CONTEXT Although chest pain is widely considered a key symptom in the diagnosis
of myocardial infarction (MI), not all patients with MI present with chest
pain. The extent to which this phenomenon ...occurs is largely unknown. OBJECTIVES To determine the frequency with which patients with MI present without
chest pain and to examine their subsequent management and outcome. DESIGN Prospective observational study. SETTING AND PATIENTS A total of 434,877 patients with confirmed MI enrolled June 1994 to
March 1998 in the National Registry of Myocardial Infarction 2, which includes
1674 hospitals in the United States. MAIN OUTCOME MEASURES Prevalence of presentation without chest pain; clinical characteristics,
treatment, and mortality among MI patients without chest pain vs those with
chest pain. RESULTS Of all patients diagnosed as having MI, 142,445 (33%) did not have chest
pain on presentation to the hospital. This group of MI patients was, on average,
7 years older than those with chest pain (74.2 vs 66.9 years), with a higher
proportion of women (49.0% vs 38.0%) and patients with diabetes mellitus (32.6%
vs 25.4%) or prior heart failure (26.4% vs 12.3%). Also, MI patients without
chest pain had a longer delay before hospital presentation (mean, 7.9 vs 5.3
hours), were less likely to be diagnosed as having confirmed MI at the time
of admission (22.2% vs 50.3%), and were less likely to receive thrombolysis
or primary angioplasty (25.3% vs 74.0%), aspirin (60.4% vs 84.5%), β-blockers
(28.0% vs 48.0%), or heparin (53.4% vs 83.2%). Myocardial infarction patients
without chest pain had a 23.3% in-hospital mortality rate compared with 9.3%
among patients with chest pain (adjusted odds ratio for mortality, 2.21 95%
confidence interval, 2.17-2.26). CONCLUSIONS Our results suggest that patients without chest pain on presentation
represent a large segment of the MI population and are at increased risk for
delays in seeking medical attention, less aggressive treatments, and in-hospital
mortality.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a loss of immunologic tolerance to a multitude of self-antigens. Epidemiological data suggest an important role for genes ...in the etiology of lupus, and previous genetic studies have implicated the HLA locus, complement genes, and low-affinity IgG (Fcγ) receptors in SLE pathogenesis. In an effort to identify new susceptibility loci for SLE, we recently reported the results of a genomewide microsatellite marker screen in 105 SLE sib-pair families. By using nonparametric methods, evidence for linkage was found in four intervals: 6p11-21 (near the HLA), 16q13, 14q21-23, and 20p12.3 (LOD scores ⩾2.0), and weaker evidence in another nine regions. We now report the results of a second complete genome screen in a new cohort of 82 SLE sib-pair families. In the cohort 2 screen, the four best intervals were 7p22 (LOD score 2.87), 7q21 (LOD score 2.40), 10p13 (LOD score 2.24), and 7q36 (LOD score 2.15). Eight additional intervals were identified with LOD scores in the range 1.00–1.67. A combined analysis of MN cohorts 1 and 2 (187 sib-pair families) showed that markers in 6p11-p21 (D6S426, LOD score 4.19) and 16q13 (D16S415, LOD score 3.85) met the criteria for significant linkage. Three intervals (2p15, 7q36, and 1q42) had LOD scores in the range 1.92–2.06, and another 13 intervals had LOD scores in the range of 1.00–1.78 in the combined sample. These data, together with other available gene mapping results in SLE, are beginning to allow a prioritization of genomic intervals for gene discovery efforts in human SLE.
Systemic lupus erythematosus (SLE) is an autoimmune multisystem inflammatory disease characterized by the production of pathogenic autoantibodies. Previous genetic studies have suggested associations ...with HLA Class II alleles, complement gene deficiencies, and Fc receptor polymorphisms; however, it is likely that other genes contribute to SLE susceptibility and pathogenesis. Here, we report the results of a genome-wide microsatellite marker screen in 105 SLE sib-pair families. By using multipoint nonparametric methods, the strongest evidence for linkage was found near the HLA locus (6p11-p21) D6S257, logarithm of odds (lod) = 3.90, P = 0.000011 and at three additional regions: 16q13 (D16S415, lod = 3.64, P = 0.000022), 14q21-23 (D14S276, lod = 2.81, P = 0.00016), and 20p12 (D20S186, lod = 2.62, P = 0.00025). Another nine regions (1p36, 1p13, 1q42, 2p15, 2q21-33, 3cent-q11, 4q28, 11p15, qne 15q26) were identified with lod scores ≥ 1.00. These data support the hypothesis that multiple genes, including one in the HLA region, influence susceptibility to human SLE.
Traumatic injuries to the primary dentition present special problems and the management is often different as compared with the permanent dentition. The International Association of Dental ...Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialities were included in the task group. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion or majority decision of the task group. Finally, the IADT board members were giving their opinion and approval. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care for management of primary teeth injuries. The IADT cannot and does not guarantee favorable outcomes from strict adherence to the guidelines, but believe that their application can maximize the chances of a positive outcome.
– Avulsion of permanent teeth is one of the most serious dental injuries, and a prompt and correct emergency management is very important for the prognosis. The International Association of Dental ...Traumatology (IADT) has developed a consensus statement after a review of the dental literature and group discussions. Experienced researchers and clinicians from various specialties were included in the task group. The guidelines represent the current best evidence and practice based on literature research and professionals’ opinion. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion or majority decision of the task group. Finally, the IADT board members were giving their opinion and approval. The primary goal of these guidelines is to delineate an approach for the immediate or urgent care of avulsed permanent teeth.
Despite the high heritability of autism spectrum disorders (ASD), characterized by persistent deficits in social communication and interaction and restricted, repetitive patterns of behavior, ...interests or activities, a genetic diagnosis can be established in only a minority of patients. Known genetic causes include chromosomal aberrations, such as the duplication of the 15q11-13 region, and monogenic causes, as in Rett and fragile-X syndromes. The genetic heterogeneity within ASD is striking, with even the most frequent causes responsible for only 1% of cases at the most. Even with the recent developments in next-generation sequencing, for the large majority of cases no molecular diagnosis can be established. Here, we report ten patients with ASD and other shared clinical characteristics, including intellectual disability and facial dysmorphisms caused by a mutation in ADNP, a transcription factor involved in the SWI/SNF remodeling complex. We estimate this gene to be mutated in at least 0.17% of ASD cases, making it one of the most frequent ASD-associated genes known to date.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Standardized, research-based strategies to guide the implementation and evaluate the effects of housing adaptations (HA) on client outcomes are rare. We hypothesized that, compared to ordinary ...practice, a standardized assessment and evaluation protocol for HA implementation would better maintain or improve client outcomes over 1 year.
Using a cluster design, South Swedish municipalities were recruited to an intervention or control group. Data on activities of daily living, usability of the home, health related quality of life, and participation frequency and satisfaction were collected at home visits 1 month before the HA (baseline; T1), and at 3 (T2), 6 (T3) and 12 (T4) months after. In the intervention group (n = 112) data were collected according to a standardized protocol while in the control group (n = 129) ordinary routines were applied. Changes from baseline to subsequent time points were categorized as no deterioration (i.e. improvement or no change) or deterioration, for each outcome item separately. Differences in "no deterioration" between the groups were assessed using logistic regression.
Little effect of using the standardized protocol was detected. For activities of daily living, statistically significant differences between the groups were found for toileting (T1-T4; OR 3.14), dressing (T1-T4; OR2.89) and cooking (T1-T3 and T1-T4; OR 3.14). For usability of the home differences were found in personal hygiene (T1-T2; OR 2.32) using a wheelchair (T1-T2 and T1-T3; OR 9.50), picking up the mail (T1-T3; OR 4.06), and in participation, helping others (T1-T3 and T1-T4; OR 2.33 and 3.36).
The applied standardized protocol for HA implementation did not show any convincing effect, possibly due to the complexity of the intervention itself, and the implementation process. A process evaluation might generate in-depth knowledge about the reasons behind the findings.
ClinicalTrials.gov . NCT01960582.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Wheat, one of the most important food crops, is threatened by a blast disease pandemic. Here, we show that a clonal lineage of the wheat blast fungus recently spread to Asia and Africa following two ...independent introductions from South America. Through a combination of genome analyses and laboratory experiments, we show that the decade-old blast pandemic lineage can be controlled by the Rmg8 disease resistance gene and is sensitive to strobilurin fungicides. However, we also highlight the potential of the pandemic clone to evolve fungicide-insensitive variants and sexually recombine with African lineages. This underscores the urgent need for genomic surveillance to track and mitigate the spread of wheat blast outside of South America and to guide preemptive wheat breeding for blast resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome ...sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test.
We analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n = 68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n = 156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure.
First, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850 kb (min 500 bp, max 155 Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (> 10 kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data. Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively.
The overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.
Public trust is central to the collection of genomic and health data and the sustainability of genomic research. To merit trust, those involved in collecting and sharing data need to demonstrate they ...are trustworthy. However, it is unclear what measures are most likely to demonstrate this.
We analyse the 'Your DNA, Your Say' online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle- and high-income countries, gathered in 15 languages. We examine how participants perceived the relative value of measures to demonstrate the trustworthiness of those using donated DNA and/or medical information. We examine between-country variation and present a consolidated ranking of measures.
Providing transparent information about who will benefit from data access was the most important measure to increase trust, endorsed by more than 50% of participants across 20 of 22 countries. It was followed by the option to withdraw data and transparency about who is using data and why. Variation was found for the importance of measures, notably information about sanctions for misuse of data-endorsed by 5% in India but almost 60% in Japan. A clustering analysis suggests alignment between some countries in the assessment of specific measures, such as the UK and Canada, Spain and Mexico and Portugal and Brazil. China and Russia are less closely aligned with other countries in terms of the value of the measures presented.
Our findings highlight the importance of transparency about data use and about the goals and potential benefits associated with data sharing, including to whom such benefits accrue. They show that members of the public value knowing what benefits accrue from the use of data. The study highlights the importance of locally sensitive measures to increase trust as genomic data sharing continues globally.
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