observations in the field of the SPT2349-56 proto-cluster at z = 4.3. We detect optical/IR counterparts for only 9 of the 14 ...submillimetre galaxies (SMGs) previously identified by ALMA in the core of SPT2349-56. In addition, we detect four z ∼ 4 Lyman-break galaxies (LBGs) in the 30 arcsec-diameter region surrounding this proto-cluster core. Three of the four LBGs are new systems, while one appears to be a counterpart of one of the nine observed SMGs. We identify a candidate brightest cluster galaxy (BCG) with a stellar mass of $(3.2^{+2.3}_{-1.4})\times 10^{11}$ M⊙. The stellar masses of the eight other SMGs place them on, above, and below the main sequence of star formation at z ≈ 4.5. The cumulative stellar mass for the SPT2349-56 core is at least (12.2 ± 2.8) × 1011 M⊙, a sizeable fraction of the stellar mass in local BCGs, and close to the universal baryon fraction (0.19) relative to the virial mass of the core (1013 M⊙). As all 14 of these SMGs are destined to quickly merge, we conclude that the proto-cluster core has already developed a significant stellar mass at this early stage, comparable to z = 1 BCGs. Importantly, we also find that the SPT2349-56 core structure would be difficult to uncover in optical surveys, with none of the ALMA sources being easily identifiable or constrained through g, r, and i colour selection in deep optical surveys and only a modest overdensity of LBGs over the more extended structure. SPT2349-56 therefore represents a truly dust-obscured phase of a massive cluster core under formation.
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