290 research outputs found
Gaining Balance: Toward a Grounded Theory of the Decision-Making Processes of Applicants for Adoption of Children with and without Disabilities
A grounded theory is presented of the decision-making processes among applicants when considering available children with and without disabilities for domestic public adoption. Using grounded theory methodology (Strauss & Corbin, 1998), data from 15 adoption applicants were analyzed followed the traditional three coding phases. The central category of Adoption Decision Making is labeled Gaining Balance and was the underpinning concept to all categories and sub-categories (i.e., in parentheses) of the theory: Commitment (e.g., motivation, financial considerations), Persistence (e.g., coping with emotions, counteracting pessimism), and Evaluation (e.g., assessments of personal abilities and resources, assessments of knowledge of potential adoptees\u27 needs). The results are compared to existing literature and implications for child welfare practices and further research are discussed
Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh a randomized controlled trial
Author version made available in accordance with pubilsher policy. 12 month embargo applies from the date of publication (1 Feb 2015).Objective:
Determine whether absorbable or non-absorbable mesh in repair of large hiatus hernias reduces
the risk of recurrence, compared to suture repair.
Summary Background Data:
Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%,
and to improve outcomes mesh repair has been recommended. Previous trials have shown
less short term recurrence with mesh, but adverse outcomes limit mesh use.
Methods:
Multicentre prospective double blind randomized controlled trial of 3 methods of repair; sutures
vs. absorbable mesh vs. non-absorbable mesh. Primary outcome - hernia recurrence assessed by
barium meal X-ray and endoscopy at 6 months. Secondary outcomes - clinical symptom scores at
1, 3, 6 and 12 months.
Results:
126 patients enrolled - 43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 96.0%
were followed to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any
size) was identified in 23.1% following suture repair, 30.8% - absorbable mesh, and 12.8% -
non-absorbable mesh (p=0.161). Clinical outcomes were similar, except less heartburn at 3 &
6 months and less bloating at 12 months with non-absorbable mesh, and more heartburn at 3
months, odynophagia at 1 month, nausea at 3 & 12 months, wheezing at 6 months, and
inability to belch at 12 months following absorbable mesh. The magnitude of the clinical
differences were small.
Conclusions:
No significant differences were seen for recurrent hiatus hernia, and the clinical differences
were unlikely to be clinically significant. Overall outcomes following sutured repair were
similar to mesh repair
Frailty of MÄori, Pasifika, and non-MÄori/non-Pasifika older people in New Zealand: a national population study of older people referred for home care services
Little is known about the prevalence of frailty in indigenous populations. We developed a frailty index for older New Zealand MÄori and Pasifika who require publicly funded support services.A frailty index (FI) was developed for New Zealand adults aged ā„65 years who had an interRAI-Home Care assessment between 1 June 2012 and 30 October 2015. A frailty score for each participant was calculated by summing the number of deficits recorded and dividing by the total number of possible deficits. This created a FI with a potential range from 0 to 1. Linear regression models for FIs with ethnicity were adjusted for age and sex. Cox proportional hazards models were used to assess the association between the FI and mortality for MÄori, Pasifika, and non-MÄori/non-Pasifika.Of 54,345 participants, 3,096 (5.7%) identified as MÄori, 1,846 (3.4%) were Pasifika, and 49,415 (86.7%) identified as neither MÄori nor Pasifika. New Zealand Europeans (48,178, 97.5%) constituted most of the latter group. Within each sex, the mean FIs for MÄori and Pasifika were greater than the mean FIs for non-MÄori and non-Pasifika, with the difference being more pronounced in females. The FI was associated with mortality (MÄori SHR 2.53, 95% CI 1.63 to 3.95; Pasifika SHR 6.03, 95% CI 3.06 to 11.90; non-MÄori and non-Pasifika SHR 2.86, 95% 2.53 to 3.25).This study demonstrated differences in FI between the ethnicities in this select cohort. After adjustment for age and sex, increases in FI were associated with increased mortality. This suggests that FI is predictive of poor outcomes in these ethnic groups
Global and mitosis-specific interobserver variation in mitotic count scoring and implications for malignant melanoma staging
AIMS
Staging is the gold standard for predicting malignant melanoma outcome but changes in its criteria over time indicate ongoing evolution. One notable recent change from the 8 edition of the AJCC staging manual was removal of mitotic count. We explore the extent that this feature is limited by interobserver error in order to find ways to improve its fitness for use should it be revisited in future staging versions.
METHODS AND RESULTS
In a cohort of 476 patients with melanoma ā¤ 1.0 mm, a mitotic count of 0 vs 1 was significant for metastasis-free survival, but not melanoma-specific or overall survival. In 10 melanomas that were 0.9 to 1.0 mm thick, the mitotic count intra-class correlation coefficient for histopathologists was 0.58 (moderate agreement). Uniquely, we also assessed agreement for specific putative mitotic figures, identifying precise reasons why specific mitotic figures qualified for scoring or elimination. A kappa score was 0.54 (moderate agreement). We also gathered data on other staging features. Breslow thickness had an intraclass correlation coefficient of 0.41 (moderate agreement) and there was a systematic difference between histopathologists across cases (p = 0.04). Every case had a range that crossed the AJCC8 0.8 mm pT1a/pT1b staging boundary. Ulceration was only identified in 2 out the 10 cases. For ulceration, kappa agreement score was 0.31 (fair).
CONCLUSION
This study supports the removal of mitotic count from staging but shows that its scoring is substantially affected by interobserver variation, suggesting that more prescriptive guidelines might have a beneficial impact on its prognostic value
Mechanism of Crosstalk between the LSD1 Demethylase and HDAC1 Deacetylase in the CoREST Complex.
The transcriptional corepressor complex CoREST is one of seven histone deacetylase complexes that regulate the genome through controlling chromatin acetylation. The CoREST complex is unique in containing both histone demethylase and deacetylase enzymes, LSD1 and HDAC1, held together by the RCOR1 scaffold protein. To date, it has been assumed that the enzymes function independently within the complex. Now, we report the assembly of the ternary complex. Using both structural and functional studies, we show that the activity of the two enzymes is closely coupled and that the complex can exist in at least two distinct states with different kinetics. Electron microscopy of the complex reveals a bi-lobed structure with LSD1 and HDAC1 enzymes at opposite ends of the complex. The structure of CoREST in complex with a nucleosome reveals a mode of chromatin engagement that contrasts with previous models
Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer
In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel
A comment on the PCAST report:skip the āmatchā/ānon-matchā stage
This letter comments on the report āForensic science in criminal courts: Ensuring scientific validity of feature-comparison methodsā recently released by the President's Council of Advisors on Science and Technology (PCAST). The report advocates a procedure for evaluation of forensic evidence that is a two-stage procedure in which the first stage is āmatchā/ānon-matchā and the second stage is empirical assessment of sensitivity (correct acceptance) and false alarm (false acceptance) rates. Almost always, quantitative data from feature-comparison methods are continuously-valued and have within-source variability. We explain why a two-stage procedure is not appropriate for this type of data, and recommend use of statistical procedures which are appropriate
Activity pacing: moving beyond taking breaks and slowing down
This brief communication responds to the paper by Jeong and Cho (Qual Life Res 26(4):903ā911, 2017) that has described activity pacing in limited terms of adjusting activities through going at a slower rate and taking breaks. Activity pacing was reported as not involving goal setting, in comparison to other strategies for long-term conditions such as Acceptance and Commitment Therapy. This brief communication aims to challenge this limited perception of activity pacing in light of numerous studies that recognise pacing to be a more complex strategy. Pacing is considered to be a multifaceted coping strategy, including broad themes of not only adjusting activities, but also planning activities, having consistent activity levels, acceptance of current abilities and gradually increasing activities, and one that includes goal setting as a key facet. It is essential that pacing is both defined and measured as a multifaceted strategy in order to assess the outcomes of pacing, and for meaningful comparisons with other strategies regarding efficacy for the management of long-term conditions
Biological Misinterpretation of Transcriptional Signatures in Tumor Samples Can Unknowingly Undermine Mechanistic Understanding and Faithful Alignment with Preclinical Data
PURPOSE
Precise mechanism-based gene expression signatures (GES) have been developed in appropriate in vitro and in vivo model systems, to identify important cancer-related signaling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumor samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumor stroma percentage can directly influence GESs, undermining the intended mechanistic signaling.
EXPERIMENTAL DESIGN
Using colorectal cancer as an exemplar, we deployed numerous orthogonal profiling methodologies, including laser capture microdissection, flow cytometry, bulk and multiregional biopsy clinical samples, single-cell RNA sequencing and finally spatial transcriptomics, to perform a comprehensive assessment of the potential for the most widely used GESs to be influenced, or confounded, by stromal content in tumor tissue. To complement this work, we generated a freely-available resource, ConfoundR; https://confoundr.qub.ac.uk/, that enables users to test the extent of stromal influence on an unlimited number of the genes/signatures simultaneously across colorectal, breast, pancreatic, ovarian and prostate cancer datasets.
RESULTS
Findings presented here demonstrate the clear potential for misinterpretation of the meaning of GESs, due to widespread stromal influences, which in-turn can undermine faithful alignment between clinical samples and preclinical data/models, particularly cell lines and organoids, or tumor models not fully recapitulating the stromal and immune microenvironment.
CONCLUSIONS
Efforts to faithfully align preclinical models of disease using phenotypically-designed GESs must ensure that the signatures themselves remain representative of the same biology when applied to clinical samples
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