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Research summary Policy implications This study provides a rigorous assessment of the public safety benefits of pretrial detention by estimating the criminogenic and punitive effects of spending at least 1 week in pretrial detention across three jail systems in two states. We use a doubly robust difference‐in‐differences design to show that pretrial detention increases the odds for someone to miss a court appearance or be arrested by roughly 50% and increases the odds of convictions by 36%. This evidence was support by a series of supplemental analyses demonstrating that spending more than 1 day and spending more than 3 days in pretrial detention increased the odds of negative pretrial outcomes compared to someone who was booked and released from jail. The findings of this study provide evidence that pretrial detention can be counterproductive to public safety in that it leads to increased likelihood that individuals will miss court and be arrested for new crimes.Jails are a unique criminal justice contact point because they hold individuals at different stages of case processing, including individuals awaiting trial, and those serving shorter sentences or waiting to be transferred to prison. Pretrial release is arguably one of the most consequential decisions in case processing for an individual. Combining our findings with the punitive and collateral effects of time spent in pretrial detention signals a need for policies to identify effective methods of release that maximize liberty, safety, and equity and minimize the criminogenic effects of pretrial detention. Jails are inhabited with pretrial detainees, detention makes outcomes worse for these detainees, and detention does not deliver on public safety as intended. We argue that a more limited and targeted use of pretrial detention is needed and more research attention on alternatives to pretrial detention. [ABSTRACT FROM AUTHOR]

We study the rank of the adjacency matrix A$$ A $$ of a random Erdős‐Rényi graph G∼픾(n,p). It is well known that when p=(log(n)−ω(1))/n$$ p=\left(\log (n)-\omega (1)\right)/n $$, with high probability, A$$ A $$ is singular. We prove that when p=ω(1/n)$$ p=\omega \left(1/n\right) $$, with high probability, the corank of A$$ A $$ is equal to the number of isolated vertices remaining in G$$ G $$ after the Karp‐Sipser leaf‐removal process, which removes vertices of degree one and their unique neighbor. We prove a similar result for the random matrix B$$ B $$, where all entries are independent Bernoulli random variables with parameter p$$ p $$. Namely, we show that if H$$ H $$ is the bipartite graph with bi‐adjacency matrix B$$ B $$, then the corank of B$$ B $$ is with high probability equal to the max of the number of left isolated vertices and the number of right isolated vertices remaining after the Karp‐Sipser leaf‐removal process on H$$ H $$. Additionally, we show that with high probability, the k$$ k $$‐core of 픾(n,p) is full rank for any k≥3$$ k\ge 3 $$ and p=ω(1/n)$$ p=\omega \left(1/n\right) $$. This partially resolves a conjecture of Van Vu for p=ω(1/n)$$ p=\omega \left(1/n\right) $$. Finally, we give an application of the techniques in this paper to gradient coding, a problem in distributed computing. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS: Genome‐wide association meta‐analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS: AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION: AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights: It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated.Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms.Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not.Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations. [ABSTRACT FROM AUTHOR]

Background: Enthusiasm for precision oncology may obscure the psychosocial and ethical considerations associated with the implementation of tumor genetic sequencing. Methods: Patients with advanced cancer undergoing tumor‐only genetic sequencing in the National Cancer Institute Molecular Analysis for Therapy Choice (MATCH) trial were randomized to a web‐based genetic education intervention or usual care. The primary outcomes were knowledge, anxiety, depression, and cancer‐specific distress collected at baseline (T0), posteducation (T1) and after results (T2). Two‐sided, 2‐sample t tests and univariate and multivariable generalized linear models were used. Results: Five hundred ninety‐four patients (80% from NCI Community Oncology Research Program sites) were randomized to the web intervention (n = 293) or usual care (n = 301) before the receipt of results. Patients in the intervention arm had greater increases in knowledge (P for T1‐T0 <.0001; P for T2‐T0 =.003), but there were no significant differences in distress outcomes. In unadjusted moderator analyses, there was a decrease in cancer‐specific distress among women (T0‐T1) in the intervention arm but not among men. Patients with lower health literacy in the intervention arm had greater increases in cancer‐specific distress and less decline in general anxiety (T0‐T1) and greater increases in depression (T0‐T2) in comparison with those receiving usual care. Conclusions: Web‐based genetic education before tumor‐only sequencing results increases patient understanding and reduces distress in women. Refinements to the intervention could benefit low‐literacy groups and men. In the Communication and Education in Tumor Profiling (COMET) study, patients with advanced cancer undergoing tumor genetic sequencing in the National Cancer Institute Molecular Analysis for Therapy Choice (MATCH) trial have been randomized to a web‐based genetic education intervention or usual care. Web‐based genetic education has resulted in increased patient understanding and reduced distress in female patients with cancer. [ABSTRACT FROM AUTHOR]

Background: Obesity is a chronic, relapsing, and progressive disease; it is associated with poor health‐related quality of life (HRQOL) in survivors of breast cancer. Methods: In this 2 × 2 factorial trial, 351 survivors of breast cancer with overweight or obesity were randomized to 1 of 4 treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. HRQOL end points were measured at baseline and at week 52 using the 36‐Item Medical Outcomes Survey‐Short Form (SF‐36). Repeated measures analysis of covariance quantified the estimated treatment difference (ETD). Results: At baseline, participants had a mean (SD) age of 59.4 years (8.7), body mass index of 34.0 kg/m2 (5.9), and 71 participants (20.2%) self‐reported fair or poor general health. After 52 weeks, compared with control, the exercise plus diet improved the physical health summary score (ETD: 5.39; 95% CI, 0.55‐10.22); exercise alone (ETD: –1.91; 95% CI, –6.60 to 2.79) and diet alone (ETD: 3.16; 95% CI, –1.52 to 7.83) did not change the physical health summary score. Compared with control, exercise alone (ETD: –0.27; 95% CI, –6.60 to 2.79), diet alone (ETD: 3.25; 95% CI, –1.41 to 7.91), and the exercise plus diet (ETD: 1.75; 95% CI, –2.90 to 6.39) did not change the mental health summary score. Exercise alone did not impact any HRQOL subscale; diet alone improved the vitality subscale; exercise plus diet improved the physical functioning, role—physical and vitality subscales. Conclusion: In survivors of breast cancer with overweight or obesity, exercise plus diet improved select HRQOL end points at week 52. Obesity is associated with poor health‐related quality of life in survivors of cancer. In survivors of breast cancer with overweight or obesity, exercise plus diet improved select health‐related quality of life end points at week 52. [ABSTRACT FROM AUTHOR]

Background: Given excellent survival outcomes in breast cancer, there is interest in de‐escalating the amount of chemotherapy delivered to patients. This approach may be of even greater importance in the setting of the COVID‐19 pandemic. Methods: This concurrent mixed methods study included (1) interviews with patients and patient advocates and (2) a cross‐sectional survey of women with breast cancer served by a charitable nonprofit organization. Questions evaluated interest in de‐escalation trial participation, perceived barriers/facilitators to participation, and language describing de‐escalation. Results: Sixteen patient advocates and 24 patients were interviewed. Key barriers to de‐escalation included fear of recurrence, worry about decision regret, lack of clinical trial interest, and dislike for focus on less treatment. Facilitators included trust in physician recommendation, toxicity avoidance, monitoring for progression, perception of good prognosis, and impact on daily life. Participants reported that the COVID‐19 pandemic made them more likely to avoid chemotherapy if possible. Of 91 survey respondents, many (43%) patients would have been unwilling to participation in a de‐escalation clinical trial. The most commonly reported barrier to participation was fear of recurrence (85%). Few patients (19%) considered clinical trials themselves as a barrier to de‐escalation trial participation. The most popular terminology describing chemotherapy de‐escalation was "lowest effective chemotherapy dose" (53%); no patients preferred the term "de‐escalation." Conclusions: Fear of recurrence is a common concern among breast cancer survivors and patient advocates, contributing to resistance to de‐escalation clinical trial participation. Additional research is needed to understand how to engage patients in de‐escalation trials. [ABSTRACT FROM AUTHOR]

Criminal justice agencies increasingly use community engagement practices in efforts to improve public safety and garner legitimacy. While crime rates can be measured, improved legitimacy is harder to gauge. This article provides a framework to assess the influence of community engagement practices in the criminal justice system on legitimacy in three areas: authenticity, coherence in structure, and shifts in power dynamics. We explore each component through case studies of community policing, consent decrees, and community courts, respectively. We propose that this framework could be used to assess or build the capacity of community engagement to repair relationships with marginalised communities. [ABSTRACT FROM AUTHOR]

Research Summary: We assess the predictive validity and differential prediction by race of one pretrial risk assessment, the Public Safety Assessment (PSA). The PSA was developed with support from the Laura and John Arnold Foundation (LJAF) to reduce the burden placed on vulnerable populations at the front end of the criminal justice system. The growing and disparate use of incarceration is one of the most pressing social issues facing the United States. The implementation of risk assessments has provided fuel for both sides of the reform debate with proponents arguing that the use of these assessments offers a policy mechanism to alleviate populations and bias. Risk assessment critics, however, argue that the use of the assessments exacerbates bias and does not improve decision‐making. By examining a statewide data set from Kentucky (N = 164,597), we found the PSA to have predictive validity measures in line with what are generally accepted within the criminal justice field. The differences we found indicate the PSA scores for failure to appear (FTA) are moderated by race, but these differences do not lead to disparate impact. Policy Implications: We point to data limitations and the need for localized risk assessment studies, and we emphasize that risk assessments are decision‐making tools that require ongoing refinement. Risk assessment developers, opponents, and proponents would do better to focus on the reality of risk assessments as probabilistic models. The results of these assessments cannot predict with certainty, and they are not inherently biased. Rather, criminologists and policy makers need to understand the uncertainty that comes with any predictive model. [ABSTRACT FROM AUTHOR]

Background: Preterm delivery and current nutrition strategies result in deficiencies of critical long-chain fatty acids (FAs) and lipophilic nutrients, increasing the risk of preterm morbidities. We sought to determine the efficacy of preventing postnatal deficits in FAs and lipophilic nutrients using an enteral concentrated lipid supplement in preterm piglets.Methods: Preterm piglets were fed a baseline diet devoid of arachidonic acid (AA) and docosahexaenoic acid (DHA) and randomized to enteral supplementation as follows: (1) Intralipid (IL), (2) complex lipid supplement 1 (CLS1) with an AA:DHA ratio of 0.25, or (3) CLS2 with an AA:DHA ratio of 1.2. On day 8, plasma and tissue levels of FAs and lipophilic nutrients were measured and ileum histology performed.Results: Plasma DHA levels decreased in the IL group by day 2. In contrast, DHA increased by day 2 compared with birth levels in both CLS1 and CLS2 groups. The IL and CLS1 groups demonstrated a continued decline in AA levels during the 8-day protocol, whereas AA levels in the CLS2 group on day 8 were comparable to birth levels. Preserving AA levels in the CLS2 group was associated with greater ileal villus height and muscular layer thickness. Lipophilic nutrients were effectively absorbed in plasma and tissues.Conclusions: Enteral administration of CLS1 and CLS2 demonstrated similar increases in DHA levels compared with birth levels. Only CLS2 maintained AA birth levels. Providing a concentrated complex lipid emulsion with an AA:DHA ratio > 1 is important in preventing postnatal AA deficits. [ABSTRACT FROM AUTHOR]

Background: Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership. Methods: Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class. Results: Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain. Conclusions: Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long‐term risk of heart failure, particularly in those with modest LVEF declines. Modest declines in left ventricular ejection fraction (LVEF) in patients with breast cancer who are treated with cardiotoxic cancer therapy are accompanied by an increased incidence of biochemical and functional abnormalities. This suggests that declines in LVEF that do not reach the conventional thresholds used for the diagnosis of cardiotoxicity could be more clinically important than previously understood. [ABSTRACT FROM AUTHOR]

Social media communication among clinical trial participants has the potential to pose risks to their safety and to trial integrity. The Social Media ADEPT framework may help mitigate that potential by encouraging investigators and patient partners to work together to Assess social media risks, Design studies to minimize those risks, Educate participants, Preempt problems, and Take additional steps as needed, such as intervening when problems arise. [ABSTRACT FROM AUTHOR]

Research Summary: In the program implemented in the Honest Opportunity Probation with Enforcement Demonstration Field Experiment (HOPE DFE), the following approach is taken: close monitoring; frequent drug testing; readily available substance abuse treatment; and swift, certain, and fair sanctioning to deter probationers from violating supervision conditions. We assessed in this study the costs and outcomes of the demonstration program across four jurisdictions, using 24 months of data from 625 probationers randomly assigned to probation as usual (PAU) or HOPE DFE. Our results reveal that the HOPE DFE group incurred more criminal justice costs than the PAU group over the observation period. Policy Implications: Our study results further demonstrate that HOPE in the DFE is associated with higher rates of incarceration and residential treatment, leading to an increase in total costs when compared with PAU. Jurisdictions choosing to implement programs like HOPE to hold probationers accountable would need additional resources from the criminal justice system to support the program. [ABSTRACT FROM AUTHOR]

Background: Black women are more likely to experience adverse effects from cancer treatment such as lymphedema. Thus, black women may particularly benefit from research regarding interventions to improve lymphedema. Herein, the authors report the challenges and strategies related to the recruitment of minority survivors of breast cancer and to the recruitment of survivors of breast cancer with lymphedema into the Women In Steady Exercise Research (WISER) Survivor Clinical Trial.Methods: Subjects for this community-based trial were recruited from the Philadelphia area through active (mailings) and passive (printed materials and Web site) recruitment strategies. In addition, education sessions coordinated through partner hospitals in communities with a predominantly minority population were conducted to increase awareness of lymphedema in survivors of breast cancer. Women who were interested in the study were screened for lymphedema via telephone questionnaire and invited to see a study-related certified lymphedema therapist to confirm the presence of lymphedema.Results: Screening was conducted among 2295 women: 628 were eligible, 450 consented, and 351 were randomized. Minority women comprised 38% of the study population. Letters to women on state and hospital registries resulted in a 0.4% randomization rate; education sessions yielded a 10% randomization rate. The authors observed that approximately 23.6% of the study sample had no previous diagnosis of lymphedema.Conclusions: The WISER Survivor Clinical Trial faced multiple recruitment challenges and used unique strategies to successfully enroll minority survivors of breast cancer into a lifestyle intervention. Cancer 2018;124:95-104. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Neutropenia is the most commonly reported hematologic toxicity following treatment with palbociclib, a cyclin-dependent kinase 4/6 inhibitor approved for metastatic breast cancer. Using data from 185 advanced cancer patients receiving palbociclib in 3 clinical trials, a pharmacokinetic-pharmacodynamic model was developed to describe the time course of absolute neutrophil count (ANC) and quantify the exposure-response relationship for neutropenia. These analyses help in understanding neutropenia associated with palbociclib and its comparison with chemotherapy-induced neutropenia. In the model, palbociclib plasma concentration was related to its antiproliferative effect on precursor cells through drug-related parameters (ie, maximum estimated drug effect and concentration corresponding to 50% of the maximum effect), and neutrophil physiology was mimicked through system-related parameters (ie, mean transit time, baseline ANC, and feedback parameter). Sex and baseline albumin level were significant covariates for baseline ANC. It was demonstrated by different model evaluation approaches (eg, prediction-corrected visual predictive check and standardized visual predictive check) that the final model adequately described longitudinal ANC with good predictive capability. The established model suggested that higher palbociclib exposure was associated with lower longitudinal neutrophil counts. The ANC nadir was reached approximately 21 days after palbociclib treatment initiation. Consistent with their mechanisms of action, neutropenia associated with palbociclib (cytostatic) was rapidly reversible and noncumulative, with a notably weaker antiproliferative effect on precursor cells relative to chemotherapies (cytotoxic). This pharmacokinetic-pharmacodynamic model aids in predicting neutropenia and optimizing dosing for future palbociclib trials with different dosing regimen combinations. [ABSTRACT FROM AUTHOR]

Background Next-generation sequencing ( NGS) of surgically resected solid tumor samples has become integral to personalized medicine approaches for cancer treatment and monitoring. Liquid biopsies, or the enrichment and characterization of circulating tumor cells ( CTCs) from blood, can provide noninvasive detection of evolving tumor mutations to improve cancer patient care. However, the application of solid tumor NGS approaches to circulating tumor samples has been hampered by the low-input DNA available from rare CTCs. Moreover, whole genome amplification ( WGA) approaches used to generate sufficient input DNA are often incompatible with blood collection tube preservatives used to facilitate clinical sample batching. Methods To address this, we have developed a novel approach combining tumor cell isolation from preserved blood with Repli-G WGA and Illumina TruSeq Amplicon Cancer Panel-based NGS. We purified cell pools ranging from 10 to 1000 cells from three different cell lines, and quantitatively demonstrate comparable quality of DNA extracted from preserved versus unpreserved samples. Results Preservation and WGA were compatible with the generation of high-quality libraries. Known point mutations and gene amplification were detected for libraries that had been prepared from amplified DNA from preserved blood. Conclusion These spiking experiments provide proof of concept of a clinically applicable workflow for real-time monitoring of patient tumor using noninvasive liquid biopsies. [ABSTRACT FROM AUTHOR]

Researchers and clinicians are increasingly recognizing the value of patient-reported outcome (PRO) data to better characterize people's health and experiences with illness and care. Considering the rising prevalence of cancer in adults aged 65 and older, PRO data are particularly relevant for older adults with cancer, who often require complex cancer care and have additional comorbid conditions. A data linkage between the Surveillance Epidemiology and End Results (SEER) cancer registry and the Medicare Health Outcomes Survey (MHOS) was created through a partnership between the National Cancer Institute and the Centers for Medicare and Medicaid Services that created the opportunity to examine PROs in Medicare Advantage enrollees with and without cancer. The December 2013 linkage of SEER-MHOS data included the linked data for 12 cohorts, bringing the number of individuals in the linked data set to 95,723 with cancer and 1,510,127 without. This article reviews the features of the resource and provides information on some descriptive characteristics of the individuals in the data set (health-related quality of life, body mass index, fall risk management, number of unhealthy days in the past month). Individuals without (n = 258,108) and with (n = 3,440) cancer (1,311 men with prostate cancer, 982 women with breast cancer, 689 with colorectal cancer, 458 with lung cancer) were included in the current descriptive analysis. Given increasing longevity, advances in effective therapies and earlier detection, and population growth, the number of individuals aged 65 and older with cancer is expected to reach more than 12 million by 2020. SEER-MHOS provides population-level, self-reported, cancer registry-linked data for person-centered surveillance research on this growing population. [ABSTRACT FROM AUTHOR]

Purpose To evaluate DRAMMS, an attribute-based deformable registration algorithm, compared to other intensity-based algorithms, for longitudinal breast MRI registration, and to show its applicability in quantifying tumor changes over the course of neoadjuvant chemotherapy. Methods Breast magnetic resonance images from 14 women undergoing neoadjuvant chemotherapy were analyzed. The accuracy of DRAMMS versus five intensity-based deformable registration methods was evaluated based on 2,380 landmarks independently annotated by two experts, for the entire image volume, different image subregions, and patient subgroups. The registration method with the smallest landmark error was used to quantify tumor changes, by calculating the Jacobian determinant maps of the registration deformation. Results DRAMMS had the smallest landmark errors (6.05 ± 4.86 mm), followed by the intensity-based methods CC-FFD (8.07 ± 3.86 mm), NMI-FFD (8.21 ± 3.81 mm), SSD-FFD (9.46 ± 4.55 mm), Demons (10.76 ± 6.01 mm), and Diffeomorphic Demons (10.82 ± 6.11 mm). Results show that registration accuracy also depends on tumor versus normal tissue regions and different patient subgroups. Conclusions The DRAMMS deformable registration method, driven by attribute-matching and mutual-saliency, can register longitudinal breast magnetic resonance images with a higher accuracy than several intensity-matching methods included in this article. As such, it could be valuable for more accurately quantifying heterogeneous tumor changes as a marker of response to treatment. Magn Reson Med 73:2343-2356, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

BACKGROUND Although fatigue, sleep disturbance, depression, and anxiety are associated with pain in breast cancer patients, it is unknown whether acupuncture can decrease these comorbid symptoms in cancer patients with pain. The objective of this study was to evaluate the effect of electroacupuncture (EA) on fatigue, sleep, and psychological distress in breast cancer survivors who experience joint pain related to aromatase inhibitors (AIs). METHODS The authors performed a randomized controlled trial of an 8-week course of EA compared with a waitlist control (WLC) group and a sham acupuncture (SA) group in postmenopausal women with breast cancer who self-reported joint pain attributable to AIs. Fatigue, sleep disturbance, anxiety, and depression were measured using the Brief Fatigue Inventory (BFI), the Pittsburgh Sleep Quality Index (PSQI), and the Hospital Anxiety and Depression Scale (HADS). The effects of EA and SA versus WLC on these outcomes were evaluated using mixed-effects models. RESULTS Of the 67 randomly assigned patients, baseline pain interference was associated with fatigue (Pearson correlation coefficient [ r]=0.75; P < .001), sleep disturbance ( r=0.38; P=.0026), and depression ( r=0.58; P < .001). Compared with the WLC condition, EA produced significant improvements in fatigue ( P=.0095), anxiety ( P=.044), and depression ( P=.015) and a nonsignificant improvement in sleep disturbance ( P=.058) during the 12-week intervention and follow-up period. In contrast, SA did not produce significant reductions in fatigue or anxiety symptoms but did produce a significant improvement in depression compared with the WLC condition ( P=.0088). CONCLUSIONS Compared with usual care, EA produced significant improvements in fatigue, anxiety, and depression; whereas SA improved only depression in women experiencing AI-related arthralgia. Cancer 2014;120:3744-3751. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Endocrine measures of ovarian reserve before breast cancer treatment may predict postchemotherapy ovarian function, providing prognostic information at the time of cancer diagnosis. The objectives of this study were 1) to determine whether prechemotherapy levels of antimullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B (inhB) are associated with the return of ovarian function after chemotherapy and 2) to generate a prognostic score for ovarian recovery in young women with breast cancer. METHODS A prospective cohort study recruited 109 participants (median age, 39 years; age range, 23-45 years) before chemotherapy from 2 breast clinics and followed them longitudinally. By using time-to-event analysis, the authors tested the association between prechemotherapy AMH, FSH, and inhB levels and the time to return of ovarian function, as measured by menstrual pattern. RESULTS After a median follow-up of 163 days (range, 4-1009 days) after chemotherapy, 62 participants (57%) experienced return of ovarian function. In adjusted analyses, AMH levels >0.7 ng/mL (hazard ratio, 2.9; 95% confidence interval, 1.5-5.6) and FSH levels ≤10 IU/L (hazard ratio, 4.7; 95% confidence interval, 1.3-16.8) were associated with a shorter time to ovarian recovery, whereas inhB levels were not related. A prognostic score based on age <40 years, AMH >0.7 ng/mL, and body mass index ≥25 kg/m2 was used to estimate the timing of recovery. CONCLUSIONS In reproductive-aged women with newly diagnosed breast cancer, prechemotherapy AMH and FSH levels were associated with the return of ovarian function, independent of age. A novel prognostic score incorporating AMH, age, and body size was capable of estimating the time to ovarian recovery. Pending validation, these data support using prechemotherapy ovarian reserve measures, particularly AMH, to prospectively counsel young patients on future ovarian function. Because ovarian function is not equivalent to fertility, follow-up studies on predicting fertility are needed. Cancer 2014;120:3691-3698. © 2014 American Cancer Society. [ABSTRACT FROM AUTHOR]

An essay is presented concerning how electronic monitoring can be incorporated within a punishment approach that is effective and humane. Topics discussed include contextual differences between the Scandinavian and U.S. systems, operation of Scandinavian prisons under the philosophy of normalization, and two National Institute of Justice studies that showed positive outcomes for electronic supervision.

Laboratory studies suggest that vitamin D (vitD) enhances chemotherapy-induced cell death. The objective of this study was to determine whether pretreatment vitD levels were associated with response to neoadjuvant chemotherapy ( NACT) in women with breast cancer. Study patients ( n = 82) were enrolled on the I- SPY TRIAL, had HER2-negative tumors, and available pretreatment serum. VitD levels were measured via DiaSorin radioimmunoassay. The primary outcome was pathologic residual cancer burden ( RCB; dichotomized 0/1 vs. 2/3). Secondary outcomes included biomarkers of proliferation, differentiation, and apoptosis (Ki67, grade, Bcl2, respectively) and 3-year relapse-free survival ( RFS). Mean and median vitD values were 22.7 ng/mL ( SD 11.9) and 23.1 ng/mL, respectively; 72% of patients had levels deemed 'insufficient' (<30 ng/mL) by the Institute of Medicine ( IOM). VitD level was not associated with attaining RCB 0/1 after NACT (univariate odds ratio [ OR], 1.01; 95% CI, 0.96-1.05) even after adjustment for hormone receptor status ( HR), grade, Ki67, or body mass index ( BMI). Lower vitD levels were associated with higher tumor Ki67 adjusting for race ( OR, 0.95; 95% CI, 0.90-0.99). VitD level was not associated with 3-year RFS, either alone (hazard ratio [HzR], 0.98; 95% CI, 0.95-1.02) or after adjustment for HR, grade, Ki-67, BMI, or response. VitD insufficiency was common at the time of breast cancer diagnosis among women who were candidates for NACT and was associated with a more proliferative phenotype. However, vitD levels had no impact on tumor response to NACT or short-term prognosis. [ABSTRACT FROM AUTHOR]

R4279 --> 527.6 --> Aims & Hypothesis: The palatine tonsils are aggregates of lymphoid tissue in the lateral oropharynx. In children, tonsillar enlargement can lead to upper airway obstruction and sleep‐disordered breathing (SDB). The reason for tonsillar enlargement in some children, and not others is unknown. We have investigated the role of the tonsillar microbiota in tonsillar enlargement. The role of bacterial biofilms in RT and SDB was investigated through comparisons of tonsil histopathology, mixed‐species biofilm's microbiota composition and biofilm phenotypes. We hypothesized that the SDB tonsillar phenotype has distinct biofilm forming bacterial communities driving tonsillar hyperplasia compared to recurrent tonsillitis. Methods: Tonsils were acquired via tonsillectomy from children with RT or SDB. Tonsils were stained to assess florid reactive lymphoid hyperplasia (FRLH). In situ microbiota characterization was assessed by 16S rRNA gene sequencing and overall bacterial biomass was assessed by 16S qPCR. Tonsillar bacteria were extracted and grown in BHI media for in vitro assays. Oral microbiota biofilms were characterized using the Calgary Biofilm Device and "O'Toole" assay. Biofilm biomass was assessed by spectrophotometry using crystal violet staining. Bacterial adhesion/invasion assays were performed by infecting pharyngeal carcinoma cell lines Det‐562 with tonsil microbiota from RT and SDB groups. Immune profile of Det‐562 cells infected with RT and SDB microbiota (t=3 hours) was assessed by cytokine multiplex analysis. Results: Histopathological analysis showed higher FRLH of the enlarged lymph node in the SDB group compared to RT group. Microbiota analysis has shown that the tonsil's microbiota composition and bacterial biomass did not significantly differ between tonsils that were taken out due to SDB and those taken out for recurrent tonsillitis. Calgary Biofilm Device biofilm assays indicated that the SDB multi‐species biofilms have higher biomass compared to RT biofilms. Microbiota from SDB group were more adhesive/invasive to Det‐562 cells compared to RT bacteria after 3 hours incubation. Cytokine profiling showed increased expression of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), pro‐inflammatory cytokines IL‐1β, IL‐2, IL‐12 and interferon gamma (IFNγ) in Det‐562 cells exposed to SDB microbiota compared to RT. Conclusions: Our results indicate that SDB and RT tonsils have distinct histopathological signatures. In situ tonsillar microbiota composition and bacterial load did not differ between SDB and RT groups. In vitro assays showed that SDB tonsils exhibit increases in both multi‐species biofilm mass and bacterial adhesion/invasion to epithelial surfaces. These results also suggest that SDB bacterial biofilms lead to greater inflammation of the tonsils, confirmed by the elevated levels of FRLH and increased expression of pro‐inflammatory mediators. This study sheds light on the role pathobionts released from dysbiotic oral microbiota biofilms in the development of tonsillitis. [ABSTRACT FROM AUTHOR]

An essay is presented about the use of predictive tools to prevent drunk driving. The authors list some basic comments about predictive tools that may help them to understand efforts to develop risk-assessment instruments to identify persistent drunk drivers. They conclude that predicting driving under influence (DUI) recidivism is a data problem that has implications for criminal justice budgets, officer time and offender outcomes.

BACKGROUND: A key purpose of routine distress screening is to ensure that cancer patients receive appropriate mental health care. Most studies validating screening instruments overestimate the effectiveness of screening by not differentiating between patients with untreated disorders and patients who are already being treated. This study adopts the novel strategy of evaluating the effectiveness of screening after correcting for disorder for which treatment is already being provided. METHODS: A total of 437 recently diagnosed breast cancer patients received in-clinic distress screening and telephone-based psychiatric interviews. Analyses were conducted using receipt of psychotropic medication for mental health difficulties in the context of a psychiatric disorder as a proxy for identification and treatment. RESULTS: Rates of elevated distress (33%), major depressive disorder (8%), minor depression (6%), dysthymia (2%), or generalized anxiety disorder (3%) were similar to those in other samples. Thirty-six percent of patients received psychotropic medication around the time of cancer diagnosis, including 64% of those with a current psychiatric diagnosis. Although 39% of patients with elevated distress had a psychiatric disorder, the positive predictive value of screening fell to 15% for an untreated psychiatric disorder and 6% had untreated depression. CONCLUSION: Given the high rates of existing treatment, screening may not be efficient for identifying untreated disorder. Almost two-thirds of patients with treated disorders remain symptomatic. Use of symptom scales might reasonably be expanded to surveillance of treatment response or ruling out disorder. Substantial resources would likely be required to coordinate or manage psychiatric care among patients, as would a willingness to intervene in existing relationships with other providers. Cancer 2011. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background A novel nutritional formula (NNF) enriched in eicosapentaenoic (EPA) and γ-linolenic fatty acids and antioxidants reduces airway inflammation and improves clinical outcomes in critically ill patients, but NNF has not been evaluated in chronic inflammatory diseases such as persistent asthma. Objective To evaluate the efficacy, compliance, and safety of NNF in asthmatic children. Methods Children, 6–14 years of age, with mild to moderate persistent asthma, on as needed albuterol alone, were randomized to receive daily NNF ( n=23) or control formula ( n=20) for 12 weeks, with multiple assessments of asthma control, spirometry, measures of airway inflammation, formula tolerance, and adverse events. Results Daily consumption of either NNF or a control formula showed improvement in asthma-free days over time ( P=0.04) but there was no difference between groups. However, the NNF group had lower exhaled nitric oxide levels compared with the control group at weeks 4, 8, and 12 ( P<0.05). An overall group difference in log FEV1 PC20 ( P=0.05) was found in favour of the NNF group as well. Significantly higher levels of EPA in plasma ( P<0.01) and peripheral blood mononuclear cell (PBMC) ( P<0.01) phospholipids in the NNF group compared with control group within 2 weeks indicated good adherence with daily NNF intake. There were no differences in adverse events for NNF vs. control after 12 weeks. Conclusions Both NNF and control groups demonstrated improvement in asthma-free days. NNF-treated group had reduced biomarkers of disease activity. Rapid PBMC fatty acid composition changes reflected an anti-inflammatory profile. Dietary supplementation with NNF was safe and well tolerated (ClinicalTrials.gov number NCT01087710). Cite this as: R. Covar, M. Gleason, B. Macomber, L. Stewart, P. Szefler, K. Engelhardt, J. Murphy, A. Liu, S. Wood, S. DeMichele, E. W. Gelfand and S. J. Szefler, Clinical & Experimental Allergy, 2010 (40) 1163–1174. [ABSTRACT FROM AUTHOR]

Purpose: Computer aided detection (CAD) data analysis procedures are introduced and applied to derive composite diffuse optical tomography (DOT) signatures of malignancy in human breast tissue. In contrast to previous optical mammography analysis schemes, the new statistical approach utilizes optical property distributions across multiple subjects and across the many voxels of each subject. The methodology is tested in a population of 35 biopsy-confirmed malignant lesions. Methods: DOT CAD employs multiparameter, multivoxel, multisubject measurements to derive a simple function that transforms DOT images of tissue chromophores and scattering into a probability of malignancy tomogram. The formalism incorporates both intrasubject spatial heterogeneity and intersubject distributions of physiological properties derived from a population of cancer-containing breasts (the training set). A weighted combination of physiological parameters from the training set define a malignancy parameter (M), with the weighting factors optimized by logistic regression to separate training-set cancer voxels from training-set healthy voxels. The utility of M is examined, employing 3D DOT images from an additional subjects (the test set). Results: Initial results confirm that the automated technique can produce tomograms that distinguish healthy from malignant tissue. When compared to a gold standard tissue segmentation, this protocol produced an average true positive rate (sensitivity) of 89% and a true negative rate (specificity) of 94% using an empirically chosen probability threshold. Conclusions: This study suggests that the automated multisubject, multivoxel, multiparameter statistical analysis of diffuse optical data is potentially quite useful, producing tomograms that distinguish healthy from malignant tissue. This type of data analysis may also prove useful for suppression of image artifacts. [ABSTRACT FROM AUTHOR]

The article presents a study on the influence of breast cancer treatment in the antimullerain hormone (AMH) and inhibin B among cancer survivors. It states that the study was performed among 127 postchemotherapy breast cancer survivors from the Rena Rowan Breast Center of the University of Pennsylvania and compared them to normal controls from the Penn Ovarian Aging Study. It reveals that the AMH and inhibin B serve as biomarkers of postchemotherapy ovarian function.

The article examines various issues in the field of adult cancer survivorship, such as the increasing number of young adult survivors of childhood cancer, the translational research needed to promote care of cancer survivors, and the measures that must be taken by primary and specialty care providers in the management of the survivors. It discusses the evolution of care plan initiatives for cancer survivors. It also discusses the importance of survivorship phase of care in cancer care.

The article reports on the study that evaluates the perceived onset, characteristics and risk factors of aromatase inhibitors (AI)-related arthralgia (AIA) among breast cancer patients. It found that 47% of patients have attributed AI as a cause of their arthralgia, while 74% of patients have recognized the onset of AIA within three months of starting medication. It indicated that AIA began within the first three months of therapy in most patients.

The article presents a study which explores the relation between patient information seeking and awareness about novel targeted therapy (TT) for colon cancer. The authors investigated the therapy for the disorder among patients for whom therapy is approved and in patients for whom therapy is not approved by the U.S. Food and Drug Administration. The study found out that the information seeking by patients is linked to the adoption of TT for colon cancer.

Historically, the efficacy of probation and parole policies and practices have been judged by the general public, politicians, and many professional insiders by sensationalised crimes involving individuals sentenced to community supervision. The probation and parole profession has not established mechanisms to clearly articulate its public value; doing so would foster the development of policies and practices that derive more from empirical research evidence and sound theory than political faddism. The failure within the probation and parole profession to come to broad agreement regarding desired outcomes and to establish evidence-based and/or theoretically-sound professional principles has created a policy lacuna that is too often filled by elected officials who lack an understanding of the history, science, and philosophy of probation and parole. Probation and parole agencies should focus on producing publicly-valued results and disseminating easily-understood information that justifies their important niche within America's criminal justice system. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess whether an experimental nutritional formula (EXP) supports immune function in seniors living in long-term care facilities. DESIGN: Prospective, randomized, double-blind, controlled trial conducted September 2002 through January 2003. SETTING: North central Florida nursing homes. PARTICIPANTS: Subjects aged 65 and older (n=157). INTERVENTION: Subjects received 240 mL/d of EXP or standard liquid nutrition (CON) for 4 weeks before and 6 weeks after an influenza vaccination. MEASUREMENTS: Influenza vaccine antibody responses, immunophenotyping, lymphocyte activation, cytokines, and clinical measures (fever, number of prescribed antibiotics). RESULTS: Ninety-two subjects (n=40, CON; n=52, EXP) completed the study. Geometric mean antibody titers were similar between groups, yet the percentage of subjects with H1N1 antibody titers greater than 100 postvaccination was higher in the EXP group than in the CON group (43% vs 23%, P=.047). Similar trends were found for the percentage of subjects (intent to treat) with fourfold increases against the B/Hong Kong component (64% vs 46%, P=.09) or with H3N2 antibody titers of 40 or more (97% vs 89%, P=.06). EXP subjects had higher levels of influenza-activated lymphocytes (CD69+and CD25+). Cytokine production after mitogen activation was lower in EXP than CON subjects (interleukin (IL)-6: 20±3 vs 29±3 ng/mL, P=.045; IL-10: 310±60 vs 603±140 pg/mL, P=.06). Fewer EXP subjects were treated for fever (5% vs 16%, P=.02) or prescribed antibiotics (7 vs 11 new antibiotics/100 days of study, P=.06). CONCLUSION: Seniors consuming the EXP formula demonstrated enhanced immune function, indicated by increased influenza vaccine response and lymphocyte activation, less fever, and fewer newly prescribed antibiotics than those consuming a standard ready-to-drink nutritional supplement. [ABSTRACT FROM AUTHOR]

Previous research in rats and mice has suggested that γ-linolenic acid (GLA) derived from borage oil (BO: 23% GLA) may be an appropriate source for increasing levels of long-chain n−6 FA in the developing brain. Recently, transgenic technology has made available a highly enriched GLA seed oil from the canola plant (HGCO: 36% GLA). The first objective of this study was to compare the effects of diets containing equal levels of GLA (23%) from either BO or HGCO on reproduction, pup development, and pup brain FA composition in mice. The second objective was to compare the effects of the HGCO diluted to 23% GLA (GLA-23) with those of undiluted HGCO containing 36% GLA (GLA-36). The diets were fed to the dams prior to conception and throughout pregnancy and lactation, as well as to the pups after weaning. The behavioral development of the pups was measured 12 d after birth, and anxiety in the adult male offspring was assessed using the plus maze. The findings show that despite equivalent levels of GLA, GLA-23 differed from BO in that it reduced pup body weight and was associated with a slight increase in neonatal pup attrition. However, there were no significant effects on pup behavioral development or on performance in the plus maze. An increase in dietary GLA resulted in an increase in brain 20∶4n−6 and 22∶4n−6, with a corresponding decrease in 22∶6n−3. Again, despite their similar levels of GLA, these effects tended to be larger in GLA-23 than in BO. In comparison with GLA-23, GLA-36 had larger effects on growth and brain FA composition but no differences with respect to effects on reproduction and behavioral development. These findings suggest that the HGCO can be used as an alternative source of GLA. [ABSTRACT FROM AUTHOR]

We have utilized transgenic technology to develop a new source of γ-linolenic acid (GLA) using the canola plant as a host. The aim of the present study was to compare the growth and fatty acid metabolism in rats fed equal amounts of GLA obtained from the transgenic canola plant relative to GLA from the borage plant. Young male Sprague-Dawley rats ( n=10/group) were randomized and fed a purified AIN93G diet (10% lipid by weight) containing either a mixture of high GLA canola oil (HGCO) and corn oil or a control diet containing borage oil (BO) for 6 wk. GLA accounted for 23% of the triglyceride fatty acids in both diets. Growth and diet consumption were monitored every 2–3 d throughout the study. At study termination, the fatty acid composition of the liver and plasma phospholipids was analyzed by gas chromatography. The growth and diet consumption of the HGCO group were similar to the BO group. There were no adverse effects of either diet on the general health or appearance of the rats, or on the morphology of the major organs. There was no significant difference between the diet groups for total percentage of n−6 polyunsaturated fatty acids present in either the total or individual phospholipid fractions of liver or plasma. The relative percentage of GLA and its main metabolite, arachidonic acid, in each phospholipid fraction of liver or plasma were also similar between groups. The percentage of 18∶2n−6 in liver phosphatidylethanolamine and phosphatidylinositol/serine was higher ( P<0.05) and 22∶5n−6 was lower in the HGCO group than the BO group. This finding could be attributed to the higher 18∶3n−3 content in the HGCO diet than the BO diet. Results from this long-term feeding study of rats show for the first time that a diet containing transgenically modified canola oil was well-tolerated, and had similar biological effects, i.e., growth characteristics and hepatic metabolism of n−6 fatty acids, as a diet containing borage oil. [ABSTRACT FROM AUTHOR]

The suggestion of concentration dependent unloading as a necessary assumption for a closed-form mathematical expression of the Münch hypothesis of phloem transport (Goeschl et al., 1976) has been recently questioned (Ferrier & Christy, 1977). Also questioned was whether previous models, known to have one less equation than dependent variables, have produced erroneous or misleading results. A review of Münch's original concepts and recent comments by several researchers indicate that an equation describing the exit of solutes from sieve tubes is essential for consistency with the Münch hypothesis. Evidence is presented to show that previous mathematical predictions and interpretations regarding `runaway velocities' have resulted in part from mathematical inconsistencies and characteristics of the numerical solution procedures. Likewise, a proposal that different steady-state velocities and concentrations of transport at a given loading rate might be determined by `previous history' of the system can be explained on the basis of implied relationships hidden in models with insufficient equations. Finally it is concluded that concentration dependent unloading in models of the Münch hypothesis will not detract, but rather will contribute to their usefulness in experimental testing and other research regarding phloem transport. [ABSTRACT FROM AUTHOR]