Prognostic indicators in patients presenting with the nephrotic syndrome

Prognostic indicators in patients presenting with the nephrotic syndrome. Clinical data from 246 patients presenting with a nephrotic syndrome and biopsy-proven glomerular disorder were analyzed, using statistical survival techniques, to determine which of several variables (sex, age, plasma creatinine, diastolic blood pressure and 24-hour urinary protein loss) were associated with subsequent end-stage renal failure. The best prediction of outcome could be made at one year (N = 121); then plasma creatinine (P < 0.001) and heavy proteinuria (P = 0.049) were the best determinants. For a given plasma creatinine level, heavy urinary protein was associated with a worse outcome. The incidence of end-stage renal failure was greatest three to four years from the date edema first developed. Plasma creatinine and urinary protein values, collected four-monthly throughout the study period, were analyzed as time-dependent covariates. A relationship was found between the prevailing risk of renal failure and earlier heavy proteinuria (P < 0.001). Spontaneous complete remission of proteinuria was associated with a highly favorable outcome (P = 0.001) and normal, or impaired but stable, renal function

The Grizzly, November 22, 1994

Pew Roundtable Discusses Priorities at Ursinus • Clinton Wavers on School Prayer • Letters to the Editor: Parent Shows Concern Over Alcohol • Man Arrested for Threatening Children • Class of \u2798 Update • Iraq Recognizes Kuwait • Final Exam Schedule • Berman Features Watercolor Exhibit • Lady Bears Preseason Outlook • Ursinus\u27 All-Centennial Conference Performershttps://digitalcommons.ursinus.edu/grizzlynews/1348/thumbnail.jp

Mycoplasma genitalium: An Emerging Cause of Sexually Transmitted Disease in Women

Mycoplasma genitalium is an emerging sexually transmitted pathogen implicated in urethritis in men and several inflammatory reproductive tract syndromes in women including cervicitis, pelvic inflammatory disease (PID), and infertility. This comprehensive review critically examines epidemiologic studies of M. genitalium infections in women with the goal of assessing the associations with reproductive tract disease and enhancing awareness of this emerging pathogen. Over 27,000 women from 48 published reports have been screened for M. genitalium urogenital infection in high- or low-risk populations worldwide with an overall prevalence of 7.3% and 2.0%, respectively. M. genitalium was present in the general population at rates between those of Chlamydia trachomatis and Neisseria gonorrhoeae. Considering more than 20 studies of lower tract inflammation, M. genitalium has been positively associated with urethritis, vaginal discharge, and microscopic signs of cervicitis and/or mucopurulent cervical discharge in seven of 14 studies. A consistent case definition of cervicitis is lacking and will be required for comprehensive understanding of these associations. Importantly, evidence for M. genitalium PID and infertility are quite convincing and indicate that a significant proportion of upper tract inflammation may be attributed to this elusive pathogen. Collectively, M. genitalium is highly prevalent in high- and low-risk populations, and should be considered an etiologic agent of select reproductive tract disease syndromes in women

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

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

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

Interdecadal foredune changes along the Southeast Australian coastline: 1942-2014

Foredunes are important features within coastal landscapes, yet there are relatively few medium to long-term studies on how they evolve and change over time. This study of Australia\u27s New SouthWales (NSW) foredunes has used 70 years of aerial photographs (or photogrammetry) and recent Light Detection and Ranging (LiDAR) datasets to assess multi-decadal fluctuations in foredune morphology. It was shown that over the past 70 years NSW foredunes have exhibited considerable spatial variation, ranging from accretion/aggradation to recession. Those sites that accreted predominantly extended seaward as new incipient dunes, gaining a maximum of 235 m3 m-1 in sand volume over the study period (for the entire dune system). These sites were commonly found in the north of the state, within closed sediment compartments, and with strong onshore (and alongshore) wind climates present (increasing the potential for aeolian sand transport). Stable foredunes were those that remained within +/- 50 m3 m-1 of their initial volume and managed to recover from the various storm impacts over the study period. The majority of these sites were found within the central to southern half of the state, behind embayed beaches, and within leaky sediment compartments, or those that have estuarine sinks. Finally, those foredunes in recession have retreated landwards and/or have reduced in height or width, and lost up to 437 m3 m-1 of sand volume over the study period. There was no clear spatial trend for these sites; however, generally they were found in compartments that had unusual orientations, had disruptions in longshore drift/cross shore sand delivery (i.e., rocky reefs), or were being impacted by humans (i.e., the installation of river training walls, sand bypassing systems, or coastal management programs). This study has shown that NSW foredunes have undergone substantial recent changes and, by understanding their past history, will provide better insight into how they can be managed into the future

Rapid shoreline progradation followed by vertical foredune building at Pedro Beach, southeastern Australia

At Pedro Beach on the southeastern coast of Australia a series of foredune ridges provides an opportunity to explore the morphodynamic paradigm as it applies to coastal barrier systems using optically stimulated luminescence (OSL) dating, ground penetrating radar (GPR) and airborne LiDAR topography. A series of sandy dune-capped ridges, increasing in height seawards, formed from c. 7000 years ago to c. 3900 years ago. During this time the shoreline straightened as the embayment filled and accommodation space for Holocene sediments diminished. Calculation of Holocene sediment accumulation above mean sea level utilising airborne LiDAR topography shows a decline in average sediment supply over this time period coupled with a decrease in shoreline progradation rate from 1.2 m/yr to 0.38 m/yr. The average ridge \u27exposure lifetime\u27 during this period increases resulting in higher ridges as dune-forming processes have longer to operate. Increasing exposure to wave and wind energy also appears to have resulted in higher ridges as the sheltering effect of marginal headlands was diminished. An inherited disequilibrium shoreface profile will drive onshore accumulation of sandy sediments forming a prograded barrier; however, if there is no longer \u27accommodation space\u27 for sediment, this will be an overriding factor causing the cessation of progradation, as occurred c. 3900 years ago at Pedro Beach. Excess sediment in the nearshore zone after 3900 years ago may have been moved northward to nourish downdrift beaches in the compartment. A high outer foredune has formed through vertical accretion after 500 years ago, evidenced by GPR subsurface structures and OSL ages, with a distinct period of vertical and lee slope accretion and dated to the period 1890-1930 AD. The increased dune sediment transport resulting in foredune building is attributed to recent human disturbance. 2018 John Wiley & Sons, Ltd