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Background: For many cancer survivors post-cure, chronic pain is a devastating complication of cancer treatment. The prevalence of chronic pain among cancer survivors is double that of the general population. However, little is known about the pain experience of cancer survivors who may have a different perspective than people with advanced cancer or people with noncancer pain. Objective: To understand the lived experience of chronic cancer-related pain in cancer survivors. Methods: We used a qualitative design with a descriptive phenomenological method to conduct in-depth interviews of 13 cancer survivors residing in the United States who completed curative cancer therapy, were at least three months from treatment, and experienced pain attributable to cancer. Data collection was focused on the lived experience and management of chronic cancer-related pain and a deep understanding of how the experience of chronic cancer-related pain shapes pain management choices. Results: The participants had a variety of primary cancer types and cancer pain syndromes. Three essential themes epitomized the experience of living with chronic cancer-related pain: invisible suffering at the cost of survival, an opioid paradox, and a lack of answers on what to expect and what might help. Conclusion and Implications: The results highlight an opportunity for pain self-management, education, and psychosocial interventions to optimize pain in cancer. Participants' experiences identify several opportunities to improve chronic cancer-related pain. Future efforts should prioritize access to multimodal pain treatments, high-quality communication, and expand clinicians' knowledge and skills to manage chronic pain. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and CD8+ T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment that disrupts the blood-tumor barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a "hot" tumor immune signature prior to losartan+anti-PDl therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients. [ABSTRACT FROM AUTHOR]

Objective Survivors of breast cancer with persistent cancer-related fatigue (CRF) report less exercise participation compared with survivors of breast cancer without CRF. Although CRF predicts other domains of self-efficacy among survivors, the effect of CRF on exercise self-efficacy (ESE)—an important predictor of exercise participation—has not been quantified. This study examined the relationship between CRF, ESE, and exercise participation and explored the lived experience of engaging in exercise among survivors of breast cancer with persistent CRF. Methods Fifty-eight survivors of breast cancer (3.7 [SD = 2.4] years after primary treatment) self-reported CRF, ESE, and exercise participation (hours of moderate-intensity exercise per week). Regression and mediation analyses were conducted. Survivors who reported clinically significant CRF and weekly exercise were purposively sampled for 1-on-1 interviews (N = 11). Thematic analysis was performed across participants and within higher versus lower ESE subsets. Results Greater CRF predicted lower ESE (β  = −0.32) and less exercise participation (β  = −0.08). ESE mediated the relationship between CRF and exercise participation (β  = −0.05, 95% CI = −0.09 to −0.02). Qualitative data showed that survivors of breast cancer with higher ESE perceived exercise as a strategy to manage fatigue, described self-motivation and commitment to exercise, and had multiple sources of support. In contrast, survivors with lower ESE described less initiative to manage fatigue through exercise, greater difficulty staying committed to exercise, and less support. Conclusions Survivors of breast cancer with persistent CRF may experience decreased ESE, which negatively influences exercise participation. Clinicians should screen for or discuss confidence as it relates to exercise and consider tailoring standardized exercise recommendations for this population to optimize ESE. This may facilitate more sustainable exercise participation and improve outcomes. Impact This study highlights the behavioral underpinnings of CRF as a barrier to exercise. Individualized exercise tailored to optimize ESE may facilitate sustainable exercise participation among survivors of breast cancer with CRF. Strategies for clinicians to address ESE are described and future research is suggested. Lay Summary Women with fatigue after breast cancer treatment may have lower confidence about their ability to engage in exercise. Individually tailoring exercise to build confidence as it relates to exercise may result in more consistent exercise and better health-related outcomes. [ABSTRACT FROM AUTHOR]

While agricultural services are shrinking, the number of nontraditional farms run by immigrant farmers is rising in U.S. suburban regions. This study attempts to understand Chinese immigrant farmers' experience accessing agricultural services and resources in the New York metropolitan area and explores the need for changes in agricultural services to meet changing demand. Thirteen Chinese immigrant farmers in the region were recruited to participate in a semi-structured interview to understand their shared experiences of accessing agricultural services and resources. The study identified diverse ways of accessing agricultural services and resources in four critical areas of farming operations: agricultural technology, financial services, farm labor, and farming machinery; and also revealed the existence of "liability of newness" among those new immigrant farmers in operating farms. Most participants felt that they were isolated, with limited access to available services as new immigrant farmers, which constitutes the liabilities to their success in farming. Language barriers, cultural differences, distrust, and isolation were the main obstacles to access adequate services and resources. As farms and farmers are becoming more diverse in U.S. suburban regions, the provision of agricultural services needs to adapt accordingly to meet the growing needs of groups of farmers with varying farming experiences and demographic backgrounds and help them to overcome the liabilities as new immigrant farmers. This study contributes to understanding the farming experiences of minority farm groups, which help develop more inclusive agricultural services. [ABSTRACT FROM AUTHOR]

This study aims to synthesize bismuth oxide/activated carbon composites composed of rice husks for battery anodes and to determine the effect of bismuth nitrate pentahydrate mole variations on the characteristics of the resulting composites. The bismuth oxide/activated carbon composite synthesis was carried out using bismuth nitrate pentahydrate, sodium sulfate, and sodium hydroxide precursors, which were mixed with rice husk-based activated carbon. A variation was made for the mole of bismuth nitrate pentahydrate used, while the compositions of activated carbon and other precursors were made fixed. The composites were synthesized via the hydrothermal method at a temperature of 110°C for 5 hours. The results illustrate that bismuth oxide is successfully formed as a composite in the 8 mmol variation with a composite electrical conductivity value of 2:40 × 10-3 S.m-1. [ABSTRACT FROM AUTHOR]

Introduction: Sex education is important to support healthy sexual development/behaviors among heterosexual and sexual minority youth. Efforts to assess the efficacy of different sex education programs have been complicated by the lack of an established and detailed way to characterize overall sex education content. Methods: This study delineates seven different types of sex education and compares the impact of education types on the probability of sexual intercourse and contraceptive method use among a nationally representative sample of females aged 15–19 years. Data were obtained from four National Survey of Family Growth surveys (2011–2019). Multinomial logistic regression was used to examine associations and calculate predicted probability values. Results: Among youth in this analysis (N = 3952), 14.9% identified as a sexual minority and 72% reported sex education including refraining from sex, contraception, and STIs/HIV. Compared to their heterosexual peers, sexual minorities were more likely to report no sex education and less likely to report receipt of abstinence-only education. All types of education, except education solely focused on refraining from sex and contraception methods, had a statistically significant effect on sexual behavioral outcomes (intercourse in the past 12 months and type of contraceptive use) as compared to no sex education. Conclusions: Findings highlight the need for consideration of the specific/total content of sex education, benefits/drawbacks of sex education types, and the needs of sexual minority youth. Policy Implications: Research is needed to further explore outcomes associated with specific curricular content. Specific content of sex education should be considered prior to making curricular policies decisions. [ABSTRACT FROM AUTHOR]

Background: Sagittal fractures of equine cheek teeth are commonly observed during oral examination. There are few reports on the apical and endodontic pathology associated with such fractures seen during computed tomographic (CT) examination. Objectives: This study aimed to document the prevalence of CT changes indicative of apical disease in equine cheek teeth, which have suffered a sagittal fracture involving the clinical ± reserve crown. Study design: This study is a retrospective case series. Methods: CT examinations of equine heads with sagittal fractures of cheek teeth present were reviewed: 81 teeth from 49 horses were identified to have a sagittal cheek tooth fracture. The images were evaluated for apical pathology including gas (in the endodontic system and periapically), widened periodontal space, periapical sclerosis, apical clubbing, cementoma/hypercementosis, lamina dura loss, associated sinusitis and sinus mucosal swelling. An apical infection grading system was created to give each tooth a score. Hounsfield units were used to measure the density of the endodontic, apical and periapical regions. The fracture length ratio was recorded. Statistical analysis was performed using a generalised estimating equation to evaluate predictors of apical infection and associations between clinical signs and CT abnormalities. Results: Eighty‐seven sagittal fractures (56 buccal, 17 palatal/lingual and 14 midline) from 81 teeth were recorded (74 maxillary and 7 mandibular). Apical infection was diagnosed in 73% (37/51, P =.05) of buccal, 55% (6/11, P =.07) of palatal/lingual, 100% (13/13) of midline, 100% (6/6) of multiple fractures and 96% (23/24, P =.008) of fractures involving infundibula. There was no significant relationship between apical infection and the presence of clinical signs associated with dental pathology (P =.4). There was no significant association between fracture length ratio and apical infection (P = 1.0). Midline sagittal fractures were significantly associated with sinusitis when compared with all other maxillary fractures (odds ratio [OR] 5.92, 95% confidence interval [CI] 1.67‐20.83, P =.006). Loss of the lamina dura was not significantly associated with apical infection (P =.5). Main limitations: There is a maxillary cheek tooth bias in the data set and the subjective grading system. Conclusions: A large proportion of fractured cheek teeth have evidence of apical infection on CT examination and therefore warrant treatment. [ABSTRACT FROM AUTHOR]

Progress in medical and surgical care has tremendously improved the survival rates of children with congenital heart disease (CHD). However, reduced aerobic capacity and health-related issues remain a threaten to quality survival and prevention of related complications among children and adolescents with CHD. This research program aims to develop and evaluate a WeChat-based health platform (HeartFIT) to facilitate cardiac rehabilitation and promote physical fitness for this rapidly expanding young population. The study protocol describes the use of an iterative process of using a mixed-methods strategy to develop, refine, and pilot test the proposed HeartFIT platform. A sequential problem-solving process comprising four iterative phases with ongoing end-user input will be implemented. In phase 1, relevant literature was systematically reviewed (completed) and then child-parent dyads will be interviewed to understand the broad context and the requirements and considerations of the target population toward the WeChat-based rehabilitation platform. In phase 2, key features and priority functionalities for the platform will be ideated and refined, and a digital interactive prototype will be created. In phase 3, heuristic evaluation and three rounds of end-user testing will be conducted to ensure further refinement and usability of the prototype. In phase 4, a prospective pilot study will be performed to investigate the feasibility, acceptability, and preliminary efficacy of the developed platform over a 12-week intervention period. If HeartFIT intervention is feasible, acceptable, and demonstrates promising efficacy, an adequately powered randomized controlled trial (future work) will be deployed to test the real-world effectiveness of the intervention. [ABSTRACT FROM AUTHOR]

In acute stroke care two proven reperfusion treatments exist: (1) a blood thinner and (2) an interventional procedure. The interventional procedure can only be given in a stroke centre with specialized facilities. Rapid initiation of either is key to improving the functional outcome (often emphasized by the common phrase in acute stroke care "time=brain"). Delays between the moment the ambulance is called and the initiation of one or both reperfusion treatment(s) should therefore be as short as possible. The speed of the process strongly depends on five factors: patient location, regional patient allocation by emergency medical services (EMS), travel times of EMS, treatment locations, and in-hospital delays. Regional patient allocation by EMS and treatment locations are sub-optimally configured in daily practice. Our aim is to construct a mathematical model for the joint decision of treatment locations and allocation of acute stroke patients in a region, such that the time until treatment is minimized. We describe acute stroke care as a multi-flow two-level hierarchical facility location problem and the model is formulated as a mixed integer linear program. The objective of the model is the minimization of the total time until treatment in a region and it incorporates volume-dependent in-hospital delays. The resulting model is used to gain insight in the performance of practically oriented patient allocation protocols, used by EMS. We observe that the protocol of directly driving to the nearest stroke centre with special facilities (i.e., the mothership protocol) performs closest to optimal, with an average total time delay that is 3.9% above optimal. Driving to the nearest regional stroke centre (i.e., the drip-and-ship protocol) is on average 8.6% worse than optimal. However, drip-and-ship performs better than the mothership protocol in rural areas and when a small fraction of the population (at most 30%) requires the second procedure, assuming sufficient patient volumes per stroke centre. In the experiments, the time until treatment using the optimal model is reduced by at most 18.9 minutes per treated patient. In economical terms, assuming 150 interventional procedures per year, the value of medical intervention in acute stroke can be improved upon up to € 1,800,000 per year. [ABSTRACT FROM AUTHOR]

Background: Chronic low back pain (CLBP) prevalence has steadily increased over the last two decades. Manual therapy (MT) is recommended within a multimodal management approach to improve pain and disability although evidence investigating the patients' experience of MT is scarce.Objective: To explore expectations and perceptions of MT techniques in people with CLBP.Methods: A qualitative study embedded sequential to an experimental trial using semi-structured interviews (SSI) explored participants' experiences of thrust, non-thrust and sham technique. Purposive sampling enabled variance in age and CLBP duration. An evidence informed topic guide was used. Data were analysed using thematic analysis (TA). Respondent validation and peer debriefing enhanced trustworthiness. The Consolidating Criteria for Reporting Qualitative Studies (COREQ) reported methodological rigour.Findings: Ten participants (50% male) with a mean age of 29.1 years (Standard Deviation (SD): 7.9, range: 19-43), a mean pain intensity of 4.5 on a Numeric Rating Scale (NRS) 0-10 (SD: 1.5, range: 2-7), a mean Oswestry Disability Score (ODI) of 9 (SD: 4.6, range: 2-17) and a mean Tampa Scale of Kinesiophobia (TSK) score of 38.6 (SD: 4.8, range: 30-45) participated. Four themes were identified: understanding of pain; forming expectations; perception of care; re-evaluation of body awareness and management. Understanding of CLBP is formed by an individuals' pain perception and exchange with social environment. This, combined with communication with physiotherapist influenced expectations regarding the MT technique.Conclusion: Expectations for MT were formed by an individual's social environment and previous experience. A treatment technique is perceived as positive if its characteristics are aligned with the individual's understanding of pain and if care is delivered in an informative and reassuring manner. [ABSTRACT FROM AUTHOR]

Purpose of the Study: More than 50% of breast cancer survivors without a diagnosis of lymphedema suffer daily from numerous and co-occurring lymphedema symptoms. This study aimed to identify lymphedema symptom patterns and the association of such patterns with phenotypic characteristics and biomarkers using latent class analysis (LCA). A prospective, descriptive, and repeated-measure design was used to enroll 140 women and collect data. Recent Findings: LCA identified three distinct lymphedema symptom classes at 8 weeks and 12 months post-surgery: low, moderate, and severe symptom classes and associated phenotypic characteristics. Participants were more likely to be in the severe symptom classes at 12 months post-surgery if they had lower education level, cording, an axillary syndrome at 8 weeks post-surgery, neoadjuvant chemotherapy, and radiation. Summary: Pre-surgery level of IL1-a, IL-6, IL-8, and VEGF was associated with the severe symptom class at 8 weeks post-surgery, suggesting that such biomarkers may be used to predict risk for lymphedema symptoms. [ABSTRACT FROM AUTHOR]

Background: The-Optimal-Lymph-Flow (TOLF) intervention aims to promote lymph flow through therapeutic lymphatic exercises to relieve lymphatic pain, swelling, lymphedema symptoms, and to decrease lymph fluid levels among breast cancer survivors. To enhance the efficacy of the TOLF intervention, an innovative, intelligent, Kinect-enhanced lymphatic exercise intervention (Kinect-TOLF) was developed to teach patients to perform the lymphatic exercises correctly. Objectives: This feasibility trial aimed to determine the feasibility, usability, and effects of the Kinect-TOLF on lymphatic pain, swelling, lymphedema symptoms, and lymph fluid levels. Methods: A single-arm feasibility trial with a pre- and post-test design was employed to recruit 30 breast cancer survivors with persistent lymphatic pain or swelling. Patients received a single training session to learn how to perform the lymphatic exercises using the Kinect-TOLF program. Descriptive statistics, Wilcoxon signed-rank tests, t -test, Spearman's rank correlation coefficients, linear regressions, and Cohen's d were performed for data analysis. Qualitative data were assessed for common themes. Results: The Kinect-TOLF was effective in training patients to perform the lymphatic exercises correctly with high user satisfaction. Significant reductions were found in scores of lymphatic pain (Med Δ = −1.00, CI = [−1.5, −0.1], P =.004), arm/hand swelling (Med Δ = −1.00, CI = [−1.5, −0.5], P =.004), total swelling (Med Δ = −1.5, CI = [−2.0, −1.0], P =.003), number of lymphedema symptoms (M Δ = −3.8, CI = [−5.5, −2.1], P <.001), and lymphedema symptom severity (M Δ = −5.3, CI = [−9.5, −1.1], P =.016). A significant reduction in lymph fluid levels was found in mean L-Dex scores (M Δ = −2.68, CI = [−4.67, −0.69], P =.010). Greater decrease in mean L-Dex scores were found in patients with abnormal lymph fluid levels (L-Dex ≥ 7.1) (M Δ = −5.19, CI = [−1.75, −8.63], P =.008). Patients' qualitative feedback supported the results of the study. Conclusions: The Kinect-TOLF is safe, feasible, and effective in reducing lymphatic pain, swelling, lymphedema symptoms, and in decreasing lymph fluid levels. Future research should focus on a randomized clinical trial to confirm the unique or synergistic efficacy of the Kinect-TOLF in comparison with current lymphedema treatment and other forms of exercises or movement therapy. This study was registered in ClinicalTrials.gov with US ClinicalTrials.gov Identifier: NCT03999177. [ABSTRACT FROM AUTHOR]

This study explored the association between oral microbes and head and neck cancer (HNC) as well as symptoms related to patients with HNC before surgical treatment. Fifty-six patients with HNC and 64 matched healthy controls were recruited from West China hospital in Southwest China. The demographic, clinical, and symptom data were collected. Salivary samples were collected to determine the microbial characteristics using 16S rRNA gene sequencing. Patients with HNC presented increased Capnocytophaga abundances. The oral microbial markers as Capnocytophaga (area under the curve=0.81) achieved a high classification power between the HNC patients and healthy controls. Moreover, using Capnocytophaga in conjunction with symptom of voice/speech difficulty achieved an overall predicting accuracy of 92.5% comparing with using Capnocytophaga alone (79.2% accuracy) in distinguishing the HNC patients from healthy controls. Salivary microbial profiles and HNC symptoms may be potential biomarkers for HNC screening. [ABSTRACT FROM AUTHOR]

Introduction: Malignant fungating wounds (MFWs), non-healing wounds caused by aggressive proliferation of malignant tumors, afflict 5%–14.5% of patients with advanced cancer. We conducted an integrative review to evaluate the level of evidence of peer-reviewed literature published from 2000 to 2019 on symptoms of MFWs, and the impact of the symptoms on functional performance among patients with advanced cancer. Methods: Four electronic databases were searched and 1506 articles were retrieved. A total of 1056 abstracts were screened for relevance and a full review of the 26 articles was performed. A total of 12 articles met inclusion criteria. An established quality assessment tool was used to rate the quality of the included studies. Results: The overall quality of the included 12 studies was adequate. This integrative review of the literature provided strong evidence that patients with MFWs suffered multiple symptoms, including pain, odor, exudate, bleeding, pruritus, perceived wound status, perceived bulk effect and lymphedema. Quantitative research was not able to capture the occurrence and characteristics of all the identified symptoms. There was a lack of quantitative research on the impact of MFWs and symptoms on patients' functional performance. Yet, qualitative studies provided vivid description of how the symptoms negatively affected patients' functional performance. Future research should develop a clinical tool that enables the comprehensive assessment of symptoms of MFWs. Well-designed quantitative research is needed to delineate the impact of symptoms of MFWs on patients' functional performance to ensure quality palliative care. [ABSTRACT FROM AUTHOR]

This pilot, double-blind, randomized, placebo-controlled study is aimed at evaluating the effectiveness of low-level laser therapy (LLLT) as a complementary treatment to complete decongestive therapy (CDT) treating lymphedema among breast cancer patients for 12 months post-intervention. Study population was breast cancer patients who were diagnosed and referred to lymphedema clinic for CDT. Participants (n = 22) were randomized and assigned into either an active laser intervention group or an inactive laser placebo-control group. Active LLLT was administered to participants twice a week at the beginning of each CDT session. Outcome measures included lymphedema symptoms, symptom distress, and limb volume by an infrared perometer. Participants in the active and placebo laser groups were comparable in demographic and clinical predictors of lymphedema. In comparison with the placebo group (83.3%), significantly fewer participants in the active laser group (55.6%) reported more than one lymphedema symptom (p = 0.012) at 12 months post-intervention. Significantly, more patients in the active laser group (44.4%) reported less than two impaired limb mobility symptoms in comparison with the placebo group (33.3%) at 12 months post-intervention (p = 0.017). The active laser group had statistically significant improvements in symptom distress of sadness (p = 0.005) from 73 to 11% and self-perception (p = 0.030) from 36 to 0% over time from baseline to 12-months post-intervention. There was no significant reduction in limb volume. Findings of the trial demonstrated significant benefits of complementary LLLT for relieving symptoms and improvement of emotional distress in breast cancer patients with lymphedema. [ABSTRACT FROM AUTHOR]

We address the problem of ambulance dispatching, in which we must decide which ambulance to send to an incident in real time. In practice, it is commonly believed that the 'closest idle ambulance' rule is near-optimal and it is used throughout most literature. In this paper, we present alternatives to the classical closest idle ambulance rule. Most ambulance providers as well as researchers focus on minimizing the fraction of arrivals later than a certain threshold time, and we show that significant improvements can be obtained by our alternative policies. The first alternative is based on a Markov decision problem (MDP), that models more than just the number of idle vehicles, while remaining computationally tractable for reasonably-sized ambulance fleets. Second, we propose a heuristic for ambulance dispatching that can handle regions with large numbers of ambulances. Our main focus is on minimizing the fraction of arrivals later than a certain threshold time, but we show that with a small adaptation our MDP can also be used to minimize the average response time. We evaluate our policies by simulating a large emergency medical services region in the Netherlands. For this region, we show that our heuristic reduces the fraction of late arrivals by 18 % compared to the 'closest idle' benchmark policy. A drawback is that this heuristic increases the average response time (for this problem instance with 37 %). Therefore, we do not claim that our heuristic is practically preferable over the closest-idle method. However, our result sheds new light on the popular belief that the closest idle dispatch policy is near-optimal when minimizing the fraction of late arrivals. [ABSTRACT FROM AUTHOR]

We study the Dynamic Ambulance Management (DAM) problem in which one tries to retain the ability to respond to possible future requests quickly when ambulances become busy. To this end, we need models for relocation actions for idle ambulances that incorporate different performance measures related to response times. We focus on rural regions with a limited number of ambulances. We model the region of interest as an equidistant graph and we take into account the current status of both the system and the ambulances in a state. We do not require ambulances to return to a base station: they are allowed to idle at any node. This brings forth a high degree of complexity of the state space. Therefore, we present a heuristic approach to compute redeployment actions. We construct several scenarios that may occur one time-step later and combine these scenarios with each feasible action to obtain a classification of actions. We show that on most performance indicators, the heuristic policy significantly outperforms the classical compliance table policy often used in practice. [ABSTRACT FROM AUTHOR]

Malignant fungating wounds present in 5–14% of advanced cancer patients in the United States and are a result of cancerous cells infiltrating and proliferating in the skin. Presentation of malignant fungating wounds often occurs in the last 6 months of life and therefore become symbols of impending death for patients and their families. Due to the incurable and severe nature of these wounds, patients require palliative care until death to minimize pain and suffering. Symptoms associated with these chronic wounds include malodor, pain, bleeding, necrosis, large amounts of exudate, increased microbial growth, and more. Limited research using culture-based techniques has been conducted on malignant fungating wounds and therefore no optimal approach to treating these wounds has been established. Despite limited data, associations between the cutaneous microbiome of these wounds and severity of symptoms have been made. The presence of at least one strain of obligate anaerobic bacteria is linked with severe odor and exudate. A concentration of over 105/g bacteria is linked with increased pain and exudate. Bacterial metabolites such as DMTS and putrescine are linked with components of malignant fungating wound odor and degradation of periwound skin. The few but significant associations made between the malignant fungating wound microbiome and severity of symptoms indicate that further study on this topic using 16S rRNA gene sequencing may reveal potential therapeutic targets within the microbiome to significantly improve current methods of treatment used in the palliative care approach. [ABSTRACT FROM AUTHOR]

Background: Awareness of disease status has been identified as a factor in the treatment decision-making process. Women with recurrent ovarian cancer are facing the challenge of making treatment decisions throughout the disease trajectory. It is not understood how women with ovarian cancer perceive their disease and subsequently make treatment decisions. Purpose: The purpose of this phenomenological study was to understand the lived experience of women with recurrent ovarian cancer, how they understood their disease and made their treatment decisions. Methods: A qualitative design with a descriptive phenomenological method was used to conduct 2 in-depth interviews with 12 women (n = 24 interviews). Each interview was ∼60 minutes and was digitally recorded and professionally transcribed. Data collection focused on patients' understanding of their disease and how patients participated in treatment decisions. A modified version of Colaizzi's method of phenomenological reduction guided data analysis. Results: Three themes emerged to describe the phenomenon of being aware of disease status: (1) perceiving recurrent ovarian cancer as a chronic illness, (2) perceived inability to make treatment decisions, and (3) enduring emotional distress. Conclusions and Implications: This study revealed how 12 women conceptualized recurrent ovarian cancer as a chronic disease and their perceived inability to make treatment decisions because of lack of information and professional qualifications, resulting in enduring emotional distress. Future research should replicate the study to confirm the persistence of the themes for racially, ethnically, and religiously diverse patient samples and to improve understanding of awareness of disease status and decision-making processes of patients. [ABSTRACT FROM AUTHOR]

Metastatic breast cancers (mBCs) are largely resistant to immune checkpoint blockade, but the mechanisms remain unclear. Primary breast cancers are characterized by a dense fibrotic stroma, which is considered immunosuppressive in multiple malignancies, but the stromal composition of breast cancer metastases and its role in immunosuppression are largely unknown. Here we show that liver and lung metastases of human breast cancers tend to be highly fibrotic, and unlike primary breast tumors, they exclude cytotoxic T lymphocytes (CTLs). Unbiased analysis of the The Cancer Genome Atlas database of human breast tumors revealed a set of genes that are associated with stromal T-lymphocyte exclusion. Among these, we focused on CXCL12 as a relevant target based on its known roles in immunosuppression in other cancer types. We found that the CXCL12 receptor CXCR4 is highly expressed in both human primary tumors and metastases. To gain insight into the role of the CXCL12/CXCR4 axis, we inhibited CXCR4 signaling pharmacologically and found that plerixafor decreases fibrosis, alleviates solid stress, decompresses blood vessels, increases CTL infiltration, and decreases immunosuppression in murine mBC models. By deleting CXCR4 in αSMA+ cells, we confirmed that these immunosuppressive effects are dependent on CXCR4 signaling in αSMA+ cells, which include cancer-associated fibroblasts as well as other cells such as pericytes. Accordingly, CXCR4 inhibition more than doubles the response to immune checkpoint blockers in mice bearing mBCs. These findings demonstrate that CXCL12/CXCR4-mediated desmoplasia in mBC promotes immunosuppression and is a potential target for overcoming therapeutic resistance to immune checkpoint blockade in mBC patients. [ABSTRACT FROM AUTHOR]

Purpose: Pap smear screening programs have been ineffective in reducing cervical cancer mortality in most Latin American and Caribbean countries, in part due to low screening rates. The purpose of this review was to analyze recent studies to identify demographic, social, and cultural factors influencing women’s participation in Pap screening programs in Latin America and the Caribbean. Design/Method: For this integrative review, cervical cancer screening in Latin America and the Caribbean was searched using PubMed, CINAHL, EMBASE, and PsycINFO databases. Findings/Results: Demographic barriers to screening were socioeconomic status, education, race/ethnicity, and geography. Social barriers included lack of uniformity in screening guidelines, lack of knowledge regarding cervical cancer, and lack of preventive culture. Cultural barriers were fear/embarrassment and gender roles. Conclusions: There are multilevel barriers to Pap smear utilization among women in Latin America and the Caribbean. Implications for Practice: Findings highlight a need for health system engagement, promotion of preventive care, and community-generated educational programs and solutions. [ABSTRACT FROM AUTHOR]

Anaerobic digestion (AD) uses a range of substrates to generate biogas, including energy crops such as globally abundant rice straw (RS). Unfortunately, RS is high in lignocellulosic material and has high to C:N ratios (~80:1), which makes it (alone) a comparatively poor substrate for AD. Co-digestion with dairy manure (DM) has been promoted as a method for balancing C:N ratios to improve RS AD whilst also treating another farm waste and co-producing a potentially useful fertiliser. However, past co-digestion studies have not directly compared RS AD microbial communities with and without DM additions, which has made it hard to assess all impacts of DM addition to RS AD processes. Here, four RS:DM ratios were contrasted in identical semi-continuous-fed AD bioreactors, and 100% RS was found to produce the highest specific methane yields (112 mL CH4/g VS/day; VS, volatile solids), which is over double yields achieved in the reactor with the highest DM content (30:70 RS:DM by mass; 48 mL CH4/g VS/day). To underpin these data, microbial communities were sequenced and characterised across the four reactors. Dominant operational taxonomic units (OTUs) in the 100% RS unit were Bacteroidetes/Firmicutes, whereas the 30:70 RS:DM unit was dominated by Proteobacteria/Spirochaetes, suggesting major microbial community shifts occur with DM additions. However, community richness was lowest with 100% RS (despite higher specific yields), suggesting particular OTUs may be more important to yields than microbial diversity. Further, ambient VFA and VS levels were significantly higher when no DM was added, suggesting DM-amended reactors may cope better with higher organic loading rates (OLR). Results show that RS AD without DM addition is feasible, although co-digestion with DM will probably allow higher OLRs, resulting in great RS throughput in farm AD units. [ABSTRACT FROM AUTHOR]

Various systems across a broad range of applications contain tandem queues. Strong dependence between the servers has proven to make such networks complicated and difficult to study. Exact analysis is rarely computationally tractable and sometimes not even possible. Nevertheless, as it is most often the case in reality, there are costs associated with running such systems, and therefore, optimizing the control of tandem queues is of main interest from both a theoretical and a practical point of view. Motivated by this, the present paper considers a tandem queueing network with linear holding costs and a startup cost for the second server. In our work, we present a rather intuitive, easy to understand, and at the same time very accurate technique to approximate the optimal decision policy. Extensive numerical experimentation shows that the approximation works extremely well for a wide range of parameter combinations. [ABSTRACT FROM AUTHOR]

There are risks from disease in undertaking wild animal reintroduction programmes. Methods of disease risk analysis have been advocated to assess and mitigate these risks, and post-release health and disease surveillance can be used to assess the effectiveness of the disease risk analysis, but results for a reintroduction programme have not to date been recorded. We carried out a disease risk analysis for the reintroduction of pool frogs ( Pelophylax lessonae) to England, using information gained from the literature and from diagnostic testing of Swedish pool frogs and native amphibians. Ranavirus and Batrachochytrium dendrobatidis were considered high-risk disease threats for pool frogs at the destination site. Quarantine was used to manage risks from disease due to these two agents at the reintroduction site: the quarantine barrier surrounded the reintroduced pool frogs. Post-release health surveillance was carried out through regular health examinations of amphibians in the field at the reintroduction site and collection and examination of dead amphibians. No significant health or disease problems were detected, but the detection rate of dead amphibians was very low. Methods to detect a higher proportion of dead reintroduced animals and closely related species are required to better assess the effects of reintroduction on health and disease. [ABSTRACT FROM AUTHOR]

Piezoelectricity takes part in multiple important functions and processes in biomaterials often vital to the survival of organisms. Here, we investigate the piezoelectric properties of fish scales of green carp by directly examining their morphology at nanometer levels. Two types of regions are found to comprise the scales, a smooth one and a rough one. The smooth region is comprised of a ridge and trough pattern and the rough region characterized by a flat base with an elevated mosaic of crescents. Piezoelectricity is found on the ridges and base regions of the scales. From clear distinctions between the composition of the inner and outer surfaces of the scales, we identify the piezoelectricity to originate from the presence of hydroxyapatite which only exists on the surface of the fish scales. Our findings reveal a different mechanism of how green carp are sensitive to their surroundings and should be helpful to studies related to the electromechanical properties of marine life and the development of bio-inspired materials. [ABSTRACT FROM AUTHOR]

This article studies the heavy-traffic (HT) behavior of queueing networks with a single roving server. External customers arrive at the queues according to independent renewal processes and after completing service, a customer either leaves the system or is routed to another queue. This type of customer routing in queueing networks arises very naturally in many application areas (in production systems, computer- and communication networks, maintenance, etc.). In these networks, the single most important characteristic of the system performance is oftentimes the path time, i.e., the total time spent in the system by an arbitrary customer traversing a specific path. The current article presents the first HT asymptotic for the path-time distribution in queueing networks with a roving server under general renewal arrivals. In particular, we provide a strong conjecture for the system’s behavior under HT extending the conjecture of Coffman et al.[8,9]to the roving server setting of the current article. By combining this result with novel light-traffic asymptotics, we derive an approximation of the mean path time for arbitrary values of the load and renewal arrivals. This approximation is not only highly accurate for a wide range of parameter settings, but is also exact in various limiting cases. [ABSTRACT FROM PUBLISHER]

Currently, no targeted therapies are available for metastatic triplenegative breast cancer (mTNBC). We evaluated the safety, efficacy, and biomarkers of response to cabozantinib, a multikinase inhibitor, in patients with mTNBC. We conducted a single arm phase II and biomarker study that enrolled patients with measurable mTNBC. Patients received cabozantinib (60 mg daily) on a 3-week cycle and were restaged after 6 weeks and then every 9 weeks. The primary endpoint was objective response rate. Predefined secondary endpoints included progression-free survival (PFS), toxicity, and tissue and blood circulating cell and protein biomarkers. Of 35 patients who initiated protocol therapy, 3 (9% [95% confidence interval (CI): 2, 26]) achieved a partial response (PR). Nine patients achieved stable disease (SD) for at least 15 weeks, and thus the clinical benefit rate (PR+SD) was 34% [95% CI: 19, 52]. Median PFS was 2.0 months [95% CI: 1.3, 3.3]. The most common toxicities were fatigue, diarrhea, mucositis, and palmar-plantar erythrodysesthesia. There were no grade 4 toxicities, but 12 patients (34%) required dose reduction. Two patients had TNBCs with MET amplification. During cabozantinib therapy, there were significant and durable increases in plasma placental growth factor, vascular endothelial growth factor (VEGF), VEGF-D, stromal cell-derived factor 1a, and carbonic anhydrase IX, and circulating CD3 + cells and CD8 + T lymphocytes, and decreases in plasma soluble VEGF receptor 2 and CD14+ monocytes (all p < .05). Higher baseline concentrations of soluble MET (sMET) associated with longer PFS ( p = .03). In conclusion, cabozantinib showed encouraging safety and efficacy signals but did not meet the primary endpoint in pretreated mTNBC. Exploratory analyses of circulating biomarkers showed that cabozantinib induces systemic changes consistent with activation of the immune system and antiangiogenic activity, and that sMET should be further evaluated a potential biomarker of response. The Oncologist 2017;22:25-32 Implications for Practice: Triple-negative breast cancer (TNBC)-a disease with a dearth of effective therapies-often overexpress MET, which is associated with poor clinical outcomes. However, clinical studies of agents targeting MET and VEGF pathways-alone or in combination-have shown disappointing results. This study of cabozantinib (a dual VEGFR2/MET) in metastatic TNBC, while not meeting its prespecified endpoint, showed that treatment is associated with circulating biomarker changes, and is active in a subset of patients. Furthermore, this study demonstrates that cabozantinib therapy induces a systemic increase in cytotoxic lymphocyte populations and a decrease in immunosuppressive myeloid populations. This supports the testing of combinations of cabozantinib with immunotherapy in future studies in breast cancer patients. [ABSTRACT FROM AUTHOR]

In anaerobic digesters, temperature fluctuation could lead to process instability and failure. It is still not well understood how digester microbiota as a whole respond to heat shock, and what specific organisms are vulnerable to perturbation or responsible for process recovery after perturbation. To address these questions, a mesophilic benzoate-degrading methanogenic culture enriched from digester was subjected to different levels of heat shock. Three types of methane production profiles after perturbation were observed in comparison to the control: uninhibited, inhibited with later recovery, and inhibited without recovery. These responses were correlated with the microbial community compositions based on the analyses of 16S rRNA and 16S rRNA gene. Specifically, the primary benzoate-degrading syntroph was highly affected by heat shock, and its abundance and activity were both crucial to the restoration of benzoate degradation after heat shock. In contrast, methanogens were stable regardless whether methane production was inhibited. Populations related to ' Candidatus Cloacimonetes' and Firmicutes showed stimulated growth. These observations indicated distinct physiological traits and ecological niches associated with individual microbial groups. The results obtained after exposure to heat shock can be critical to more comprehensive characterization of digester ecology under perturbations. Significance and Impact of the Study Anaerobic digestion is an essential step in municipal wastewater treatment owing to its striking capacity of reducing wasted sludge and recovering energy. However, as an elaborate microbial process, it requires constant temperature control and is sensitive to heat shock. In this study, we explored the microbial response to heat shock of a methanogenic culture enriched from anaerobic digester sludge. Microorganisms that were vulnerable to perturbation or responsible for process recovery after perturbation were identified. [ABSTRACT FROM AUTHOR]

We study cyclic polling models with exhaustive service at each queue under a variety of non-FCFS (first-come-first-served) local service orders, namely last-come-first-served with and without preemption, random-order-of-service, processor sharing, the multi- class priority scheduling with and without preemption, shortest-job-first, and the shortest remaining processing time policy. For each of these policies, we first express the waiting-time distributions in terms of intervisit-time distributions. Next, we use these expressions to derive the asymptotic waiting-time distributions under heavy-traffic assumptions, i.e. when the system tends to saturate. The results show that in all cases the asymptotic waiting-time distribution at queue i is fully characterized and of the form ΓΘi with Γ and Θi independent, and where Γ is gamma distributed with known parameters (and the same for all scheduling policies). We derive the distribution of the random variable 0, which explicitly expresses the impact of the local service order on the asymptotic waiting-time distribution. The results provide new fundamental insight into the impact of the local scheduling policy on the performance of a general class of polling models. The asymptotic results suggest simple closed-form approximations for the complete waiting-time distributions for stable systems with arbitrary load values. [ABSTRACT FROM AUTHOR]

Objective: Up to 40% of breast cancer survivors develop lymphedema, a chronic and sometimes disabling condition that manifests as abnormal swelling of the effected arm or hand or upper chest areas. Although the effects of lymphedema on quality of life have been well established, less well documented are the sexual experiences of breast cancer survivors with lymphedema. This study is the first to compare the sexual experiences of women with (n = 243) and without breast cancer-related lymphedema (n = 109). Methods: A mixed-method design was used to explore both quantitatively and qualitatively the impact of lymphedema on participants' sexual experiences. Results: Participants with breast cancer-related lymphedema reported struggles with compression garments and sexual intimacy, negative feelings involving the breast and arm, and feelings of decreased sexual desire. Conclusions: Recommendations for healthcare professionals, social workers, and marriage and family therapists are offered with the aim of assisting women with breast cancer-related lymphedema and their sexual partners. [ABSTRACT FROM AUTHOR]

Breast cancer-related lymphedema is a syndrome of abnormal swelling coupled with multiple symptoms resulting from obstruction or disruption of the lymphatic system associated with cancer treatment. Research has demonstrated that with increased number of symptoms reported, breast cancer survivors' limb volume increased. Lymphedema symptoms in the affected limb may indicate a latent stage of lymphedema in which changes cannot be detected by objective measures. The latent stage of lymphedema may exist months or years before overt swelling occurs. Symptom report may play an important role in detecting lymphedema in clinical practice. The purposes of this study were to: 1) examine the validity, sensitivity, and specificity of symptoms for detecting breast cancer-related lymphedema and 2) determine the best clinical cutoff point for the count of symptoms that maximized the sum of sensitivity and specificity. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Lymphedema symptoms were assessed using a reliable and valid instrument. Validity, sensitivity, and specificity were evaluated using logistic regression, analysis of variance, and areas under receiver operating characteristic curves. Count of lymphedema symptoms was able to differentiate healthy adults from breast cancer survivors with lymphedema and those at risk for lymphedema. A diagnostic cutoff of three symptoms discriminated breast cancer survivors with lymphedema from healthy women with a sensitivity of 94% and a specificity of 97% (area under the curve =0.98). A diagnostic cutoff of nine symptoms discriminated at-risk survivors from survivors with lymphedema with a sensitivity of 64% and a specificity of 80% (area under the curve =0.72). In the absence of objective measurements capable of detecting latent stages of lymphedema, count of symptoms may be a cost-effective initial screening tool for detecting lymphedema. [ABSTRACT FROM AUTHOR]

Many breast cancer survivors have coexistent chronic diseases or comorbidities at the time of their cancer diagnosis. The purpose of the study was to evaluate the association of comorbidities on breast cancer survivors' quality of life. A prospective design was used to recruit 140 women before cancer surgery, 134 women completed the study. Comorbidities were assessed using self-report and verified by medical record review and the Charlson Comorbidity Index (CCI) before and 12-month after cancer surgery. Quality of life was evaluated using Short-Form Health Survey (SF-36 v2). Descriptive statistics, chi-square tests, t-tests, Fisher's exact test, and correlations were performed for data analysis. A total of 28 comorbidities were identified. Among the 134 patients, 73.8% had at least one of the comorbidities, 54.7% had 2-4, and only 7.4% had 5-8. Comorbidities did not change at 12 months after surgery. Numbers of comorbidities by patients' self-report and weighted categorization of comorbidities by CCI had a similar negative correlation with overall quality of life scores as well as domains of general health, physical functioning, bodily pain, and vitality. Comorbidities, specifically hypertension, arthritis, and diabetes, were associated with poorer quality of life in multiple domains among breast cancer survivors. Future research should consider the combined influence of comorbidity and cancer on patients' quality of life. [ABSTRACT FROM AUTHOR]

Obesity is one of the risk factors for developing lymphedema following breast cancer treatment. We prospectively enrolled 140 women and followed the participants for 12 months after surgery to investigate patterns of obesity and lymph fluid level in the first year of cancer treatment. Electrical bioimpedance devices were used to measure weight, BMI, and percent of body fat as well as lymph fluid level. General instructions were given to the participants on maintaining pre-surgery weight. Among the 140 participants, 136 completed the study with 2.9% attrition. More than 60% of the participants were obese (30.8%) or overweight (32.4%), while only two participants were underweight and about 35% had normal weight. This pattern of obesity and overweight was consistent at 4-8 weeks and 12 months post-surgery. At 12 months post-surgery, the majority of the women (72.1%) maintained pre-surgery weight and 15.4% had >5% weight loss; 12.5% of the women increase >5% of their weight. Significantly more patients in the obesity group had lymphedema defined by L-Dex ratio >7.1 than those in the normal/underweight and overweight group at pre-surgery and 4-8 weeks post-surgery. There was a trend of more patients in the obesity group had L-Dex ratio >7.1 at 12 months post-surgery. Obesity and overweight remain among women at the time of cancer diagnosis and the patterns of obesity and overweight continue during the first year of treatment. General instructions on having nutrition-balanced and portion-appropriate diet and physical activities daily or weekly can be effective to maintain pre-surgery weight. [ABSTRACT FROM AUTHOR]