Activity-Specific Effects of Fatigue Protocols May Influence Landing Kinematics: A Pilot Study

International Journal of Exercise Science 6(3) : 242-249, 2013. Fatigue is a common neuromuscular factor examined in relation to risk of ACL injury. Unfortunately, variations between the protocols used to induce fatigue in studies examining this phenomenon may have contributed to reported inconsistencies in the effects of fatigue on movements with high-risk of ACL injury. In addition, the ecological validity of fatigue experienced as a result of protocols commonly administered in the experimental setting is unclear. The purpose of this study was to examine the ecological validity, using basketball competition as the criterion measure, of two fatigue protocols commonly used to study the effect of fatigue on ACL injury risk. One male basketball player with competitive collegiate experience was recruited to participate in this study. Three dimensional angular kinematics of the lower extremity at the point of peak knee flexion were measured during a jump landing task before and after the completion of three fatigue protocols: a basketball game, a unilateral squatting and drop landing fatigue protocol, and a unilateral isokinetic knee flexion/extension fatigue protocol. We observed significant (p\u3c.05) differences between fatigue protocols in knee flexion, knee rotation, knee abduction, hip rotation, and hip abduction during the landing task. In this study the fatigue-induced changes in landing biomechanics experienced as a result of basketball competition were not like those observed in the two fatigue protocols tested. These findings suggest that the effects of fatigue on ACL injury risk may be activity-specific and future investigations may benefit from the development of ecologically valid sport-specific fatigue protocols

The effects of conflict role and intensity on preschoolers’ expectations about peer conflict

Using a puppet procedure depicting hypothetical conflict involving the participant and a peer, 96 preschoolers’ (48 boys and 48 girls; M 1/4 5.14 years, SD 1/4 0.78 years) expectations about peer conflict were assessed as a function of their role in the conflict (i.e., initiator of or responder to initial provocation) and the intensity level of the conflict. Initiators of conflict expected less conflict escalation and subsequent problems with the same peer from the conflict than did responders, particularly following low-intensity conflict. Findings also indicated that, for low-intensity but not high-intensity conflict, girls expected the same peer to provoke them during a subsequent interaction more often than did boys. Results provide further support for assessing preschoolers’ understanding of conflict and are consistent with previous work demonstrating a self-serving bias in young children’s perceptions and reports of their conflicts with other children. Moreover, findings are discussed in terms of their implications for the development of peer relations.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer.

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

The psychometric utility of the midpoint on a Likert scale

Among Likert scale research spanning a number of disciplines are studies reaching conflicting conclusions about the theoretical and psychometric necessity of the midpoint. Typically, midpoint responders have been classified as ambivalent, indifferent, and uncertain. Theoretically, a midpoint response should represent ambivalent attitudes--those who are familiar with what they are rating and have equal feelings of agreement and disagreement. Item Response Theory (IRT) research has not supported the utility of the midpoint. The theory underlying this dissertation is that by providing a second nondirectional category (Don\u27t Know), the midpoint (Undecided) would function more like a theoretical true midpoint, thereby improving scale properties. Hypotheses were studied using Bock\u27s (1972) Nominal Response and Samejima\u27s (1969) Graded Response IRT models. Comparisons of option characteristic curves, discrimination parameters, information functions, relative efficiency, and model fit were made between Scale A (5 alternatives with additional sixth Don\u27t Know alternative) and Scale B (5 alternatives) across 18 items in two demographically similar independent samples. Findings generally supported the hypothesis that providing a sixth Don\u27t Know alternative improves the operating characteristics of the middle category, as well as other categories. Scale A items tended to have discrimination parameters and scale information exceeding that of Scale B, particularly on items measuring general attitudes as opposed to specific behavioral outcomes. The Undecided category had highest probabilities at low negative to middle levels of theta in both scales, and Undecided category Option Characteristic Curves tended to peak above that of other categories, more so on Scale A. Both nondirectional categories appeared to be scale dependent. The Don\u27t Know response option consistently peaked to the left of the scale. Implications are that by using IRT to understand the properties of different options, psychometricians can develop more efficient measures of attitude and practitioners can gain a more precise understanding of the meaning attached to different options. Limitations and future research are discussed