108 research outputs found
Jim Crow Riding High: The Latest Assaults on African American Voting Rights
The aftermath of the shooting of Trayvon Martin raises serious issues about a possible double standard between the enforcement of civil rights for African-Americans and white Americans. This paper discusses two key voting rights â hence, civil rights - enforcement issues, voter suppression and disenfranchisement. While the 1965 Voting Rights Act guarantees the right to vote to all qualified Americans, there is substantial evidence that this right is often denied minorities. It has included strenuous efforts to suppress the black vote. How extensive is this effort, and what effect did suppression have on recent elections, including the Presidential election of 2012? Legislative districting can create âfunctional disenfranchisementâ for African-Americans, by which ostensibly they retain the right to vote, but the meaning and instrumentality of that vote is rendered null and void. To what extent did the 2010 round of redistricting in Florida and other states promote functional disenfranchisement of African-Americans, the effect of which could be to minimize their voice in and impact on electoral politics
Jim Crow Riding High: The Latest Assaults on African American Voting Rights
The aftermath of the shooting of Trayvon Martin raises serious issues about a possible double standard between the enforcement of civil rights for African-Americans and white Americans. This paper discusses two key voting rights â hence, civil rights - enforcement issues, voter suppression and disenfranchisement. While the 1965 Voting Rights Act guarantees the right to vote to all qualified Americans, there is substantial evidence that this right is often denied minorities. It has included strenuous efforts to suppress the black vote. How extensive is this effort, and what effect did suppression have on recent elections, including the Presidential election of 2012? Legislative districting can create âfunctional disenfranchisementâ for African-Americans, by which ostensibly they retain the right to vote, but the meaning and instrumentality of that vote is rendered null and void. To what extent did the 2010 round of redistricting in Florida and other states promote functional disenfranchisement of African-Americans, the effect of which could be to minimize their voice in and impact on electoral politics
Considerations for Management of Longitudinal Melanonychia During the COVID-19 Pandemic: An International Perspective
To the editor: 34 Longitudinal melanonychia (LM) is the presenting sign of nail unit melanoma (NUM) in 2/3 35 of cases and is therefore among the most important conditions managed by dermatologists. In 36 normal times, referral for LM would prompt an expedited appointment for clinical 37 examination and dermoscopy.1 However, due to SARS-CoV-2, dermatologists have been 38 asked to reconsider âurgent/emergencyâ conditions. The COVID-19 pandemic has propelled 39 physicians to unexpectedly adopt telemedicine without adequate guidance for managing LM 40 patients
Defining the Differences Between Episodic Migraine and Chronic Migraine
Chronic migraine (CM) and episodic migraine (EM) are part of the spectrum of migraine disorders, but they are distinct clinical entities. Population-based studies have shown that those with CM demonstrate higher individual and societal burden because they are significantly more disabled than those with EM and have greater impaired quality of life both inside and outside the home. Proper diagnosis of both conditions requires clearly defined clinical criteria. Diagnosis enables the initiation of appropriate treatments and risk-factor modification, which ultimately improve functional status and quality of life for persons with migraine. Recognizing that both disorders are on the spectrum of migraine, this review serves as a guide to define the disease state of CM as distinct from EM in terms of clinical, epidemiological, sociodemographic, and comorbidity profiles
Evaluation of Unmeshed and 1:1 Meshed AlloDerm Bolsters for Stapled Rectal Anastomoses in a Porcine Model
Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor
Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins
Back to the Future: Lessons from Knowledge Engineering Methodologies for Chatbot Design and Development
Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial
BACKGROUND
Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone.
METHODS
Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOCâ+âZA), standard of care plus docetaxel (SOCâ+âDoc), or standard of care with both zoledronic acid and docetaxel (SOCâ+âZAâ+âDoc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544).
FINDINGS
2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOCâ+âZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOCâ+âDoc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOCâ+âZAâ+âDoc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOCâ+âZA, 288 (52%) receiving SOCâ+âDoc, and 269 (52%) receiving SOCâ+âZAâ+âDoc.
INTERPRETATION
Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy.
FUNDING
Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research
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