Long-Term Effects of an Invasive Shore Crab on Cape Cod, Massachusetts

Invasive species can cause dramatic changes in the structure of intertidal communities. In some systems, however, abundance or impacts of invaders may peak 10–20 years after invasion and decline thereafter. Hemigrapsus sanguineus (Asian Shore Crab) has been established at Sandwich, MA, on the north side of Cape Cod, since the mid-1990s. This study documented population dynamics of the Asian Shore Crab and 3 species of prey or competitors (Carcinus maenas [Green Crab], Mytilus edulis [Blue Mussel], and Littorina littorea [Common Periwinkle]) over 10 years. An additional goal of the study was to determine whether population growth of the Asian Shore Crab has slowed since its initial establishment. Density of the Asian Shore Crab increased over time, with no evidence of a density-dependent decrease in per capita growth rates. Concurrently, density of the Green Crab and the Blue Mussel declined, but there was no significant temporal trend in density of the Common Periwinkle. If observations at Sandwich are representative of sites north of Cape Cod, populations of the Asian Shore Crab are growing rapidly, and dramatic changes in community structure may be widespread

Achieving Integration in Mixed Methods Designs—Principles and Practices

Mixed methods research offers powerful tools for investigating complex processes and systems in health and health care. This article describes integration principles and practices at three levels in mixed methods research and provides illustrative examples. Integration at the study design level occurs through three basic mixed method designs—exploratory sequential, explanatory sequential, and convergent—and through four advanced frameworks—multistage, intervention, case study, and participatory. Integration at the methods level occurs through four approaches. In connecting, one database links to the other through sampling. With building, one database informs the data collection approach of the other. When merging, the two databases are brought together for analysis. With embedding, data collection and analysis link at multiple points. Integration at the interpretation and reporting level occurs through narrative, data transformation, and joint display. The fit of integration describes the extent the qualitative and quantitative findings cohere. Understanding these principles and practices of integration can help health services researchers leverage the strengths of mixed methods.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/101791/1/hesr12117.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/101791/2/hesr12117-sup-0001-AuthorMatrix.pd

Do Patients Taking Warfarin Experience Delays to Theatre, Longer Hospital Stay, and Poorer Survival After Hip Fracture?

BACKGROUND: Patients sustaining a fractured neck of the femur are typically of advanced age with multiple comorbidities. As a consequence, the proportion of these patients receiving warfarin therapy is approximately 10%. There are currently few studies investigating outcomes in this subset of patients. QUESTIONS/PURPOSES: The purpose of this study was to assess the association between warfarin therapy and time to surgery, length of hospital stay, and survival in patients sustaining a fractured neck of the femur. METHODS: Data for 2036 patients admitted to our center between July 2009 and July 2014 with a fractured neck of the femur were extracted from the National Hip Fracture Database. Fifty-seven patients received no surgical treatment and were excluded from analysis. Multivariable ordinary least squares regression was performed to test the association between warfarin treatment on time to surgery and length of stay, and Cox proportional hazards to test followup survival. Variables included in the regression model were age, sex, American Society of Anesthesiologists (ASA) score, admission Abbreviated Mental Test Score (AMTS), fracture type, operation type, and premorbid Work Ability Index (WAI). One hundred fifty-two of 1979 surgically treated patients (8%) were receiving warfarin therapy at the time of admission. RESULTS: After controlling for age, sex, ASA score, AMTS, fracture type, operation type, and WAI, we found that patients taking warfarin were less likely to go to surgery by 36 hours (odds ratio [OR], 0.20; 95% CI, 0.14-0.30), and less likely to go to surgery by 48 hours (OR, 0.17; 95% CI, 0.11-0.24). Patients taking warfarin had a longer length of stay (median, 15 days; interquartile range [IQR], 12-22 days) compared with patients not taking warfarin (median, 13 days; IQR, 9-20 days; p < 0.001). Survival analysis to June 2015 showed a higher mortality for patients taking warfarin (12-month survival, 66% vs 76%; hazard ratio, 1.57; 95% CI, 1.21-2.04; p < 0.001). CONCLUSIONS: After controlling for multiple prognostic factors such as age, ASA score, AMTS, and WAI, warfarin therapy at the time of injury is associated with increased time to surgery, length of stay, and decreased survival. This study highlights the need to view warfarin therapy as a 'red flag' in patients presenting with a fractured neck of the femur. Preoperatively, prompt warfarin reversal together with adequate investigation and optimization of the patient should ensure timely, safe surgery. Early involvement of the anesthesia team should ensure an appropriate level of postoperative care for these patients. LEVEL OF EVIDENCE: Level III, therapeutic study.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s11999-016-5056-

Investigating the clinical use of structured light plethysmography to assess lung function in children with neuromuscular disorders

BackgroundChildren and young people with neuromuscular disorders (NMD), such as Duchenne Muscular Dystrophy (DMD), develop progressive respiratory muscles weakness and pulmonary restriction. Pulmonary function monitoring of the decline in lung function allows for timely intervention with cough assist techniques and nocturnal non-invasive ventilation (NIV). NMD may find the measurement of lung function difficult using current techniques. Structured Light Plethysmography (SLP) has been proposed as a novel, non-contact, self-calibrating, non-invasive method of assessing lung function. The overarching aim of this study was to investigate the use of SLP as a novel method for monitoring respiratory function in children with neuromuscular disease.MethodsSLP thoraco-abdominal (TA) displacement was correlated with forced vital capacity measurements recorded by spirometry and the repeatability of the measurements with both methods examined. SLP tidal breathing parameters were investigated to assess the range and repeatability of regional right and left side TA displacement and rib cage and abdominal wall displacement.ResultsThe comparison of the FVC measured with SLP and with spirometry, while having good correlation (R = 0.78) had poor measurement agreement (95% limits of agreement: -1.2 to 1.2L) The mean relative contribution of right and left TA displacement in healthy controls was 50:50 with a narrow range. Repeatability of this measure with SLP was found to be good in healthy controls and moderate in NMD children with/without scoliosis but with a wider range. The majority of the control group displayed a predominant rib cage displacement during tidal breathing and those who displayed predominant abdominal wall displacement showed displacement of both regions close to 50:50 with similar results for the rib cage and abdomen. In comparison, children with NMD have a more variable contribution for all of these parameters. In addition, SLP was able to detect a reduction in abdominal contribution to TA displacement with age in the DMD group and detect paradoxical breathing in children with NMD. Using SLP tracings during tidal breathing we were able to identify three specific patterns of breathing amongst healthy individuals and in children with NMD.ConclusionsSLP is a novel method for measuring lung function that requires limited patient cooperation and may be especially useful in children with neuromuscular disorders. Measuring the relative contributions of the right and left chest wall and chest versus abdominal movements allows a more detailed assessment

Remission and recovery in the Treatment for Adolescents with Depression Study (TADS): acute and long-term outcomes.

OBJECTIVE: We examine remission rate probabilities, recovery rates, and residual symptoms across 36 weeks in the Treatment for Adolescents with Depression Study (TADS). METHOD: The TADS, a multisite clinical trial, randomized 439 adolescents with major depressive disorder to 12 weeks of treatment with fluoxetine, cognitive-behavioral therapy, their combination, or pill placebo. The pill placebo group, treated openly after week 12, was not included in the subsequent analyses. Treatment differences in remission rates and probabilities of remission over time are compared. Recovery rates in remitters at weeks 12 (acute phase remitters) and 18 (continuation phase remitters) are summarized. We also examined whether residual symptoms at the end of 12 weeks of acute treatment predicted later remission. RESULTS: At week 36, the estimated remission rates for intention-to-treat cases were as follows: combination, 60%; fluoxetine, 55%; cognitive-behavioral therapy, 64%; and overall, 60%. Paired comparisons reveal that, at week 24, all active treatments converge on remission outcomes. The recovery rate at week 36 was 65% for acute phase remitters and 71% for continuation phase remitters, with no significant between-treatment differences in recovery rates. Residual symptoms at the end of acute treatment predicted failure to achieve remission at weeks 18 and 36. CONCLUSIONS: Most depressed adolescents in all three treatment modalities achieved remission at the end of 9 months of treatment

RAG2's non-core domain contributes to the ordered regulation of V(D)J recombination

Variable (diversity) joining [V(D)J] recombination of immune gene loci proceeds in an ordered manner with D to J portions recombining first and then an upstream V joins that recombinant. We present evidence that the non-core domain of recombination activating gene (RAG) protein 2 is involved in the regulation of recombinatorial order. In mice lacking the non-core domain of RAG2 the ordered rearrangement is disturbed and direct V to D rearrangements are 10- to 1000-times increased in tri-partite immune gene loci. Some forms of inter-chromosomal translocations between TCRβ and TCRδ D gene segments are also increased in the core RAG2 animals as compared with their wild-type (WT) counterparts. In addition, the concise use of proper recombination signal sequences (RSSs) appears to be disturbed in the core RAG2 mice as compared with WT RAG2 animals

Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach.

Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5-Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers β-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and β-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a new predictor of CT responsiveness, and inhibition of Caspase-3, or antagonising downstream effectors of Caspase-3 paracrine signalling, such as COX-2 may improve patient outcomes following CT in advanced CRC