The efficacy of immune checkpoint blockade in gestational trophoblastic neoplasia (GTN) remains uncertain. We report the results of the GTN cohort of SWOG S1609 dual anti-CTLA-4 and anti-PD-1 ...blockade in rare tumors (DART).
This prospective, open-label phase II trial evaluated ipilimumab plus nivolumab across multiple rare tumor cohorts, including GTN. Eligible patients received nivolumab 240 mg, i.v. every 2 weeks and ipilimumab 1 mg/kg i.v. every 6 weeks. The primary endpoint was overall response rate ORR; complete response (CR) + partial response (PR) by quantitative serum beta human chorionic gonadotropin (β-hCG); secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.
Four patients with refractory GTN enrolled and received therapy. At 11 months of ongoing follow-up, 3 of 4 patients responded ORR = 75% (CR, 25%, n = 1, tumor mutation burden = 1 mutation/megabase; PD-L1 tumor proportion score = 50%); PR, 50%, n = 2). Responders included malignant gestational trophoblastic neoplasm (n = 1, CR, PFS 11+ months) and choriocarcinoma (n = 2, both PRs, PFS 10+ and 6+ months). One patient with epithelioid trophoblastic tumor experienced disease progression. The 6-month PFS was 75% 95% confidence interval (CI), 43%-100%, and the median PFS was not reached (range, 35-339+ days); all 4 patients were alive at last follow-up. Two patients experienced grade 3 immune-related toxicity (arthralgia and colitis); there were no grade ≥4 events.
Ipilimumab plus nivolumab demonstrated efficacy in chemotherapy-refractory GTN, an ultra-rare cancer affecting young women. Three of 4 patients achieved ongoing objective responses with a reasonable safety profile at 6-11+ months.
Muscle force production and power output in active males, regardless of the site of measurement (hand, leg, or back), are higher in the evening than in the morning. This diurnal variation is ...attributed to motivational, peripheral and central factors, and higher core and, possibly, muscle temperatures in the evening. This study investigated whether increasing morning rectal temperatures to evening resting values, by active or passive warm-ups, leads to muscle force production and power output becoming equal to evening values in motivated subjects. Ten healthy active males (mean ± SD: age, 21.2 ± 1.9 yrs; body mass, 75.4 ± 8 kg; height, 1.76 ± .06 m) completed the study, which was approved by the University Ethics Committee. The subjects were familiarized with the techniques and protocol and then completed four sessions (separated by at least 48 h): control morning (07:30 h) and evening (17:30 h) sessions (with an active 5-min warm-up) and then two further sessions at 07:30 h but proceeded by an extended active or passive warm-up to raise rectal temperature to evening values. These last two sessions were counterbalanced in order of administration. During each trial, three measures of handgrip strength, isokinetic leg strength measurements (of knee flexion and extension at 1.05 and 4.19 rad.s−1 through a 90° range of motion), and four measures of maximal voluntary contraction (MVC) on an isometric ergometer (utilizing the twitch-interpolation technique) were performed. Rectal and intra-aural temperatures, ratings of perceived exertion (RPE) and thermal comfort (TC) were measured. Measurements were made after the subjects had reclined for 30 min and after the warm-ups and prior to the measurement of handgrip and isokinetic and isometric ergometry. Muscle temperature was taken after the warm-up and immediately before the isokinetic and MVC measurements. Warm-ups were either active (cycle ergometer at 150 W) or passive (resting in a room at 35°C, relative humidity 45%). Data were analyzed using analysis of variance models with repeated measures. Rectal and intra-aural temperatures were higher at rest in the evening (.56°C and .74°C; p < .05) than in the morning, but there were no differences after the active or passive warm-ups, the subjects' ratings of thermal comfort reflecting this. Muscle temperatures also displayed significant diurnal variation, with higher values in the evening (∼.31°C; p < .05). Grip strength, isokinetic knee flexion for peak torque and peak power at 1.05 rad.s−1, and knee extension for peak torque at 4.19 rad.s−1 all showed higher values in the evening. All other measures of strength or power showed a trend to be higher in the evening ( .10 > p > .05). There was no significant effect of active or passive warm-ups on any strength or power variable, and subjects reported maximal values for effort for each strength measure. In summary, effects of time of day were seen in some measures of muscle performance but, in this population of motivated subjects, there was no evidence that increasing morning rectal temperature to evening values by active or passive warm-up increased muscle strength to evening values. (Author correspondence: B.J.Edwards@ljmu.ac.uk)
Chemistry: Atoms First 2e is a peer-reviewed, openly licensed introductory textbook produced through a collaborative publishing partnership between OpenStax and the University of Connecticut and ...UConn Undergraduate Student Government Association.This text is an atoms-first adaptation of OpenStax Chemistry 2e. The intention of “atoms-first” involves a few basic principles: first, it introduces atomic and molecular structure much earlier than the traditional approach, and it threads these themes through subsequent chapters. This approach may be chosen as a way to delay the introduction of material such as stoichiometry that students traditionally find abstract and difficult, thereby allowing students time to acclimate their study skills to chemistry. Additionally, it gives students a basis for understanding the application of quantitative principles to the chemistry that underlies the entire course. It also aims to center the study of chemistry on the atomic foundation that many will expand upon in a later course covering organic chemistry, easing that transition when the time arrives.
The second edition has been revised to incorporate clearer, more current, and more dynamic explanations, while maintaining the same organization as the first edition. Substantial improvements have been made in the figures, illustrations, and example exercises that support the text narrative. The first edition of Chemistry: Atoms First by OpenStax is available in web view here.
Muscle force production and power output in active males, regardless of the site of measurement (hand, leg, or back), are higher in the evening than the morning. This diurnal variation is attributed ...to motivational, peripheral, and central factors and higher core and, possibly, muscle temperatures in the evening. This study investigated whether decreasing evening resting rectal temperatures to morning values, by immersion in a water tank, leads to muscle force production and power output becoming equal to morning values in motivated subjects. Ten healthy active males (mean ± SD: age, 22.5 ± 1.3 yrs; body mass, 80.1 ± 7.8 kg; height, 1.72 ± 0.05 m) completed the study, which was approved by the local ethics committee of the university. The subjects were familiarized with the techniques and protocol and then completed three sessions (separated by at least 48 h): control morning (07:30 h) and evening (17:30 h) sessions (with an active 5-min warm-up on a cycle ergometer at 150 W) and then a further session at 17:30 h but preceded by an immersion in cold water (∼16.5 °C) to lower rectal temperature (Trec) to morning values. During each trial, three measures of grip strength, isokinetic leg strength measurements (of knee flexion and extension at 1.05 and 4.19 rad s−1 through a 90° range of motion), and three measures of maximal voluntary contraction (MVC) on an isometric dynamometer (utilizing the twitch-interpolation technique) were performed. Trec, rating of perceived exertion (RPE), and thermal comfort (TC) were also measured after the subjects had reclined for 30 min at the start of the protocol and prior to the measures for grip, isokinetic, and isometric dynamometry. Muscle temperature was taken after the warm-up or water immersion and immediately before the isokinetic and MVC measurements. Data were analyzed using general linear models with repeated measures. Trec values were higher at rest in the evening (by 0.37 °C; p < 0.05) than the morning, but values were no different from morning values immediately after the passive pre-cooling. However, Trec progressively decreased throughout the experiments, this being reflected in the subjects' ratings of thermal comfort. Muscle temperatures also displayed significant diurnal variation, with higher values in the evening (by 0.39 °C; p < 0.05). Right grip strength, isometric peak power, isokinetic knee flexion and extension for peak torque and peak power at 1.05 rad s−1, and knee extension for peak torque at 4.19 rad s−1 all showed higher values in the evening (a range of 3-14%), and all other measures of strength or power showed a statistical trend to be higher in the evening (0.10 > p > 0.05). Pre-cooling in the evening significantly reduced force or power variables towards morning values. In summary, effects of time of day were seen in some measures of muscle performance, in agreement with past research. However, in this population of motivated subjects, there was evidence that decreasing evening Trec to morning values by coldwater immersion decreased muscle strength to values similar to those found in the morning. It is concluded that diurnal changes in muscle performance are linked to diurnal changes in Trec. (Author correspondence: B.J.Edwards@ljmu.ac.uk)
Chemistry 2e Flowers, Paul; Theopold, Klaus; Langley, Richard ...
02/2019
eBook
Odprti dostop
Chemistry 2e is designed to meet the scope and sequence requirements of the two-semester general chemistry course. The textbook provides an important opportunity for students to learn the core ...concepts of chemistry and understand how those concepts apply to their lives and the world around them. The book also includes a number of innovative features, including interactive exercises and real-world applications, designed to enhance student learning. The second edition has been revised to incorporate clearer, more current, and more dynamic explanations, while maintaining the same organization as the first edition. Substantial improvements have been made in the figures, illustrations, and example exercises that support the text narrative. Changes made in Chemistry 2e are described in the preface to help instructors transition to the second edition. The first edition of Chemistry by OpenStax is available in web view here.
INTRODUCTION:To examine trends among women diagnosed with cervical carcinoma in New Orleans before and after the Affordable Care Act’s (ACA’s) Medicaid expansion was implemented in Louisiana in ...January 2016. Age at diagnosis, time since last doctor’s visit, progression free survival (PFS), and overall survival (OS) were analyzed between racial groups.
METHODS:Subjects with Medicaid coverage diagnosed with cervical cancer at an urban medical center between 2005-2019 were identified via hospital databases. Data were reviewed retrospectively and analyzed using SPSS.
RESULTS:451 subjects (310 black, 103 Caucasian, 38 Hispanic) were identified375 pre-ACA (2005-2016) and 76 post-ACA (2016-2019). All comparisons pre- vs post-ACA and results not statistically significant unless specified. Cumulative analysisage 49.9 vs 53.0 years (P<.001), doctor’s visit 18.7 vs 16.4 months (P<.001), PFS 52.5 vs 71.2 months (P<.001), and OS 57.6 vs 72.9 months (P<.001). Blackage 49.8 vs 49.0 years; doctor’s visit 19.2 vs 15.3 months; PFS 45.2 vs 36.9 months; OS 49.8 vs 39.5 months. Whiteage 51.9 vs 53.8 years; doctor’s visit 14.9 vs 11.0 months; PFS 50.4 vs 75.7 months (P<.006); OS 56.6 vs 77.3 months (P<.01). Hispanicage 50.2 vs 42.4 years (P<.001), doctor’s visit 23.0 vs 19.5 months; PFS 54.5 vs 72.4 months; OS 59.0 vs 75 months.
CONCLUSION:The ACA’s Medicaid expansion was associated with decreased time since last doctor’s visit and increased PFS and OS, notably in Hispanics and Caucasians. Hispanic women were diagnosed at earlier ages post-ACA which likely influenced early treatment and favorable prognoses. Conversely black women had decreased PFS and OS post-ACA which approached statistical significance, and they had the lowest PFS and OS pre-and post-ACA of all groups. This suggests access to care is not the only factor influencing cervical cancer outcomes in this disproportionately affected group.
INTRODUCTION:Female substance abusers are a vulnerable population facing numerous barriers to care, especially gynecological health. Access to contraception is a crucial part of women’s health; ...however, research on contraceptive use in substance abusers is limited. Our aim was to investigate contraceptive methods in a women’s substance abuse rehabilitation facility.
METHODS:Data was taken from 697 intake surveys of reproductive-aged women between 2013 and 2019. Analysis examined contraceptive use by sociodemographic variables. Trends were compared with data from 2015-2017 National Surveys of Family Growth and 2017 state-level data from the CDC.
RESULTS:The majority of women did not use contraceptives (40.3%), were sterilized (22.7%) or used condoms (21.1%). Compared to national and Louisiana-specific rates, this data reveals significantly higher proportions of no contraception and sterilization; conversely, there were lower rates of hormonal and long-acting reversible contraceptive methods (6.9; 4.9%). Substance-abusing women reported sterilization at a younger age (37) compared to national averages. 64.8% reported Medicaid enrollment; education and insurance were independent of contraceptive choice (X2=5.76, P=.22; X2=3.15, P=.53; P<.05).
CONCLUSION:Women in rehabilitation reported both a high rate of sterilization, and limited use of reversible contraceptives. Lack of variability in method could include amenorrhea from chronic substance use, mistrust of the healthcare system, and inadequate education on gynecological health. Residential rehabilitation facilities provide a unique opportunity for providers to deliver contraceptive education in a positive, encouraging environment, while women are focused on making positive lifestyle changes. Addressing this need would give these women greater autonomy over their health and fertility.
INTRODUCTION:Substance abuse is a growing problem among women, and is frequently accompanied by multiple gynecologic concerns. Residential substance abuse rehabilitation facilities offer an ...opportunity to address those concerns. The purpose of this report is to examine the impact of an all-volunteer, medical student-run clinic with faculty supervision within a non-profit, inner-city womenʼs residential substance abuse rehabilitation facility.
METHODS:625 clients were admitted, regardless of financial status, to a 70-bed residential substance abuse rehabilitation facility between 2016 and mid-2018. Data including Pap smears, Human Papillomavirus (HPV) infection, and sexually transmitted infection testing were analyzed.
RESULTS:From January 2016 through August 2018, 175/625 (28.0%) clients accepted Pap testing. 52/175 (29.7%) had an abnormal result, defined as Trichomonas infection, HPV infection, or premalignant or malignant lesion. 240/625 (38.4%) clients accepted Gonorrhea/Chlamydia testing, and 6 were identified as having Gonorrhea or Chlamydia. In 2018 alone, Pap testing identified 7/44 (15.9%) clients as having premalignant or malignant lesions, including one case of squamous cell carcinoma. 9/24 (37.5%) had a high-risk HPV strain. 7/44 (15.9%) had Trichomonas. Clients also received counseling regarding personal health awareness and reduction of high-risk behaviors.
CONCLUSION:The use of a student-run clinic to provide gynecologic services within a residential substance abuse rehabilitation facility has a major impact and is cost-efficient. Many clients have no other opportunity to obtain instruction on health awareness and high-risk behavior, as well as diagnosis and treatment of abnormal Pap smears and STIs. This model allows non-profit facilities to provide an otherwise unaffordable level of care.
Abstract Objective Intraperitoneal (IP) chemotherapy prolongs survival in optimally reduced ovarian cancer patients. For patients in whom optimal debulking cannot be achieved, one could incorporate ...IP therapy post-operatively if the cancer was optimally debulked following neoadjuvant chemotherapy. We sought to evaluate overall survival (OS), progression-free survival (PFS), percent of patients optimally debulked and toxicity in patients treated with this strategy. Methods Women with adenocarcinoma by biopsy or cytology with stage III/IV (pleural effusions only) epithelial ovarian, fallopian tube or primary peritoneal carcinoma that presented with bulky disease were treated with neoadjuvant intravenous (IV) paclitaxel 175 mg/m2 and carboplatin AUC 6 q 21 days × 3 cycles followed by surgery (if ≥ 50% decrease in CA125). If optimally debulked they received IV paclitaxel 175 mg/m2 and IP carboplatin AUC 5 (day 1) and IP paclitaxel 60 mg/m2 (day 8) q 28 days × 6 cycles. Results Sixty-two patients were registered. Four were ineligible. Fifty-six were evaluated for neoadjuvant chemotherapy toxicities. One patient died of pneumonia. Five patients had grade 4 toxicity, including neutropenia (3), anemia, leukopenia, anorexia, fatigue, muscle weakness, respiratory infection, and cardiac ischemia. Thirty-six patients had debulking surgery. Two had grade 4 hemorrhage. Twenty-six patients received post-cytoreduction chemotherapy. Four had grade 4 neutropenia. At a median follow-up of 21 months, median PFS is 21 months and median OS is 32 months for all 58 patients. PFS and OS for the 26 patients who received IV/IP chemotherapy is 29 and 34 months respectively. Conclusions These results compare favorably with other studies of sub-optimally debulked patients.
We have investigated the magnitude of circadian variation in Isokinetic and Isometric strength of the knee extensors and flexors, as well as back squat and bench press performance using the MuscleLab ...force velocity transducer. Ten resistance-trained males (mean±SD: age 21.5 ± 1.1 years; body mass 78.3 ± 5.2 kg; height 1.71 ± 0.07 m) underwent a) three to four familiarization sessions on each dynamometer and b) four sessions at different times of day (03:00, 09:00, 15:00 and 21:00 h). Each session was administered in a counterbalanced order and included a period when Perceived onset of mood states (POMS), then rectal and muscle temperature (T
, T
) was measured at rest, after which a 5-min standardized 150 W warm-up was performed on a cycle ergometer. Once completed, Isokinetic (60 and 240°·s
for extension and flexion) and Isometric dynamometry with peak torque (PT), time-to-peak-torque (tPT) and peak force (PF) and % activation was measured. Lastly, T
and T
were measured before the bench press (at 30, 50 and 70 kg) and back squat (at 40, 60 and 80 kg) exercises. A linear encoder was attached to an Olympic bar used for the exercises and average force (AF), peak velocity (PV) and time-to-peak-velocity (tPV) were measured (MuscleLab software; MuscleLab Technology, Langesund, Norway) during the concentric phase of the movements. Five-min recovery was allowed between each set with three repetitions being completed. General linear models with repeated measures and cosinor analysis were used to analyse the data. Values for T
and T
at rest were higher in the evening compared to morning values (Acrophase Φ: 16:35 and 17:03 h, Amplitude A: 0.30 and 0.23°C, Mesor M: 36.64 and 37.43°C,
< 0.05). Vigor, happy and fatigue mood states responses showed Φ 16:11 and 16:03 h and 02:05 h respectively. Circadian rhythms were apparent for all variables irrespective of equipment used where AF, PF and PT values peaked between 16:18 and 18:34 h; PV, tPV and tPT peaked between 05:54 and 08:03 h (
< 0.05). In summary, circadian rhythms in force output (force, torque, power, and velocity) were shown for isokinetic, isometric dynamometers and complex multi-joint movements (using a linear encoder); where tPV and tPT occur in the morning compared to the evening. Circadian rhythms in strength can be detected using a portable, low-cost instrument that shows similar cosinor characteristics as established dynamometers. Hence, muscle-strength can be measured in a manner that is more directly transferable to the world of athletic and sports performance.
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