A neural network model was previously developed to predict melatonin rhythms accurately from blue light and skin temperature recordings in individuals on a fixed sleep schedule. This study aimed to ...test the generalizability of the model to other sleep schedules, including rotating shift work. Ambulatory wrist blue light irradiance and skin temperature data were collected in 16 healthy individuals on fixed and habitual sleep schedules, and 28 rotating shift workers. Artificial neural network models were trained to predict the circadian rhythm of (i) salivary melatonin on a fixed sleep schedule; (ii) urinary aMT6s on both fixed and habitual sleep schedules, including shift workers on a diurnal schedule; and (iii) urinary aMT6s in rotating shift workers on a night shift schedule. To determine predicted circadian phase, center of gravity of the fitted bimodal skewed baseline cosine curve was used for melatonin, and acrophase of the cosine curve for aMT6s. On a fixed sleep schedule, the model predicted melatonin phase to within ± 1 hour in 67% and ± 1.5 hours in 100% of participants, with mean absolute error of 41 ± 32 minutes. On diurnal schedules, including shift workers, the model predicted aMT6s acrophase to within ± 1 hour in 66% and ± 2 hours in 87% of participants, with mean absolute error of 63 ± 67 minutes. On night shift schedules, the model predicted aMT6s acrophase to within ± 1 hour in 42% and ± 2 hours in 53% of participants, with mean absolute error of 143 ± 155 minutes. Prediction accuracy was similar when using either 1 (wrist) or 11 skin temperature sensor inputs. These findings demonstrate that the model can predict circadian timing to within ± 2 hours for the vast majority of individuals on diurnal schedules, using blue light and a single temperature sensor. However, this approach did not generalize to night shift conditions.
Nurses experience poor sleep and high stress due to demanding work environments. Night shift work is common among nurses and may exacerbate stress–sleep associations. We examined bidirectional ...associations between daily stress and sleep, and moderation by recent shift worker status and daily work schedule among nurses. Participants were 392 nurses (92% female; 78% White, mean age = 39.54, SD = 11.15) who completed 14 days of electronic sleep diaries and actigraphy. They simultaneously completed assessments of daily stress and work schedule upon awakening (day shift vs. night shift work between 9 p.m.–6 a.m. vs. off work). Participants were classified as recent night shift workers if they worked at least one night shift during the past 14 days (n = 101; 26%). In the entire sample, greater daily stress predicted shorter self‐reported total sleep time and lower self‐reported sleep efficiency that night. Shorter self‐reported and actigraphy total sleep time and lower self‐reported sleep efficiency predicted higher next‐day stress. Compared with recent night shift workers, day workers reported higher stress after nights with shorter total sleep time. Stress‐sleep associations mostly did not vary by nurses’ daily work schedule. Sleep disturbances and stress may unfold in a toxic cycle and are prime targets for tailored interventions among nurses. Night shift workers may be less susceptible to the effects of short sleep on next‐day stress. Research is needed to understand the short‐ and long‐term effects of shift work and address the unique sleep challenges nurses face.
Shift work with circadian disruption has been considered as a carcinogenic risk factor for skin cancer. The few prior studies that investigated the association between shift work and skin cancer have ...inconclusive results. Our main objective was to evaluate the associations between shift work and the risks of different types of skin cancer. We systematically searched PubMed, Web of Science, Cochrane Library, EMBASE and Science Direct until October 2018 for studies that included a relationship between shift work and skin cancer. Our search yielded 193 articles and 9 studies met the criteria for our review. The included studies involved 3,579,147 participants and 17,308 skin cancer cases. Overall, ever shift work, was associated with increased risk of melanoma (RR = 1.10, 95% CI = 1.05-1.16) and a significant decrease in the risk of BCC (RR = 0.90, 95% CI = 0.88-0.93). No association between shift work and the risk of SCC was detected. Interestingly, our dose response analysis demonstrated that the risk of melanoma cumulatively increases by 2% for every year of shift work (RR = 1.02; 95% CI = 1.00-1.03). In conclusion, shift work is associated with increased risk of melanoma and deceased risk of BCC. Further studies are needed to confirm our findings and to elucidate the related potential biological mechanisms.
Although memory impairment is the main symptom of Alzheimer's disease (AD), language impairment can be an important marker. Relatively few studies of language in AD quantify the impairments in ...connected speech using computational techniques.
We aim to demonstrate state-of-the-art accuracy in automatically identifying Alzheimer's disease from short narrative samples elicited with a picture description task, and to uncover the salient linguistic factors with a statistical factor analysis.
Data are derived from the DementiaBank corpus, from which 167 patients diagnosed with "possible" or "probable" AD provide 240 narrative samples, and 97 controls provide an additional 233. We compute a number of linguistic variables from the transcripts, and acoustic variables from the associated audio files, and use these variables to train a machine learning classifier to distinguish between participants with AD and healthy controls. To examine the degree of heterogeneity of linguistic impairments in AD, we follow an exploratory factor analysis on these measures of speech and language with an oblique promax rotation, and provide interpretation for the resulting factors.
We obtain state-of-the-art classification accuracies of over 81% in distinguishing individuals with AD from those without based on short samples of their language on a picture description task. Four clear factors emerge: semantic impairment, acoustic abnormality, syntactic impairment, and information impairment.
Modern machine learning and linguistic analysis will be increasingly useful in assessment and clustering of suspected AD.
Sorafenib is the recommended treatment for patients with advanced hepatocellular carcinoma. We aimed to compare the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) ...with yttrium-90 (90Y) resin microspheres in patients with hepatocellular carcinoma.
SARAH was a multicentre, open-label, randomised, controlled, investigator-initiated, phase 3 trial done at 25 centres specialising in liver diseases in France. Patients were eligible if they were aged at least 18 years with a life expectancy greater than 3 months, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, Child-Pugh liver function class A or B score of 7 or lower, and locally advanced hepatocellular carcinoma (Barcelona Clinic Liver Cancer BCLC stage C), or new hepatocellular carcinoma not eligible for surgical resection, liver transplantation, or thermal ablation after a previously cured hepatocellular carcinoma (cured by surgery or thermoablative therapy), or hepatocellular carcinoma with two unsuccessful rounds of transarterial chemoembolisation. Patients were randomly assigned (1:1) by a permutated block method with block sizes two and four to receive continuous oral sorafenib (400 mg twice daily) or SIRT with 90Y-loaded resin microspheres 2–5 weeks after randomisation. Patients were stratified according to randomising centre, ECOG performance status, previous transarterial chemoembolisation, and presence of macroscopic vascular invasion. The primary endpoint was overall survival. Analyses were done on the intention-to-treat population; safety was assessed in all patients who received at least one dose of sorafenib or underwent at least one of the SIRT work-up exams. This study has been completed and the final results are reported here. The trial is registered with ClinicalTrials.gov, number NCT01482442.
Between Dec 5, 2011, and March 12, 2015, 467 patients were randomly assigned; after eight patients withdrew consent, 237 were assigned to SIRT and 222 to sorafenib. In the SIRT group, 53 (22%) of 237 patients did not receive SIRT; 26 (49%) of these 53 patients were treated with sorafenib. Median follow-up was 27·9 months (IQR 21·9–33·6) in the SIRT group and 28·1 months (20·0–35·3) in the sorafenib group. Median overall survival was 8·0 months (95% CI 6·7–9·9) in the SIRT group versus 9·9 months (8·7–11·4) in the sorafenib group (hazard ratio 1·15 95% CI 0·94–1·41 for SIRT vs sorafenib; p=0·18). In the safety population, at least one serious adverse event was reported in 174 (77%) of 226 patients in the SIRT group and in 176 (82%) of 216 in the sorafenib group. The most frequent grade 3 or worse treatment-related adverse events were fatigue (20 9% vs 41 19%), liver dysfunction (25 11% vs 27 13%), increased laboratory liver values (20 9% vs 16 7%), haematological abnormalities (23 10% vs 30 14%), diarrhoea (three 1% vs 30 14%), abdominal pain (six 3% vs 14 6%), increased creatinine (four 2% vs 12 6%), and hand-foot skin reaction (one <1% vs 12 6%). 19 deaths in the SIRT group and 12 in the sorafenib group were deemed to be treatment related.
In patients with locally advanced or intermediate-stage hepatocellular carcinoma after unsuccessful transarterial chemoembolisation, overall survival did not significantly differ between the two groups. Quality of life and tolerance might help when choosing between the two treatments.
Sirtex Medical Inc.
After curative resection, the prognosis of gastroesophageal adenocarcinoma is poor. This phase III trial was designed to evaluate the benefit in overall survival (OS) of perioperative fluorouracil ...plus cisplatin in resectable gastroesophageal adenocarcinoma.
Overall, 224 patients with resectable adenocarcinoma of the lower esophagus, gastroesophageal junction (GEJ), or stomach were randomly assigned to either perioperative chemotherapy and surgery (CS group; n = 113) or surgery alone (S group; n = 111). Chemotherapy consisted of two or three preoperative cycles of intravenous cisplatin (100 mg/m(2)) on day 1, and a continuous intravenous infusion of fluorouracil (800 mg/m(2)/d) for 5 consecutive days (days 1 to 5) every 28 days and three or four postoperative cycles of the same regimen. The primary end point was OS.
Compared with the S group, the CS group had a better OS (5-year rate 38% v 24%; hazard ratio HR for death: 0.69; 95% CI, 0.50 to 0.95; P = .02); and a better disease-free survival (5-year rate: 34% v 19%; HR, 0.65; 95% CI, 0.48 to 0.89; P = .003). In the multivariable analysis, the favorable prognostic factors for survival were perioperative chemotherapy (P = .01) and stomach tumor localization (P < .01). Perioperative chemotherapy significantly improved the curative resection rate (84% v 73%; P = .04). Grade 3 to 4 toxicity occurred in 38% of CS patients (mainly neutropenia) but postoperative morbidity was similar in the two groups.
In patients with resectable adenocarcinoma of the lower esophagus, GEJ, or stomach, perioperative chemotherapy using fluorouracil plus cisplatin significantly increased the curative resection rate, disease-free survival, and OS.
Background & Aims The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for ulcerative colitis (UC) have not been evaluated previously. Methods This ...randomized, double-blind trial evaluated the efficacy and safety of 16 weeks of treatment with infliximab monotherapy, azathioprine monotherapy, or the 2 drugs combined in tumor necrosis factor-α antagonist-naive adults with moderate to severe UC. Patients were assigned randomly to receive intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, and 14 plus daily oral placebo capsules; oral azathioprine 2.5 mg/kg daily plus placebo infusions on the infliximab schedule; or combination therapy with the 2 drugs. Corticosteroid-free clinical remission (primary end point, week 16) was evaluated at weeks 8 and 16. The study was terminated before the enrollment target was reached. Results A total of 239 patients were included in efficacy analyses. Baseline characteristics were similar between treatment groups. Corticosteroid-free remission at week 16 was achieved by 39.7% (31 of 78) of patients receiving infliximab/azathioprine, compared with 22.1% (17 of 77) receiving infliximab alone ( P = .017) and 23.7% (18 of 76) receiving azathioprine alone ( P = .032). Mucosal healing at week 16 occurred in 62.8% (49 of 78) of patients receiving infliximab/azathioprine, compared with 54.6% (42 of 77) receiving infliximab ( P = .295) and 36.8% (28 of 76) receiving azathioprine ( P = .001). Serious infections occurred in 2 patients (1 patient receiving infliximab, and 1 patient receiving azathioprine). Conclusions Anti–tumor necrosis factor-α–naive patients with moderate to severe UC treated with infliximab plus azathioprine were more likely to achieve corticosteroid-free remission at 16 weeks than those receiving either monotherapy. Combination therapy led to significantly better mucosal healing than azathioprine monotherapy. ClinicalTrials.gov number, NCT00537316.
Wheat blast, caused by the fungus Magnaporthe oryzae pathotype Triticum (MoT), constitutes one of the major obstacles to the expansion of wheat production in Bangladesh. In the absence of resistant ...variety, fungicide control is the first-hand effort. Determining an effective and economic fungicide spray schedule in controlling blast disease of wheat was aimed. Ten fungicides were tested during two consecutive cropping seasons of 2018-2019 to 2019-2020. The wheat plants of blast susceptible cultivar BARI Gom 26 were inoculated with spores (107 spores ml-1) of MoT at pre-heading stage of wheat (52 days age). Fungicides were applied both before inoculation and after the appearance of blast symptoms in cocktail for three times starting from booting of wheat at 7 days interval. Plants received the combination of Filia (Tricyclazole 40% + Propiconazole 12.5%) and Seltima (Pyraclostrobin 10%) had significantly lower blast incidence and severity (1.23% and 3.33%) against untreated plants. Cocktail of Nativo and Trooper (Tricyclazole 75 wp) proved 2nd best curative measure. Application of Nativo (Tebuconazole 50% + Trifloxystrobin 25%) alone ranked third in its efficacy. The fungicide spray schedule covered booting, pre-heading and heading stages of wheat. The results indicate a mixture of Tebuconazole + Tricyclazole + Pyraclostrobin is more effective (97% blast reduction) and economic (BCR 1.45) than a single compound application in reducing incidence and severity of wheat blast.
Int. J. Agril. Res. Innov. Tech. 11(1): 10-16, June 2021
Standard-of-care treatment for patients with newly diagnosed multiple myeloma includes combination therapies for patients who are not eligible for autologous stem-cell transplantation. At the primary ...analysis for progression-free survival of the phase 3 ALCYONE trial, progression-free survival was significantly longer with daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in patients with transplant-ineligible, newly diagnosed multiple myeloma. Here we report updated efficacy and safety results from a prespecified, interim, overall survival analysis of ALCYONE with more than 36 months of follow-up.
ALCYONE was a multicentre, randomised, open-label, active-controlled, phase 3 trial that enrolled patients between Feb 9, 2015, and July 14, 2016, at 162 sites in 25 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were eligible for inclusion if they had newly diagnosed multiple myeloma and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or because of substantial comorbidities. Patients were randomly assigned in a 1:1 ratio and by permuted block randomisation to receive D-VMP or VMP. An interactive web-based randomisation system was used. Randomisation was stratified by International Staging System disease stage, geographical region, and age. There was no masking to treatment assignments. All patients received up to nine 6-week cycles of subcutaneous bortezomib (1·3 mg/m2 of body surface area on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycle one and on days 1, 8, 22, and 29 of cycles two through nine), oral melphalan (9 mg/m2 once daily on days 1 through 4 of each cycle), and oral prednisone (60 mg/m2 once daily on days 1 through 4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg of bodyweight, once weekly during cycle one, once every 3 weeks in cycles two through nine, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival, which has been reported previously. Results presented are from a prespecified interim analysis for overall survival. The primary analysis population (including for overall survival) was the intention-to-treat population of all patients who were randomly assigned to treatment. The safety population included patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02195479.
706 patients were randomly assigned to treatment groups (350 to the D-VMP group, 356 to the VMP group). At a median follow-up of 40·1 months (IQR 37·4–43·1), a significant benefit in overall survival was observed for the D-VMP group. The hazard ratio (HR) for death in the D-VMP group compared with the VMP group was 0·60 (95% CI 0·46–0·80; p=0·0003). The Kaplan-Meier estimate of the 36-month rate of overall survival was 78·0% (95% CI 73·2–82·0) in the D-VMP group and 67·9% (62·6–72·6) in the VMP group. Progression-free survival, the primary endpoint, remained significantly improved for the D-VMP group (HR 0·42 0·34–0·51; p<0·0001). The most frequent adverse events during maintenance daratumumab monotherapy in patients in the D-VMP group were respiratory infections (54 19% of 278 patients had upper respiratory tract infections; 42 15% had bronchitis, 34 12% had viral upper respiratory tract infections), cough (34 12%), and diarrhoea (28 10%).
D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. With more than 3 years of follow-up, the D-VMP group continued to show significant improvement in progression-free survival, with no new safety concerns.
Janssen Research & Development.
An additional 5 years of adjuvant aromatase-inhibitor therapy in women with early hormone-receptor–positive breast cancer resulted in longer disease-free survival and a lower incidence of ...contralateral breast cancer than placebo, but not in longer overall survival.
The risk of recurrence of hormone-receptor–positive early breast cancer continues indefinitely.
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Long-term reduction in the risk of recurrence has been achieved with the antiestrogen agent tamoxifen, aromatase inhibitors, or a combination of the two. These treatments are administered in a variety of adjuvant regimens, including tamoxifen for 10 years, tamoxifen for up to 5 years followed by an aromatase inhibitor for 5 years, or an initial aromatase inhibitor for 5 years.
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Extrapolating from these results, many patients have chosen to continue taking an aromatase inhibitor for more than 5 years (if they do not have unacceptable side effects), despite . . .
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