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However, in Era M2, patients achieving EFS24 had similar OS compared to the general population (SMR = 1.35, 95% CI: 0.83-2.09), and lymphoma was no longer the leading cause of death (Figure 1 B&E). Multicohort Study of Conditional Survival and Cause of Death After Achieving Event-Free Survival at 24 Months (EFS24) in Patients With Mantle Cell Lymphoma (MCL) In Era M1, patients achieving EFS24 still had inferior OS compared to the general population (SMR = 2.81, 95% CI: 1.98-3.88), and lymphoma remained the leading cause of death. [Extracted from the article]

Asymmetric Fabry-Perot reflection modulators that use GaAs and InGaAs quantum wells reveal zero phase change when switched, while operating beyond the matching condition. The matching condition is obtained when the effective back mirror reflecting Rbe(-2alphaL) is equal to the front mirror reflecting Rf. Efficient semiconductor spatial light modulators can be based on the above structures.

Deals with a study which analyzed coupled InGaAs quantum-well systems which use filed-induced spatial separation of electron and hole states to modulate the magnitude of exciton optical absorption. Composition of the samples; Function of the effective exciton radius; Benefits from the use of the InGaAs compound.

Investigates three-step asymmetric coupled quantum wells to obtain a higher-degree of negative differential absorption modulation than is obtainable through the quantum-confined Stark effect. Reason for the field-induced enhancement and suppression of electron; Stress-related effects on the electron-light hole; Overview of the Kramers-Kronig relations.

While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). METHODS: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). RESULTS: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E-6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E-6; Pcorrected = 0.01). CONCLUSIONS: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. IMPACT: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study., Other Research Unit

The purpose of this study was to describe a modification of the Massachusetts General Hospital (MMGH) tendon repair and to compare it with three other suture techniques. Twenty human flexor digitorum profundus (FDP) tendons were randomly assigned to the modified Pennington (MP) suture and the MMGH suture. These were compared to the modified Kessler (MK) and Massachusetts General Hospital (MGH) sutures, using data from a previous study. All tendons were repaired with a similar epitendinous stitch and core sutures of 4-0 FiberWire. There was no significant difference in the normalized gliding resistance within the two-strand or four-strand core repair groups. The MP suture had significantly higher 2 mm gap force and ultimate load to failure than the MK suture. The MMGH suture had significantly higher 2 mm gap force and maximum failure ultimate load than the MGH suture. All repairs failed by knot unravelling. [ABSTRACT FROM PUBLISHER]

To describe the behavioral and physiological responses associated with colic, the responses of 20 two-month-old infants with and 20 without colic were studied during a physical examination. Parents kept a diary of infant behaviors (including crying and fussing) for 3 days following the visit. Using Wessel, Cobb, Jackson, Harris, & Detwiler criteria, colic was defined as fussing/crying for 3 hr or more on each of the 3 days. Behavioral data coded by "blind" observers showed that during the physical exam, colic infants cried twice as much, cried more intensely, and were more inconsolable than were control infants. Despite these behavioral differences, heart rate, vagal tone, and cortisol measures indicated no appreciable difference in physiological responsivity for the two groups. At home, parents collected saliva cortisol samples at wakeup, midmorning, midafternoon, and evening for 2 days. In a finding similar to that shown by the laboratory data, the colic and control infants did not have different levels of daily average cortisol. These laboratory and home data provide no evidence of greater responsivity in the physiological substrate of difficult temperament for colic infants and are consistent with evidence of similarity in temperament once colic is resolved. At home, compared with control infants, colic infants did display a blunted rhythm in cortisol production. By diary, they also slept about 2 hr less per day than did control infants. Nighttime sleep was still significantly different when fussing/crying was statistically controlled. These data suggest that colic might be associated with a disruption or delay in the establishment of the circadian rhythm in activity of the hypothalamic-pituitary-adrenocortical axis and associated sleep-wake activity. [ABSTRACT FROM AUTHOR]

PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. RESULTS: Five SNPs were significantly associated (P ≤ 1.0 × 10(-5)) with poorer outcomes in at least one of the four analyses, three of which, rs4910232 (11p15.3), rs2549714 (16q23), and rs6674079 (1q22), were located in long noncoding RNAs (lncRNAs) RP11-179A10.1, RP11-314O13.1, and RP11-284F21.8, respectively (P ≤ 7.1 × 10(-6)). ENCODE ChIP-seq data at 1q22 for normal ovary show evidence of histone modification around RP11-284F21.8, and rs6674079 is perfectly correlated with another SNP within the super-enhancer MEF2D, expression levels of which were reportedly associated with prognosis in another solid tumor. YAP1- and WWTR1 (TAZ)-stimulated gene expression and high-density lipoprotein (HDL)-mediated lipid transport pathways were associated with PFS and OS, respectively, in the cohort who had standard chemotherapy (pGSEA ≤ 6 × 10(-3)). CONCLUSIONS: We have identified SNPs in three lncRNAs that might be important targets for novel EOC therapies., Other Research Unit

Reports on the results of two experiments dealing with behavioral and adrenocortical responses to separation among 9-month-old human infants. Manipulation of the social context of separation; Examination of the effects of group versus singleton care using the less stressful mode of substitute care giving; Infant Distress to Limits temperament; Use of Rothbart's Infant Behavior Questionnaire; Method; Results; Conclusion.

Whilst previous studies have reported that higher body-mass index (BMI) increases a woman’s risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum, and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13,548 cases, 17,913 controls). We combined study-specific adjusted odds ratios (ORs) using a random–effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5kg/m2; 95%CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low grade serous invasive tumours (1.13, 1.03–1.25) and in pre-menopausal women (1.11; 1.04–1.18). Among post–menopausal women, the associations did not differ between HRT users and non–users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

Background: IGF signaling has been implicated in the pathogenesis and progression of ovarian carcinoma (OC). Single agent activity and safety of ganitumab (AMG 479), a fully human monoclonal antibody against IGF1R that blocks binding of IGF1 and IGF2, were evaluated in patients with platinum-sensitive recurrent OC., Methods: Patients with CA125 progression (GCIG criteria) or measurable disease per RECIST following primary platinum-based therapy received 18 mg/kg of ganitumab q3w. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 by an independent radiology review committee (IRC) and/or GCIG CA125 criteria. Secondary endpoints included clinical benefit rate (CBR), progression free survival (PFS) and overall survival (OS)., Results: 61 pts. were accrued. Objective responses were seen in 5/61 patients (ORR 8.2%, 95% CI, 3.1-18.8) with 1 partial response (PR) by RECIST and 2 complete responses (CR) as well as 2 PR by CA125 criteria. CBR was 80.3% (95% CI, 67.8-89.0%). The median PFS according to RECIST by IRC was 2.1 months (95% CI, 2.0-3.1). The median PFS per RECIST IRC and/or CA125 was 2.0 months (95% CI, 1.8-2.2). The median OS was 21 months (95% CI, 19.5-NA). The most common overall adverse events were fatigue (36.1%) and hypertension (34.4%). Grade 1/2 hyperglycemia occurred in 30.4% of patients. Hypertension (11.5%) and hypersensitivity (8.2%) were the most frequent grade 3 adverse events., Conclusions: IGF1R inhibition with ganitumab was well-tolerated, however, our results do not support further study of ganitumab as a single agent in unselected OC patients., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC., Patients and Methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies., Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02-2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to -), 5.4 (4.6-7.0), 3.8 (3.3-4.6), 3.2 (2.9-3.7) and 2.3 (2.1-2.6) years., Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches., Competing Interests: Disclosure BYK served on Invitae Corporation's Advisory Board from 2017 to 2018. IAM has acted on the Advisory Boards for AstraZeneca, Clovis Oncology, Tesaro, Carrick Therapeutics and Takeda. His institution receives funding from AstraZeneca. RG is on the Advisory Boards for AstraZeneca, Tesaro, Clovis and Immunogen and does consultancy work for SOTIO. She has received support to attend conferences from AstraZeneca, Roche and Tesaro. Her institution has received research funding from Boehringer Ingelheim and Lilly/Ignyta and she is the national co-ordinating investigator for the UK for trials sponsored by AstraZeneca and Tesaro and site principal investigator for trials sponsored by AstraZeneca, Tesaro, Immunogen, Pfizer, Lilly and Clovis. PAF has received grants from Novartis, BioNtech and Cepheid as well as personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, TEVA, Astra Zeneca, Merck Sharp & Dohme, Myelo Therapeutics, MacroGenics, Eisai and Puma during the conduct of the study. JDB has acted on Advisory Boards for AstraZeneca and has received support from GSK to attend conferences. His institution receives funding from AstraZeneca and Aprea. UM has shares in Abcodia Ltd. Sandra Orsulic and Beth Y. Karlan have patents on predictive gene signatures in ovarian cancer (US010253368 and EU2908913). All remaining authors have declared no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer., Methods: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype., Results: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant., Conclusions: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

The purpose of this study was to describe a modification of the Massachusetts General Hospital (MMGH) tendon repair and to compare it with three other suture techniques. Twenty human flexor digitorum profundus (FDP) tendons were randomly assigned to the modified Pennington (MP) suture and the MMGH suture. These were compared to the modified Kessler (MK) and Massachusetts General Hospital (MGH) sutures, using data from a previous study. All tendons were repaired with a similar epitendinous stitch and core sutures of 4-0 FiberWire. There was no significant difference in the normalized gliding resistance within the two-strand or four-strand core repair groups. The MP suture had significantly higher 2 mm gap force and ultimate load to failure than the MK suture. The MMGH suture had significantly higher 2 mm gap force and maximum failure ultimate load than the MGH suture. All repairs failed by knot unravelling.

The decrease in responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) system is marked over the first months of life. Seventy-eight healthy infants (44 girls), 7 to 15 weeks old, were given a laboratory mock physical examination. Salivary cortisol samples were collected pre- and postexamination and at home. Behavioral state during the examination and home sleep/wake activity were measured. Subjects younger than 11 weeks showed an increase in pre- to postexamination cortisol, while older subjects did not. Further, there was no decrease in behavioral distress to the examination with age. Infants who showed an early- morning peak (EMP) in home cortisol levels were significantly older and were likely to be those who slept through the night. However, the presence of an EMP was not associated with a lack of cortisol response to the examination. The decrease in cortisol responsiveness witnessed around the age of 3 months is presumably due to other processes associated with age, and not with the expression of the day-night rhythm in basal cortisol.

2,4,5,2',4',5'-hexachlorobiphenyl (HCB) induces hepatic microsomal cytochromes P450 with a similar selectivity for responsive genes to phenobarbital (PB). CYP2Bl, CYP2B2, CYP2C6, CYP3Al, and CYP2Al each showed large strain differences in induction by HCB Fisher F344 >> Wistar Furth (WF) that were much more evident in female rats, paralleling previous observations with PB. These five P450s and epoxide hydrolase were, however, induced more effectively by HCB than by PB and strain differences were even larger. With HCB, strain differences in male rats were much more apparent than with PB. This change was not due to the greater HCB induction since a 2-fold lower induction was maintained even with a 10-fold lower dose of HCB. The sex and strain differences were seen both by immunoblot analysis and by form-selective enzyme activity assays. induction of CYP2B1, CYP2B2, and CYP3A1 by HCB was decreased 3-fold when starvation during the final 24 hr was replaced by continuous feeding. This effect was similar in each strain and therefore independent of the regulatory processes associated with the differential suppression of induction in WF rats. This modulation of induction by feeding was also seen with PB which caused only a 30% lowering of induction in continuously fed F344 rats. A 52-kDa microsomal protein (p52) was prominently induced by both HCB and PB after starvation, while minor induction of a 50-kDa microsomal protein (p50) also occurred after the same treatment. Furthermore, a 100-kDa microsomal protein (p100) was induced by HCB but not by PB and only in rats that were continuously fed. These results suggest that the induction of multiple forms of P450 following HCB treatment functions through the same PB-stimulated pathway that shows a strain-dependent endocrine (GH/T3/testosterone)-sensitive suppression mechanism. The induction of p5O, p52, and plOO by HCB suggests the presence of at least two additional hepatic response mechanisms for HCB.

To investigate the relations among popular measures of neonatal stress and their link to subsequent temperament, 50 full-term newborns from a normal care nursery were examined responding to a heelstick blood draw. Baseline and heelstick measures of behavioral state, heart period, vagal tone, and salivary cortisol were obtained. Recovery measures of behavioral and cardiac activity were also analyzed. Mothers completed Rothbart's Infant Behavior Questionnaire when their infants reached 6 months of age. Baseline vagal tone predicted cortisol in response to the heelstick, suggesting that baseline vagal tone reflects the infants' ability to react to stressors. Greater reactivity to the heelstick (more crying, shorter heart periods, lower vagal tone, and higher cortisol) was associated with lower scores on "Distress-to-Limitations" temperament at 6 months. This finding was consistent with the expectation that the capacity to react strongly to an aversive stimulus would reflect better neurobehavioral organization in the newborn. Recovery measures of cardiac activity approximated and were correlated with baseline measures indicating the strong self-righting properties of the healthy newborn. Finally, vagal tone and salivary cortisol measures were not significantly related, suggesting the importance of assessing both systems in studies of the ontogeny of stress-temperament relations.

3 studies of adrenocortical activity in healthy 9-month-old infants were conducted to examine unanticipated results obtained in previous research. In the first study, morning naps were examined and found to be associated with significant decreases in salivary cortisol. These decreases were followed by a significant return to prenap cortisol concentrations. In the second study, riding for 40 min in the car was also shown to significantly lower salivary cortisol concentrations. This effect was obtained both for infants who did and who did not sleep during the car trip. In the third study, the effect of 30 min of maternal separation in the laboratory on salivary cortisol was compared to the effect of 30 min of play with mother present. Separation resulted in significantly higher salivary cortisol concentrations as compared to play with mother present. In general, correlations between cortisol and behavior were found to be nonsignificant under conditions that did not produce stress elevations in cortisol, while less positive, more distressed behaviour was significantly correlated with cortisol under separation or stress conditions.