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Radiation therapy (RT) refusal is known to have deleterious effects on survival for multiple cancer types. Factors associated with RT refusal by patients with gynecologic malignancies have not been well described. This study aimed to examine factors associated with and the survival impact of documented RT refusal among patients with gynecologic cancers. This study analyzed data from the National Cancer Database (NCDB) of patients with gynecologic cancers diagnosed between 2004 and 2020. Patients were included if they had complete survival data and a documented RT recommendation by their treating physician in the NCDB. Patients coded as received RT were compared with those coded as refused RT in the NCDB using a multivariate log binomial regression with robust variance to yield incidence rate ratios (IRR). Overall survival was analyzed using a multivariate (MV) Cox proportional hazards model to yield hazard ratios. This study identified 209,976 patients. A total of 5.75% (n = 12,081) patients were coded as refusing RT. Multivariable IRR showed that documentation of RT refusal was positively associated with older age (MV IRR, 1.04; 95% CI, 1.041-1.045), Native Hawaiian Pacific Islander race (1.72 [1.27-2.32]), and increased morbidity (score = 1: 1.06 [1.02-1.11]; score = 2: 1.20 [1.12-1.29]; score ≥3: 1.26 [1.14-1.38]). Negative associations were seen with Hispanic ethnicity (0.74 [0.67-0.80]), having insurance (0.58 [0.53-0.63]), and annual income >$74,063 (0.85 [0.81-0.90]). During the 16-year period, a statistically significant test for trend (P =.001) for increasing RT refusal was noted. RT refusal was associated with a significantly higher risk of death (MV hazard ratio, 1.59 [1.55-1.63]). For patients with gynecologic malignancies diagnosed from 2004 to 2020, an increase in documented RT refusal is associated with decreased overall survival in all disease types. Targeted interventions aimed at mitigating potential sociodemographic barriers to receipt of RT are warranted. [ABSTRACT FROM AUTHOR]

This study examines advertising of top-selling voice-activated smart speakers in the United States to understand how advertisers are promoting these devices to consumers. The study identifies four representations of technology in smart speaker advertising. This includes technology as human, technology as self-expression and happiness, technology as progress, and technology as productivity. Engaging in semiotic analysis of select advertising, the study reveals deeper meaning, ideology, and myths in smart speaker advertising. Implications for culture and consumption are discussed. [ABSTRACT FROM AUTHOR]

Background: Emergency contraception (EC) efficacy is dependent on timing of administration. Adequate pharmacy stock information and accurate patient counseling are important to ensure timely access. Objective: This study evaluates pharmacist reported availability and counseling for levonorgestrel (LNG) and ulipristal acetate (UPA), and identifies differences between caller type and pharmacies in metropolitan vs nonmetropolitan areas of Georgia. Methods: This prospective, randomized, telephone-based study included 25% of Georgia community pharmacies, stratified by geographic location. Calls were made by investigators, first posing as a mystery shopper inquiring about EC stock and efficacy, then 3–6 weeks later as a researcher inquiring about EC stock. Analysis utilized descriptive statistics, chi Square, and logistic regression. Results: Of 600 pharmacies, the mystery shopper caller reached 86%: 74% of pharmacists initially discussed LNG, 57.1% had it stocked, more often in metropolitan areas (OR 1.7, 95% CI 1.08–2.6). Ulipristal acetate was discussed by 1.9% and reported in-stock < 1%. Of those who discussed window of efficacy, 79% indicated LNG would either not work 4 days after intercourse or they were unsure. The research caller successfully completed a second call for 64% of pharmacies: 57% stocked LNG, 3% stocked UPA, and UPA was more likely to be stocked in metropolitan pharmacies. Conclusion: In Georgia, UPA availability is poor, and nonmetropolitan pharmacies were less likely to stock LNG and UPA. A minority of pharmacists correctly indicated that LNG may work up to 120 hours after intercourse. Strategies are needed to overcome barriers to EC availability in community pharmacies and support pharmacists' EC counseling. [ABSTRACT FROM AUTHOR]

Rights-based theories of private law tend to be wrongs based and defendant focused. But many private law wrongs do not seem like genuine wrongs, at least when the background distribution of resources is unjust. A very poor person, for example, may be held legally liable for breaching a one-sided contract with a very rich person. When such a contract reflects and reproduces existing injustice, it is hard to view the poor person's breach of such a contract as a genuine wrong against the rich person. Conversely, some obvious moral wrongs do not generate legal liability. There is, for example, no private law duty of rescue in the absence of a prior relationship in many situations in which most would agree that there is a moral duty of rescue. Thus, private legal liability seems not to track moral wrongdoing in significant respects, raising the question what instead justifies such liability. Instead of justifying private liability in terms of the defendant's wrongdoing, as corrective justice and civil recourse theorists do, we should seek a justification in terms of the plaintiff's moral permission to enforce her apparent rights. Switching our gaze from the defendant's wrongdoing to the plaintiff's moral permission to enforce her rights will not be normatively consequential if the plaintiff's moral permission arises when and only when the defendant has wronged her. But, I argue, background injustice can drive a wedge between genuine wrongdoing and the plaintiff's moral permission. Thus, by reconceptualizing private liability in terms of a plaintiff's moral permission to enforce her apparent rights, private law may be justified by the essential role it plays in constituting non-ideal political morality. [ABSTRACT FROM AUTHOR]

Under the Atmospheric River Reconnaissance (AR Recon) Program, ocean drifting buoys (drifters) that provide surface pressure observations were deployed in the northeastern Pacific Ocean to improve forecasts of U.S. West Coast high-impact weather. We examine the impacts of both AR Recon and non-AR Recon drifter observations in the U.S. Navy's global atmospheric data assimilation (DA) and forecast system using data-denial experiments and forecast sensitivity observation impact (FSOI) analysis, which estimates the impact of each observation on the 24-h global forecast error total energy. Considering all drifters in the eastern North Pacific for the 2020 AR Recon season, FSOI indicates that most of the beneficial impacts come from observations in the lowest quartile of observed surface pressure values, particularly those taken late in the DA window. Observations in the upper quartile have near-neutral impacts on average and are slightly nonbeneficial when taken late in the DA window. This may occur because the DA configuration used here does not account for model biases, and innovation statistics show that the forecast model has a low pressure bias at high pressures. Case studies and other analyses indicate large beneficial impacts coming from observations in regions with large surface pressure gradients and integrated vapor transport, such as fronts and ARs. Data-denial experiments indicate that the assimilation of AR Recon drifter observations results in a better-constrained analysis at nearby non-AR Recon drifter locations and counteracts the NAVGEM pressure bias. Assimilating the AR Recon drifter observations improves 72- and 96-h Northern Hemisphere forecasts of winds in the lower and middle troposphere, and geopotential height in the lower, middle, and upper troposphere. Significance Statement: The purpose of this study is to understand how observations of atmospheric pressure at the ocean surface provided by drifting buoys impact weather forecasts. Some of these drifting buoys were deployed under a program to study atmospheric rivers (ARs) to improve forecasts of high-impact weather on the West Coast. We find that these observations are most effective at reducing forecast errors when taken in regions near fronts and cyclones. The additional drifting buoys deployed under the AR Reconnaissance project reduce forecast errors at 72 and 96 h over North America and the Northern Hemisphere. These results are important because they illustrate the potential for improving forecasts by increasing the number of drifting buoy surface pressure observations over the world oceans. [ABSTRACT FROM AUTHOR]

Policies implemented to control the COVID-19 (C19) pandemic have faced public resistance. We examined this issue via an experimental vignette study embedded in a May 2020 national (U.S.) survey conducted by YouGov. Specifically, we explore how the public perceived a local policymaker proposing a C19-related isolation policy, based on the policy's invasiveness or its punitivity. We find that more intrusive and more punitive policies generally resulted in colder feelings towards, and harsher perceptions of, the policymaker. However, our results suggest that the main driver of public sentiment towards the policymaker was the invasiveness of the proposed policy, with the policy's punitivity being less impactful. We discuss these findings in relation to policymaking, policy support and compliance, and tradeoffs between informal/formal controls, and intrusive/punitive policies. [ABSTRACT FROM AUTHOR]

Children's tendency to eat while they are emotional, irrespective of satiety, is termed emotional eating (EE). EE develops early in childhood and has been associated with maternal modelling of EE and food parenting practices. In addition, individual differences in a child's appetitive traits (ie, food approach behaviors) are related to the development of EE. The objective of this study was to examine whether or not the previously identified mediating relationship between maternal EE and child EE via maternal use of food as a reward, food for emotion regulation, or restriction of food for health reasons varies as a function of child food approach. A cross-sectional online questionnaire study was conducted. One hundred eighty-five mothers of children aged between 3 and 5 years were recruited between January 2020 and March 2020 from advertisements placed on social media in the United Kingdom. Questionnaires assessed child EE, child food approach tendencies, maternal EE, and food parenting practices. Using PROCESS version 3.4, model 14, moderated mediations were employed to assess whether or not child food approach tendencies moderated the mediating effect of controlling food parenting practices between maternal EE and child EE. This study found the relationship between maternal reports of maternal EE and child EE was mediated by maternal use of food as a reward, but only for children with high food approach tendencies (B =.05, 95% CI 0.010 to 0.101; R 2 = 48%). This study also found the relationship between maternal EE and child EE was mediated by maternal use of restriction for health reasons, but only when children showed medium (B =.02, 95% CI 0.004 to 0.072) to high (B =.06, 95% CI 0.016 to 0.110; R 2 = 51%) food approach tendencies. The potential for the intergenerational transmission of EE via the use of food as a reward and food restriction may be exacerbated when a child has higher food approach behaviors. [ABSTRACT FROM AUTHOR]

Emotional eating (EE) is defined as eating in response to negative emotions (e.g., sadness and boredom). Child temperament and parental feeding practices are predictive of child EE and may interact to shape child EE. Previous research has demonstrated that children eat more when they are experiencing sadness, however, boredom-EE (despite how common boredom is in children) has yet to be explored experimentally using remote methodologies. The current study explores whether feeding practices and child temperament interact with mood to predict children's snack selection in an online hypothetical food choice task. Using online experimental methods, children aged 6-9-years (N = 347) were randomised to watch a mood-inducing video clip (control, sadness, or boredom). Children completed a hypothetical food choice task from images of four snacks in varying portion sizes. The kilocalories in children's online snack choices were measured. Parents reported their feeding practices and child's temperament. Results indicated that the online paradigm successfully induced feelings of boredom and sadness, but these induced feelings of boredom and sadness did not significantly shape children's online food selection. Parental reports of use of restriction for health reasons (F = 8.64, p =.004, n2 = 0.25) and children's negative emotionality (F = 6.81, p =.009, n2 = 0.020) were significantly related to greater total kilocalorie selection by children. Three-way ANCOVAs found no evidence of any three-way interactions between temperament, feeding practices, and mood in predicting children's online snack food selection. These findings suggest that children's hypothetical snack food selection may be shaped by non-responsive feeding practices and child temperament. This study's findings also highlight different methods that can be successfully used to stimulate emotional experiences in children by using novel online paradigms, and also discusses the challenges around using online methods to measure children's intended food choice. [ABSTRACT FROM AUTHOR]

Lower income households are at greater risk of food insecurity and poor diet quality than higher income households. In high-income countries, food insecurity is associated with high levels of obesity, and in the UK specifically, the cost of living crisis (i.e., where the cost of everyday essentials has increased quicker than wages) is likely to have exacerbated existing dietary inequalities. There is currently a lack of understanding of the impact of the current UK cost of living crisis on food purchasing and food preparation practices of people living with obesity (PLWO) and food insecurity, however this knowledge is critical in order to develop effective prevention and treatment approaches to reducing dietary inequalities. Using an online survey (N = 583) of adults residing in England or Scotland with a body mass index (BMI) of ≥30 kg/m2, participants self-reported on food insecurity, diet quality, perceived impact of the cost of living crisis, and their responses to this in terms of food purchasing behaviours and food preparation practices. Regression analyses found that participants adversely impacted by the cost of living crisis reported experiencing food insecurity. Additionally, food insecurity was associated with use of specific purchasing behaviours (i.e., use of budgeting, use of supermarket offers) and food preparation practices (i.e., use of energy-saving appliances, use of resourcefulness). Exploratory analyses indicated that participants adversely impacted by the cost of living crisis and who used budgeting had low diet quality, whereas use of meal planning was associated with high diet quality. These findings highlight the fragility of food budgets and the coping strategies used by PLWO and food insecurity during the cost of living crisis. Policy measures and interventions are urgently needed that address the underlying economic factors contributing to food insecurity, to improve access to and affordability of healthier foods for all. [ABSTRACT FROM AUTHOR]

Emotional eating (EE; defined as overeating irrespective of satiety and in response to emotional states) develops within childhood, persists into adulthood, and is linked with obesity. The origins of EE remain unclear, but parental behaviours (e.g., controlling feeding practices and modelling) and child characteristics (e.g., temperament) are often implicated. To date, the interaction between these influences has not been well investigated. This study explores whether the relationship between parent and child EE is shaped by parental feeding practices, and if the magnitude of this relationship varies as a function of child temperament. Mothers (N = 244) of 3–5‐year‐olds completed questionnaires about their EE, feeding practices, their children's EE and temperament. Results showed that parental use of food to regulate children's emotions fully mediated the relationship between parent and child EE, and using food as a reward and restricting food for health reasons partially mediated this relationship. Analyses demonstrated that the mediated relationship between parent and child EE via use of food as a reward and restriction of food for health reasons varied as a function of child negative affect, where high child negative affect moderated these mediations. These findings suggest child EE may result from interrelationships between greater parent EE, use of food as a reward, restriction of food for health reasons and negative affective temperaments, but that greater use of food for emotion regulation may predict greater child EE irrespective of child temperament. Key messages: Child temperament moderates the significant mediating relationships between parent EE, certain parental feeding practices and child EE.Parental use of food as a reward significantly mediates the relationship between parent and child EE only for children who are medium or high in negative affect.Parental restriction of food for health reasons significantly mediates the relationship between parent and child EE only for children who are high in negative affect.In children who are low in negative affect, parental rewarding and restrictive feeding practices do not mediate the relationships between parent and child EE.Models of eating behaviour should consider how child characteristics can shape the expression and influence of behaviours that are known to place children at greater risk of obesogenic eating behaviours. [ABSTRACT FROM AUTHOR]

To investigate whether earlier "post-term" monitoring of South Asian (SA) pregnancies from 39 weeks' gestation with amniotic fluid index (AFI) and cardiotocography (CTG) detected suspected fetal compromise. Retrospective cohort study of all SA-born women at an Australian health service with uncomplicated, singleton pregnancies following the introduction of twice-weekly AFI and CTG monitoring from 39 weeks. Monitoring results, and their association with a perinatal compromise composite (including assisted delivery for fetal compromise, stillbirth, and NICU admission) were determined. 771 SA-born women had earlier monitoring, triggering delivery in 82 (10.6%). 31 (4%) had a non-reassuring antepartum CTG (abnormal fetal heart rate or variability, or decelerations) and 21 (2.7%) had an abnormal AFI (≤ 5 cm). Women with abnormal monitoring were 53% (95% CI 1.2–1.9) more likely to experience perinatal compromise and 83% (95% CI 1.2–2.9) more likely to experience intrapartum compromise than women with normal monitoring. Monitoring from 39 weeks identified possible fetal compromise earlier than it otherwise would have been, and triggered intervention in 10% of women. Without robust evidence to guide timing of birth in SA-born women to reduce rates of stillbirth, earlier monitoring provides an alternative to routine induction of labour. [ABSTRACT FROM AUTHOR]

Research Summary: Using a national survey experiment, we examined Americans' national and local‐level support for facilities that provide a safer space for individuals to consume illicit drugs under the supervision of medical professionals. We determined whether support levels differed based on (1) the label used to refer to such facilities ("safe injection facilities" vs. "overdose prevention sites"), (2) whether beneficial information is provided about these facilities regarding either a crime control framework or a public health framework, or not. We also considered how national support differed from local‐level support, and how national or local‐level perceptions of the opioid epidemic influenced support. Policy Implications: We found that the label used to refer to these facilities was the most important factor influencing support levels. The public was also much more supportive of these facilities at the national level than at the local level, which suggests that support for these facilities is impacted by "Not In My Backyard" (NIMBY) concerns. Perceptions of an opioid epidemic either nationally or locally also influenced support levels. The major policy takeaways are that (1) proponents of these facilities should refer to them using labels that highlight overdose prevention ("overdose prevention site"), rather than safe drug use ("safe injection facility") and (2) discussions about local facilities should be placed in the context of both the national and local opioid epidemic to help mitigate NIMBY concerns. [ABSTRACT FROM AUTHOR]

• Boredom was induced in children aged 4–5-years using a novel laboratory paradigm. • Children ate more kilocalories when feeling bored compared to a control condition. • Non-responsive feeding & negative affect interact to predict boredom emotional eating. Children who emotionally eat (EE) tend to consume palatable foods that are high in sugar and fat. How EE develops remains unclear, but children's temperament and parental feeding practices may interact to shape child EE. To date, no research has explored these interaction effects on EE experimentally. Furthermore, most research has explored EE in response to generic 'negative' mood rather than specific negative emotions, such as boredom, which has never been explored in this context. This study aimed to explore interactions between induced mood condition (sadness, boredom, control), parent-reported non-responsive feeding practices and parent-reported child temperament (negative affect, surgency, effortful control) in predicting kilocalories consumed by children aged 4–5-years in a laboratory setting. Using three-way ANOVA, the interactions between mood state, parental feeding practice and child temperament were assessed. Results indicated that children who experienced boredom consumed significantly more total kilocalories than children in the control condition. Additionally, children with high negative affect who also had parents who reported high use of food for emotion regulation consumed significantly more kilocalories from sweet food when experiencing boredom compared to control condition, and children with high negative affect who also had parents who reported low use of food as a reward consumed significantly more kilocalories from sweet food when experiencing boredom compared to control condition. These findings suggest that feelings of boredom differentially predict children's snack food intake, and that child negative affect and non-responsive feeding practices play an important role in the expression of this relationship. [ABSTRACT FROM AUTHOR]

Warming oceans are causing changes in the distribution of numerous species. If greenhouse gas production continues to follow current trends, further distribution changes will result. It is often assumed that range shifts into higher latitudes may mitigate threats to susceptible species. Sabellaria alveolata is an important intertidal ecosystem engineer and protected by the UK Biodiversity Action Plan. In this study we created a habitat suitability model for S. alveolata around Great Britain and quantified changes in coastal suitability with increasing sea surface temperatures (SST) using Representative Concentration Pathway (RCP) scenarios modelled by the International Panel on Climate Change. The model included maximum and minimum SST, substrate, slope, kinetic energy due to waves and currents, photosynthetically active radiation, and the coefficient of light attenuation. The model performed very well (AUC = 0.932, 50.2% of deviance explained) and all variables explaining comparable deviance (up to 10%). Recent SST was then combined with predicted SST increases, leading to suitable habitat locations expanding across the southern and western GB coastlines and resulting in larger patches, hence potential for connectivity. Some northern extension was observed; however, this was limited and patchy. The greatest extensions were seen on the south coast, with most of the south coast becoming a continuous network with excellent suitability. With an increase of 1.2 °C, the extent of coast in the excellent suitability class was increased by 5.75% compared to 2020, and by 38.1% with 3.2 °C. Despite the importance of winter temperature in driving S. alveolata distribution, over-riding environmental constraints prevented any major northward migration. The assertion that potential for range shifts to higher latitudes may mitigate the effects of climate change depends on niche availability which may not always be realised. • Sabellaria alveolata is a bioengineer, likely to be impacted by climate change. • We developed a GB wide habitat suitability model for S alveolata. • After substrate, coefficient of light attenuation was the most influential variable. • Warming oceans increased overall suitability of GB coast to S. alveolata. • This demonstrates a sensitivity of sessile marine species to climate change. [ABSTRACT FROM AUTHOR]

This systematic review evaluates the efficacy of intravaginal diazepam in treating chronic pelvic pain and sexual dysfunction associated with high‐tone pelvic floor dysfunction. A literature search was conducted in Medline and Web of Science, including articles from the database's inception to July 2019. The search identified 126 articles, and 5 articles met study inclusion criteria: 2 observational reviews and 3 small randomized, controlled trials (RCTs) evaluating intravaginal diazepam for high‐tone pelvic floor dysfunction. The 2 observational studies identified subjective reports of improvement in sexual function for a majority of women, 96% and 71%, in each study. However, there were no statistical differences between Female Sexual Function Index (FSFI) and Visual Analog Scale (VAS) scores for pain identified. One RCT found no significant changes between groups in median FSFI or VAS scores, and a second RCT found no significant changes between groups in 100‐mm VAS scores. The third RCT demonstrated that compared with placebo, treatment with transcutaneous electrical nerve stimulation and intravaginal diazepam for women with vestibulodynia and high‐tone pelvic floor dysfunction yielded significant differences in reduction of dyspareunia (P ≤.05), ability to relax pelvic floor muscles after contraction (P ≤.05), and current perception threshold values at a 5‐Hz stimulation related to C fibers (P <.05), but no significant changes in 10‐cm VAS scores. Intravaginal diazepam may be helpful in women with a specific diagnosis of high‐tone pelvic floor dysfunction, but more and larger studies are needed to confirm these potential effects. [ABSTRACT FROM AUTHOR]

Maternal opioid use disorder increased > 4‐fold from 1999 to 2014 and is associated with poor maternal and fetal outcomes. Women with opioid use disorder are at 2 to 3 times greater risk for unintended pregnancy than the general population and may face additional barriers to accessing and effectively using contraception compared to women without opioid use disorder, particularly highly effective long‐acting reversible contraception. Additionally, women with opioid use disorder tend to use less effective forms of contraception such as condoms alone. Barriers to contraceptive access include patient misconceptions or knowledge gaps regarding reproductive health and family planning, cost, intimate partner violence, fear of criminalization, difficulty accessing care, comorbid health conditions, and health care provider misconceptions or practice limitations. Strategies that may assist women with opioid use disorder in achieving their family planning goals include colocation of family planning services within opioid treatment facilities, optimization of patient care services to minimize the need for costly and/or time consuming follow‐up, increasing provider education and awareness of best practices in family planning and opioid use disorder treatment, and providing patient‐centered family planning education and counseling. Additional research is needed to identify and develop strategies that empower women who use opioids to effectively access and use their preferred contraceptive method. [ABSTRACT FROM AUTHOR]

This Viewpoint explains the use of opportunistic salpingectomy, removal of the fallopian tubes for the primary prevention of ovarian cancer in a woman already undergoing pelvic surgery for another indication. [ABSTRACT FROM AUTHOR]

According to narrative identity theory, to desist from breaking the law, offenders must fashion a prosocial identity through a process of redemption by "making good" of past negative events. To improve understanding of women offenders' redemption, analyses were conducted of the life stories and the identity change those stories revealed for 118 U.S. women with histories of multiple criminal convictions. Women most often described redemption from illegal activity and substance misuse, distress and trauma, and the challenges of giving birth and parenting. They rarely described redemption in educational and employment settings. The numbers and types of accounts of redemption did not explain desistance. However, qualitative analyses showed important differences in the redemption accounts of women who did and did not desist. Persisters' stories of redemption tended to lack coherence and revealed tendencies to minimize both the negative effects of illegal behavior and the connection of illegal behavior to identities. Desisters' accounts emphasized women's strong motivations to change and their efforts to distance their current from their prior selves, steer internal change, and identify valuable prosocial qualities in themselves. Promising treatment interventions include support for women's development of coherent life stories and autonomy support to increase motivation to change. Findings also suggest the need for policy change to increase both employment opportunities for women offenders and programs that provide employment and education that promote prosocial identity development. [ABSTRACT FROM AUTHOR]

Atmospheric rivers, often associated with impactful weather along the west coast of North America, can be a challenge to forecast even on short time scales. This is attributed, at least in part, to the scarcity of eastern Pacific in situ observations. We examine the impact of assimilating dropsonde observations collected during the Atmospheric River (AR) Reconnaissance 2018 field program on the Navy Global Environmental Model (NAVGEM) analyses and forecasts. We compare NAVGEM's representation of the ARs to the observations, and examine whether the observation–background difference statistics are similar to the observation error variance specified in the data assimilation system. Forecast sensitivity observation impact is determined for each dropsonde variable, and compared to the impacts of the North American radiosonde network. We find that the reconnaissance soundings have significant beneficial impact, with per observation impact more than double that of the North American radiosonde network. Temperature and wind observations have larger total and per observation impact than moisture observations. In our experiment, the 24-h global forecast error reduction from the reconnaissance soundings can be comparable to the reduction from the North American radiosonde network for the field program dates that include at least two flights. [ABSTRACT FROM AUTHOR]

To systematically review the literature around the safety and effectiveness of hormonal contraception for women who use opioids. Our specific research questions are: 1) Among women who use opioids, do those who use hormonal contraception have increased adverse health events compared with those who do not use hormonal contraception? 2) Are there drug interactions between hormonal contraception and opioids that cause decreased effectiveness or increased toxicity from either drug? We searched Medline, Embase, PsychInfo, CINAHL, the Cochrane Library, and clinicaltrials.gov through August 2018. We considered randomized controlled trials, cohort studies, and case-control studies, as well as pharmacokinetic and pharmacodynamic studies. We planned to use standard frameworks to assess risk of bias of included studies. The search identified 1852 articles. The full text of 66 articles was reviewed, and none met inclusion criteria. Because we found no direct evidence on the safety and effectiveness of hormonal contraception for women who use opioids, we considered theoretical concerns. While women with OUD have a high prevalence of co-morbidities, such as viral hepatitis, generally women with medical conditions can safely use most contraceptive methods. When considering the pharmacokinetics and pharmacodynamics of hormonal contraception and opioids, there is little theoretical concern for interactions. Therefore, future research efforts could focus on improving access to the full range of contraceptive methods for women who use opioids, reducing unnecessary barriers to initiating and using contraception, while ensuring voluntary choice related to contraceptive use. [ABSTRACT FROM AUTHOR]

To report the first described case of robotic-assisted utero-ovarian transposition followed by anatomic repositioning in the pelvis and cervicovaginal anastomosis in a woman with uterine fibroids, which was performed for fertility preservation in the context of pelvic radiation for rectal cancer. Description of technique and live-action narrated surgical footage showing uterine transposition and repositioning. University hospital. A 36-year-old woman with a new diagnosis of cT3N2M0 rectal adenocarcinoma planned for neoadjuvant chemotherapy and pelvic radiation and desired fertility preservation permissive of future pregnancy. A transvaginal ultrasound revealed a 5-cm posterior leiomyoma and a normal endometrial cavity. The patient elected for utero-ovarian transposition before chemoradiation. The patient included in this video gave consent for publication and posting of the video online, including on social media, the journal website, scientific literature websites, and other applicable sites. Per institutional guidelines, an Institutional Review Board review was not required. Robotic-assisted utero-ovarian transposition was performed in an inpatient setting 2 weeks after ovarian stimulation and oocyte retrieval. She was given a gonadotropin-releasing hormone agonist for menstrual suppression after oocyte retrieval. The uterus and adnexa were transposed en bloc to the upper abdomen, with perfusion via retroflected infundibulopelvic ligaments. Intravenous indocyanine green was administered intraoperatively to visualize uterine perfusion. Three weeks postoperatively, the patient underwent surgical management of small bowel obstruction, which was successfully managed with laparoscopic adhesiolysis. The patient subsequently completed chemoradiation and had a complete response to the rectal tumor. She therefore elected for surveillance. Seven months after transposition and 2 months after completion of treatment, the patient underwent uncomplicated robotic-assisted utero-ovarian anatomic repositioning in the pelvis with cervicovaginal anastomosis. Chromopertubation confirmed tubal patency. Restoration of normal pelvic anatomy and resumption of reproductive physiology. At her 4-month postoperative visit, the cervix and vagina were normal in appearance. The patient reported the return of spontaneous menses and sexual activity without complications. This case is unique because of the presence of bulky intramural uterine fibroids. The described technique may be useful for selected cancer patients who desire to carry a pregnancy after pelvic radiation for cancer treatment, and demonstrates that patients considering utero-ovarian transposition need not be excluded solely on the basis of the presence of uterine fibroids. [ABSTRACT FROM AUTHOR]

Besides their function in limiting blood loss and promoting wound healing, experimental evidence has highlighted platelets as active players in all steps of tumorigenesis including tumor growth, tumor cell extravasation, and metastasis. Additionally, thrombocytosis in cancer patients is associated with adverse patient survival. Due to the secretion of large amounts of microparticles and exosomes, platelets are well positioned to coordinate both local and distant tumor-host crosstalk. Here, we present a review of recent discoveries in the field of platelet biology and the role of platelets in cancer progression as well as challenges in targeting platelets for cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: Depth of myometrial invasion is an important determinant for performing lymphadenectomy to remove endometrial cancer. Frozen section of the uterus correlates with final pathology 87%-92% of the time but is associated with increased time and expense. The current study investigated the effectiveness of a technique we developed to use in the operating room immediately after the uterus is removed. The research was conducted to determine if the technique could be used to predict the depth of invasion accurately, compared to use of frozen section. Materials and Methods: Fifteen women with endometrial cancer, who were undergoing hysterectomy and bilateral salpingo-oophorectomy with possible lymphadenectomy, were recruited for this study. Each patient was injected intravenously with fluorescein dye prior to ligating the uterine arteries. The hysterectomy specimen was taken to the pathology department, bivalved, and the most suspicious areas were excised as a transverse section incorporating the endometrium and myometrium. Under ultraviolet light a measurement of the tumor (nonfluorescent) compared with the full thickness was taken. Identical specimens were subjected to frozen section of the same area, and these values were compared with the final pathology results. Pearson's correlation coefficient was used to compare results between the groups. Results: The correlation between depth of invasion predicted by fluorescein and final pathology was high, with an r value of 0.8765 ( p < 0.05) and was comparable to the frozen-section correlation with final pathology results ( r = 0.8707 [ p < 0.05]). When patients' specimens were categorized as either <50% or >50% invasion, χ2 analysis revealed fluorescein to be significantly predictive of final pathology results ( p = 0.01). Conclusions: These results suggest that a rapid and inexpensive test in the operating room can help determine which patients require lymphadenectomy for invasive endometrial cancer. (J GYNECOL SURG 34:84) [ABSTRACT FROM AUTHOR]

Objective A commercial formulation of injectable 17α-hydroxyprogesterone (17OHP) for prevention of preterm birth was introduced in 2011; however, use of compounded formulations remains widespread. This study compared the frequency of adverse drug reactions (ADRs) associated with compounded versus commercial 17OHP formulations, aiding in provider assessment of 17OHP tolerability. Study Design A retrospective cohort evaluation of data obtained from the electronic medical record (EMR) of patients prescribed weekly 17OHP injections at an obstetric clinic between 2009 and 2015 was performed. A descriptive analysis characterized the frequency and proportion of ADRs associated with 17OHP administration. Patient differences between 17OHP formulations were identified with t-test, chi-square, or Fischer's exact tests. Results Of 175 patients included, 56% received commercial formulation and 44% received compounded formulation. ADRs occurred in 16 patients, all of whom received the compounded formulation (p < 0.001). The most common ADRs were injection site reaction (n = 7) and acute coughing following 17OHP administration (n = 6). Of patients with an ADR, 63% discontinued all medication therapy for prevention of preterm birth or changed to an alternative therapy. Conclusion Comparison of ADR rates between compounded and commercial formulation differed significantly. In addition to food and drug administration (FDA) compliance, providers may consider preferential use of the commercial formulation, since 21% of women receiving compounded product experienced an ADR. [ABSTRACT FROM AUTHOR]

At both UK and global level, dietary consumption patterns need to change to address environmental, health and inequality challenges. Despite considerable policy interventions, the prevalence of overweight and obesity in the United Kingdom has continued to rise with obesity now a leading cause of mortality and morbidity. Obesity prevalence is greater among those on lower incomes and the current UK food system, including government policy, does not effectively address this. Current behavioural approaches, without the support of structural changes in the system, may even widen the inequalities gap. Hence, using behavioural insights from those living with obesity and food insecurity, the project will explore potential avenues that can be applied in the food system to promote healthier choices in the food retail environment. The National Food Strategy report recommends that the UK food system should ensure "safe, healthy, affordable food; regardless of where people live or how much they earn". However, the association between food insecurity and the development of obesity is not well understood in relation to purchasing behaviours in the UK retail food environment, nor is the potential effectiveness of interventions that seek to prevent and reduce the impact of diet‐induced health harms. The FIO Food (Food insecurity in people living with obesity – improving sustainable and healthier food choices in the retail food environment) project provides a novel and multi‐disciplinary collaborative approach with co‐development at the heart to address these challenges. Using four interlinked work packages, the FIO Food project will combine our knowledge of large‐scale population data with an understanding of lived experiences of food shopping for people living with obesity and food insecurity, to develop solutions to support more sustainable and healthier food choices in the UK retail food environment. [ABSTRACT FROM AUTHOR]

Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma. Because of aggressive tumor biology and relative chemotherapy and radiotherapy resistance, efficacious therapies to achieve prolonged survival or cure in those with both early and advanced-stage uterine leiomyosarcoma have been elusive. The strongest determinant of survival remains stage at diagnosis, though prediction models may provide a more accurate prognosis. Given the aggressive nature of this sarcoma subtype, novel early detection strategies and targeted therapies are the focus of several recently published and ongoing studies. While gemcitabine/docetaxel and doxorubicin remain the most active regimens in the treatment of advanced or recurrent disease, currently available cytotoxic regimens remain inadequate, with 5-year disease-specific survival of < 30%. Pazopanib, trabectedin and olaratumab, are FDA-approved, targeted therapies with activity in uterine and other leiomyosarcomas, while aromatase inhibitors and immunotherapies are under active investigation. This review provides a critical appraisal of the literature regarding the contemporary surgical and medical management of uterine leiomyosarcoma, the role of targeted therapies, and the implications of uterine morcellation on gynecologic surgical practice. [ABSTRACT FROM AUTHOR]

Economic analysis of law has traditionally assumed that legal rules are or ought to be designed to maximize social welfare taking as given that legal subjects are like Holmes's "bad man"--rational, self-interested agents who care about complying with the law only insofar as noncompliance exposes them to the risk of sanctions. But while it is plausible to suppose that some legal subjects are, like Holmes's bad man, "externalizers" of legal rules, it is likely that others regard the law from the "internal point of view"--that is, they are "internalizers" of legal rules who are motivated to conform to legal rules regardless of the consequences of defiance. In this Article, I ask what specific doctrinal implications for contract law follow when we assume that there are both internalizers and externalizers in the subject population while keeping the standard economic framework otherwise intact. I analyze several contract law phenomena: the expectation principle, according to which a victim of a breach of contract is entitled to her expectation, and no more than her expectation; the penalty doctrine and stipulated damages clauses; the doctrine of willful breach; and the doctrine of contract modification. The resulting analysis shows that internalizers respond to these doctrines differently from externalizers such that the prescriptive implications of economic analysis for the design of contract law doctrines may change once we recognize that there are both internalizers and externalizers in the subject population. For example, the presence of internalizers in the subject population provides a justification for punishing some "willful breaches" more harshly than ordinary breaches. It also helps to justify the modern doctrine of contract modification. [ABSTRACT FROM AUTHOR]

Consequentialist analysts of legal rules tend to focus their attention on Holmes’s “bad man, ” who conforms to legal rules only out of fear of legal sanctions. On this view, legal rules should be designed to give self-interested legal subjects sufficient reason to choose socially optimal actions. But many people conform to legal rules simply because they are the rules, even when their self-interest dictates doing otherwise. At first glance, this focus on the bad man seems to make sense. Lawmakers, it is plausible to suppose, don’t have to worry about the “good man ” when designing legal rules because he will do what they want him to do anyway by conforming to the law. In other words, good man analysis of law is simple and so can be safely ignored. But good man analysis of law is much more complex than scholars have previously supposed, and ignoring the good man will therefore lead consequentialist lawmakers to err. People are motivated to comply with legal rules for various different kinds of reasons, and this variety matters for their behavior by affecting both their short-run responses to legal rules and their long-run attitudes towards the law. A lawmaker ought to design legal rules in a way that attends to this variety if her aim is to design socially optimal rules. This Article systematically analyzes the problem of legal design in the face of the diversity of motivational types that exist in the population of legal subjects. Part I develops a typology of good persons by exploring the causes and consequences of legal norm internalization— the ways in which a person’s preferences are transformed such that he comes to value complying with legal rides for the sake of the rules. Part II argues that a good person’s type matters for his behavior in a number of important ways. For example, it affects the way in which he chooses among actions that conform to legal norms and the ways in which he responds to the various kinds of uncertainty to which the legal system exposes him. Part III derives normative implications of my analysis for consequentialist lawmakers, while also addressing the converse worry that good man analysis of law is too complex to be tractable. The overall aim is to systematically examine the ways in which a diversity of motivations in the population complicates the problem of legal design for legislators, judges, and administrative officials, and to develop an organizing framework that can be used to think about the problem rigorously, which I illustrate by exploring some examples. [ABSTRACT FROM AUTHOR]

Recent research has examined the role of the narrative construction of identity in desistance from criminal offending and substance use. The narrative identity theory of desistance was developed with a population of male offenders. The present analysis explores the applicability of the theory to a sample of substance-using pregnant women and mothers, a highly stigmatized and increasingly criminalized group. The analysis of in-depth interview data reveals that desisting women constructed narrative identities that emphasized their moral agency and resisted the stigmatizing discourse surrounding substance-using mothers. The results support the narrative identity theory of desistance by demonstrating its applicability to a population for which the theory was not specifically designed and have implications for future research on identity theories of desistance as well as offender supervision practices. [ABSTRACT FROM AUTHOR]

Kimberlites are rare diamond-bearing volcanic rocks that originate as melts in the Earth's mantle. The original composition of kimberlitic melt is poorly constrained because of mantle and crustal contamination, exsolution of volatiles during ascent, and pervasive alteration during and after emplacement. One recent model (Russell et al. in Nature 481(7381):352-356, . doi:) proposes that kimberlite melts are initially carbonatitic and evolve to kimberlite during ascent through continuous assimilation of orthopyroxene and exsolution of CO. In high-temperature, high-pressure experiments designed to test this model, assimilation of orthopyroxene commences between 2.5 and 3.5 GPa by a reaction in which orthopyroxene reacts with the melt to form olivine, clinopyroxene, and CO. No assimilation occurs at 3.5 GPa and above. We propose that the clinopyroxene produced in this reaction can react with the melt at lower pressure in a second reaction that produces olivine, calcite, and CO, which would explain the absence of clinopyroxene phenocrysts in kimberlites. These experiments do not confirm that assimilation of orthopyroxene for the entirety of kimberlite ascent takes place, but rather two reactions at lower pressures (<3.5 GPa) cause assimilation of orthopyroxene and then clinopyroxene, evolving carbonatitic melts to kimberlite and causing CO exsolution that drives rapid ascent. [ABSTRACT FROM AUTHOR]

Core muscle injury/sports hernia/athletic pubalgia is an increasingly recognized source of pain, disability, and time lost from athletics. Groin pain among athletes, however, may be secondary to various etiologies. A thorough history and comprehensive physical examination, coupled with appropriate diagnostic imaging, may improve the diagnostic accuracy for patients who present with core muscular injuries. Outcomes of nonoperative management have not been well delineated, and multiple operative procedures have been discussed with varying return-to-athletic activity rates. In this review, we outline the clinical entity and treatment of core muscle injury and athletic pubalgia. In addition, we describe the relationship between athletic pubalgia and femoroacetabular impingement along with recent studies that have investigated the treatment of these related disorders. [ABSTRACT FROM AUTHOR]

Thrombocytosis and platelet hyperreactivity are known to be associated with malignancy; however, there have been no ultrastructure studies of platelets from patients with ovarian cancer. Here, we used electron cryotomography (cryo-ET) to examine frozen-hydrated platelets from patients with invasive ovarian cancer (n = 12) and control subjects either with benign adnexal mass (n = 5) or free from disease (n = 6). Qualitative inspections of the tomograms indicate significant morphological differences between the cancer and control platelets, including disruption of the microtubule marginal band. Quantitative analysis of subcellular features in 120 platelet electron tomograms from these two groups showed statistically significant differences in mitochondria, as well as microtubules. These structural variations in the platelets from the patients with cancer may be correlated with the altered platelet functions associated with malignancy. Cryo-ET of platelets shows potential as a noninvasive biomarker technology for ovarian cancer and other platelet-related diseases. [ABSTRACT FROM AUTHOR]

Breastfeeding tends to elicit strong feelings in mothers as well as impassioned rhetoric in our cultural discourse. Psychoanalytic thinkers have focused extensively on the infant's experience at the breast. Surprisingly, much less theoretical attention has been given to the mother's experience of breastfeeding. I begin with my own experience of struggling with this early stage of motherhood and with understanding why this act seemed to hold such emotional power. By tracing the theme of breastfeeding in Toni Morrison's Beloved, I attempt to draw out ideas about the breastfeeding mother as a subject rather than an object. I argue that the novel's depiction of breastfeeding supports understanding the maternal body as a source of ambivalence and creativity for the mother as well as for the infant. Drawing mainly on the work of Melanie Klein, Donald Winnicott and Julia Kristeva, I explore through literary readings how breastfeeding comes to stir up such passionate and often difficult feelings for mothers. [ABSTRACT FROM AUTHOR]

In this article, the author argues that there is something hypocritical with the U.S. government's refusal to enforce certain contracts on grounds of unconscionability under certain conditions. The author comments on the government's decision to enforce segregationist laws seems to deprive it of the moral standing to complain about the consequences of civil disobedience.

Objective: To assess the available literature evaluating the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with multiple daily insulin injections (MDII). Data Sources: A literature search of MEDLINE and Embase was performed (2004 to May 2020) using the following search terms: glucagon-like 1 receptor agonist, liraglutide, albiglutide, dulaglutide, exenatide, semaglutide, diabetes mellitus, and prandial insulin or bolus insulin. Additional references were obtained from cross-referencing the bibliographies of selected articles. Study Selection and Data Extraction: All information obtained from the searches were reviewed. All relevant trials are included in this review. Data Synthesis: Eight studies met criteria for inclusion. The addition of a GLP-1 RA to multiple daily insulin injections was associated with a reduction in A1c in 7 out of 8 studies, and weight loss in 5 studies. In studies that allowed insulin adjustment after the addition of GLP-1 RA, the average total daily insulin dose was reduced in 3 studies. When evaluated, hypoglycemia frequency or other adverse events were not increased when GLP-1 RAs were added to MDII. Relevance to Patient Care and Clinical Practice: Guidelines do not offer recommendations regarding the use of GLP-1 RAs in combination with MDII regimens. This review evaluates current studies demonstrating efficacy and safety considerations of this combination. Conclusions: While some studies did demonstrate an improvement in A1c and reduction in insulin doses without increased hypoglycemia, larger randomized controlled trials are needed to adequately assess the benefit and safety of GLP-1 RAs in combination with MDII. [ABSTRACT FROM AUTHOR]

Background:Osteochondritis dissecans (OCD) of the capitellum affects young athletes involved in elbow load-bearing activities. Unstable lesions are best managed surgically, although debate remains regarding the optimal method. Arthroscopic treatment allows rapid recovery, but the effect on the articular surface is undetermined.Hypothesis:The clinical outcome after arthroscopic microfracture of stage III/IV capitellum OCD would be successful in terms of return to sport and restoration of function, and there would be some evidence of articular restoration or repair.Study Design:Case series; Level of evidence, 4.Methods:We reviewed records of 10 consecutive adolescent patients (age ≤18 years) with stage III or IV OCD lesions of the capitellum managed with arthroscopic microfracture. The mean age at the time of surgery was 13.9 years (range, 10.8-18.5 years); 7 patients were skeletally immature and 3 were skeletally mature. Pre- and postoperative functional assessment included active range of motion, Mayo Elbow Performance Score (MEPS), and Timmerman/Andrews elbow score. All patients underwent plain radiographic and magnetic resonance imaging (MRI) evaluation at a minimum of 12 months (mean, 27 months; range, 12-49 months) and clinical evaluation at a minimum of 24 months (mean, 42 months; range, 27-54 months) after surgery.Results:The mean range of motion improved in both flexion (135.8°→140.7°, P = .112) and extension (20.4°→–2.2°, P = .005). The mean MEPS (70.5→97, P = .007) and Timmerman/Andrews elbow scores (116.4→193.0, P = .008) improved significantly. magnetic resonance imaging (MRI) evaluation demonstrated an improvement in overall joint congruence and the formation of a reparative articular surface in 8 of 10 (80%) patients. No reoperations or major complications were encountered. Six of 8 patients involved in competitive athletics returned to the same level of participation at an average of 5.1 months.Conclusion:Arthroscopic OCD fragment excision and capitellar microfracture demonstrates good to excellent functional results in short-term follow-up. Follow-up MRI suggests potential for a reparative fibrocartilaginous articular surface. Longer term follow-up is necessary to determine durability of the technique. [ABSTRACT FROM AUTHOR]

Delaying girls' early marriage is a critical public health and education goal in developing countries, in which their own or their mothers' education may play an important role. This paper reviews the existing evidence of any relationship between girls' schooling or women's literacy education and delayed marriage for themselves or their daughters. The majority of research reports focus on the correlation between girls' schooling and brides' age at first marriage. But it is conceivable that adult women's/mothers' literacy education also has considerable influence on the age at which their daughters are married. Since this aspect has hitherto not been explicitly investigated, the authors propose a model - based on relevant research about the outcomes of girls' schooling and women's literacy education - of the mechanisms that mediate between women's education and delayed marriage for their daughters. The authors argue for research that will inform policy makers interested in helping girls complete secondary schooling about the potential contributions of adult women's literacy education to this goal. [ABSTRACT FROM AUTHOR]

The synthesis, structural, and electronic properties of nine 1,3-diphenyl-6-alkyl/aryl substituted pentafulvenes were studied. Pyrene ring π-π interactions were revealed from analysis of the experimental crystal packing of 1,3-diphenyl-6-(1-pyrene)fulvene and supporting DFT calculations. Photophysical properties derived from UV-vis and fluorescence emission measurements demonstrated tunable and low HOMO-LUMO band gaps for the series. The presented results point to a model synthetic approach for incorporation of extended π systems and donor-π-acceptor groups for fulvene-based electronic materials. [ABSTRACT FROM AUTHOR]

Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear. Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained. Results: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumor-derived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis. Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. (Funded by the National Cancer Institute and others.) [ABSTRACT FROM PUBLISHER]

Background We investigated the clinical and biological significance of p130cas, an important cell signaling molecule, in ovarian carcinoma. Methods Expression of p130cas in ovarian tumors, as assessed by immunohistochemistry, was associated with tumor characteristics and patient survival. The effects of p130cas gene silencing with small interfering RNAs incorporated into neutral nanoliposomes (siRNA-DOPC), alone and in combination with docetaxel, on in vivo tumor growth and on tumor cell proliferation (proliferating cell nuclear antigen) and apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) were examined in mice bearing orthotopic taxane-sensitive (HeyA8 and SKOV3ip1) or taxane-resistant (HeyA8-MDR) ovarian tumors (n = 10 per group). To determine the specific mechanisms by which p130cas gene silencing abrogates tumor growth, we measured cell viability (MTT assay), apoptosis (fluorescence-activated cell sorting), autophagy (immunoblotting, fluorescence, and transmission electron microscopy), and cell signaling (immunoblotting) in vitro. All statistical tests were two-sided. Results Of 91 ovarian cancer specimens, 70 (76%) had high p130cas expression; and 21 (24%) had low p130cas expression. High p130cas expression was associated with advanced tumor stage (P < .001) and higher residual disease (>1 cm) following primary cytoreduction surgery (P = .007) and inversely associated with overall survival and progression-free survival (median overall survival: high p130cas expression vs low expression, 2.14 vs 9.1 years, difference = 6.96 years, 95% confidence interval = 1.69 to 9.48 years, P < .001; median progression-free survival: high p130cas expression vs low expression, 1.04 vs 2.13 years, difference = 1.09 years, 95% confidence interval = 0.47 to 2.60 years, P = .01). In mice bearing orthotopically implanted HeyA8 or SKOV3ip1 ovarian tumors, treatment with p130cas siRNA-DOPC in combination with docetaxel chemotherapy resulted in the greatest reduction in tumor growth compared with control siRNA therapy (92%–95% reduction in tumor growth; P < .001 for all). Compared with control siRNA therapy, p130cas siRNA-DOPC reduced SKOV3ip1 cell proliferation (31% reduction, P < .001) and increased apoptosis (143% increase, P < .001) in vivo. Increased tumor cell apoptosis may have persisted despite pan-caspase inhibition by the induction of autophagy and related signaling pathways. Conclusions Increased p130cas expression is associated with poor clinical outcome in human ovarian carcinoma, and p130cas gene silencing decreases tumor growth through stimulation of apoptotic and autophagic cell death. [ABSTRACT FROM PUBLISHER]

Abstract: We model the behavior of agents who care about receiving what they feel they deserve in a two-player rank-order tournament. Perceived entitlements are sensitive to how hard an agent has worked relative to her rival, and agents are loss averse around their meritocratically determined endogenous reference points. In a fair tournament sufficiently large desert concerns drive identical agents to push their effort levels apart in order to end up closer to their reference points on average. In an unfair tournament, where one agent is advantaged, the equilibrium is symmetric in the absence of desert, but asymmetric in the presence of desert. We find that desert concerns can undermine the standard conclusion that competition for a fixed supply of status is socially wasteful and explain why, when the distribution of output noise is fat-tailed, an employer might use a rank-order incentive scheme. [Copyright &y& Elsevier]

Summary: First-line chemotherapy fails in more than 20% of patients with epithelial ovarian cancer and about 40–50% of women who respond to initial treatment relapse within 2 years. In the recurrent setting, second-line chemotherapeutic agents have a 15–20% response rate with no cures. Fortunately, clinical investigations that have assessed the efficacy of new, biologically targeted therapies have reinvigorated therapeutic options for patients living with ovarian and other malignancies. In view of the fact that ovarian cancer is one of the most angiogenic neoplasms, there is great hope that implementing targeted agents with antiangiogenic properties will improve outcomes. However, as experience grows with the antitumour activity of these drugs, new toxic effects are emerging. The effects of antiangiogenic agents on molecules and processes that also have physiologically important roles in healthy tissues are at the crux of these toxic effects, or “collateral damage”. This review discusses the leading toxic effects encountered and anticipated in clinical investigation and practice with antiangiogenic agents in patients with ovarian cancer, with particular focus on potential management strategies. [Copyright &y& Elsevier]

Abstract: High content carbon nanotubes mats have been produced to a range of thicknesses and diameters by covalent bonded cross-linking of thiolated multi-walled carbon nanotubes. The Michael addition pathway was used to cross-link benzoquinone to thiol groups attached to the surface of the nanotubes. The mats were characterized by a variety of techniques including X-ray photoelectron spectroscopy, tensile strength as well as qualitative structural analysis by scanning electron microscopy. It was found that the optimum ratio by weight for cross-linking benzoquinone to thiolated carbon nanotubes was ca. 5:1. This work provided a simple route to the production of mats without high pressure processing or irradiation techniques generally used to produce Buckypaper which can require pressure control chambers, argon and hydrogen ion beams and high temperatures. The mat surface can be further functionalized with nanoparticles to form advanced carbon composite materials. [Copyright &y& Elsevier]