Enhancing detection of labor violations in the agricultural sector: A multilevel generalized linear regression model of H-2A violation counts.

Agricultural workers are essential to the supply chain for our daily food, and yet, many face harmful work conditions, including garnished wages, and other labor violations. Workers on H-2A visas are particularly vulnerable due to the precarity of their immigration status being tied to their employer. Although worksite inspections are one mechanism to detect such violations, many labor violations affecting agricultural workers go undetected due to limited inspection resources. In this study, we identify multiple state and industry level factors that correlate with H-2A violations identified by the U.S. Department of Labor's Wage and Hour Division using a multilevel zero-inflated negative binomial model. We find that three state-level factors (average farm acreage size, the number of agricultural establishments with less than 20 employees, and higher poverty rates) are correlated with H-2A violations. These findings offer valuable insights into where H-2A violations are being detected at the state and industry levels.

Which Latinos Experience Bias Victimization? An Examination of Acculturation, Immigrant Status, and Socio-economic Status.

The present study examined factors that could be associated with bias victimization according to intergroup threat theory, namely socioeconomic status (SES), acculturation (Anglo orientation and Latino orientation), immigrant status, and their interactions. Self-identified Latino participants (N = 910) from three cities in the United States were queried about experiences with bias victimization, specifically hate crime and noncriminal bias victimization. Findings revealed that levels of bias victimization, hate crime, and noncriminal bias victimization were associated with SES, Anglo orientation, immigrant status, and their interactions, although in some unpredicted ways. Interactions among key variables helped clarify the roles of these factors in concert on bias victimization. The hate crimes against U.S.-born Latinos and the victimization risk associated with increasing Anglo orientations among immigrants contradicts predictions of intergroup threat theory. More nuanced analyses of social locations are needed to examine bias victimization.

Bias Crime and Victimization Among Latinx Adults: Formal and Informal Help Seeking.

Latinx adults have become increasingly vulnerable to bias motivated victimization. The impact of such incidents on Latinx communities is severely understudied, particularly concerning whether or not victims will seek help as a result of such events. Evidence within other victimization contexts demonstrate Latinx populations may be less likely to seek formal help from police, medical providers, and other formal authorities, relying instead on informal support networks such as family and friends. The current study sought to understand formal and informal help-seeking behavior among Latinx adults who experienced bias motivated victimization. The Understanding and Measuring Bias Victimization against Latinos study obtained rates of bias victimization and subsequent help-seeking behavior among Latinx adults who reported experiencing bias victimization (n = 315, 34.6% of full sample of 910). Those who experience bias victimization seek formal help at much lower rates than informal forms of support. Logistic regression analyses controlling the type of victimization demonstrated that participants who experienced a victimization constituting a hate crime were more likely to seek formal help compared to experiencing non-criminal bias events. Implications include addressing barriers to Latinx bias victims seeking forms of help, in addition to understanding the potential polyvictimization histories that predict why Latinx adults may decide to seek help.

Pregnancy-related claustrophobia.

A 35-year-old primigravida presented with significant anxiety symptoms at 26 weeks' gestation. Symptoms were preceded by a nightmare about her upcoming labour. She developed repetitive intrusive thoughts of being trapped emotionally and physically in her pregnancy. Her symptoms were suggestive of new-onset claustrophobia associated with pregnancy, which has not been previously reported on. Her symptoms ameliorated with a combination of cognitive-behavioural therapy and pharmacotherapy (sertraline and low dose quetiapine). The later stages of pregnancy were associated with minimal symptoms and the resolution of her subjective 'entrapment'. A subsequent pregnancy resulted in similar although less severe symptomatology. No postpartum anxiety symptoms were demonstrated on both occasions. Anxiety symptoms can adversely impact both the mother and fetus, and thus correct identification and management of pregnancy-related claustrophobia improved symptomatology and functioning and allowed for earlier detection and reduced symptomatology in a subsequent pregnancy.

Improved outcomes with delayed admission to post-acute care: results of a natural experiment.

PURPOSE: To determine the effectiveness of a post-acute care scheme by exploiting a natural experiment. METHODS: We used a reduction in funding for an Irish PAC scheme based in private nursing homes as a natural experiment to explore the effectiveness of this scheme in a single large general hospital. RESULTS: Compared with an equivalent 3-month period in 2017 (pre-change, N = 169), those admitted to PAC in 2019 (post-change, N = 179), spent a median 6 days longer in acute care, although total duration spent in healthcare settings was the same. Compared with 2017, readmissions to hospital within 90 days of discharge (43/179 (24.0% v 58/169 (34.3%), p = 0.03) and discharge to long-term care from the PAC facility (3 (1.7%) v 14 (8.3%), p = 0.004) were significantly lower in 2019. CONCLUSION: Our results suggest that the longer stay in acute care and shorter stay in PAC was beneficial for patients and led to improved outcomes.

Understanding factors associated with re-referral of youth for commercial sexual exploitation.

BACKGROUND: Since the passage of the Victims of Trafficking and Violence Prevention Act of 2000 in the United States, awareness has increased about the problem of commercial sexual exploitation of children (CSEC). Moreover, United States Federal law calls upon child welfare agencies to establish policies and practices that help identify and provide services to minors at risk of CSEC. Although awareness has increased about the problem of CSEC, little attention has been paid to understanding why some youths are re-referred to CSEC programs after initial referral and intervention. OBJECTIVE: The present study examines which factors drive re-referrals of youths for CSEC concerns. PARTICIPANTS AND SETTING: Data about a population of high-risk youths (n = 416) referred to a CSEC-specific program in the Northeast of the United States between 2011 and 2018. METHODS: Using logistic regression analyses, we investigate what factors are associated with youth having multiple referrals. RESULTS: Youths with multiple referrals were more likely to have histories of missing from care (OR = 2.996, p < 0.001), substance misuse (OR = 2.802, p < 0.01), and greater agency involvement (OR = 1.260, p < 0.05). However, youths with multiple referrals were not at heightened risk of CSEC as compared to youths that were not re-referred. CONCLUSION: The results demonstrate that re-referred youths meet the profile of a victim as depicted on screening and assessment instruments, which has important implications for victim services and referral systems dedicated to identifying CSEC and protecting youths who may experience re-victimization for CSEC.

Proteomic Profiling of IgG1 Producing CHO Cells Using LC/LC-SPS-MS3: The Effects of Bioprocessing Conditions on Productivity and Product Quality.

The biopharmaceutical market is dominated by monoclonal antibodies, the majority of which are produced in Chinese hamster ovary (CHO) cell lines. Intense cell engineering, in combination with optimization of various process parameters results in increasing product titers. To enable further improvements in manufacturing processes, detailed information about how certain parameters affect cellular mechanisms in the production cells, and thereby also the expressed drug substance, is required. Therefore, in this study the effects of commonly applied changes in bioprocessing parameters on an anti-IL8 IgG1 producing CHO DP-12 cell line were investigated on the level of host cell proteome expression combined with product quality assessment of the expressed IgG1 monoclonal antibody. Applying shifts in temperature, pH and dissolved oxygen concentration, respectively, resulted in altered productivity and product quality. Furthermore, analysis of the cells using two-dimensional liquid chromatography-mass spectrometry employing tandem mass tag based isotopic quantitation and synchronous precursor selection-MS3 detection revealed substantial changes in the protein expression profiles of CHO cells. Pathway analysis indicated that applied bioprocessing conditions resulted in differential activation of oxidative phosphorylation. Additionally, activation of ERK5 and TNFR1 signaling suggested an affected cell cycle. Moreover, in-depth product characterization by means of charge variant analysis, peptide mapping, as well as structural and functional analysis, revealed posttranslational and structural changes in the expressed drug substance. Taken together, the present study allows the conclusion that, in anti-IL8 IgG1 producing CHO DP-12 cells, an improved energy metabolism achieved by lowering the cell culture pH is favorable when aiming towards high antibody production rates while maintaining product quality.

Evaluation of a Multi-Session Group Designed to Prevent Commercial Sexual Exploitation of Minors: The "My Life My Choice" Curriculum.

The commercial sexual exploitation (CSE) of children is a consequential public health and criminal justice problem, but no CSE prevention programs have been evaluated. The Boston-based My Life My Choice (MLMC) program offers a multisession psychoeducation group to girls who are identified as "at-disproportionate-risk" for CSE victimization and trains other agencies throughout the U.S. to offer this curriculum. The curriculum was designed to improve knowledge about the commercial sex industry and shift-related attitudes and behaviors. The current project was a multi-year, multi-site evaluation to assess the effectiveness of the MLMC prevention group. Using a one-group longitudinal design, changes in participant behavior and CSE knowledge were measured at baseline (n = 354), upon group completion (n = 296), and 3 months after group completion (n = 241). The sample was 95% female-identified, 28% Black/African American, 26% White/non-Hispanic, 25% Hispanic/Latina, and 22% other race. The mean age of participants was 15.6 years old. Approximately 28% identified as bisexual, and 10% identified as lesbian, asexual, pansexual, or other. In multivariable-adjusted models, participants reported fewer episodes of sexually explicit behavior at follow up as compared to baseline (relative risk [RR]: 0.52, 95% confidence interval [CI]: 0.37-0.72 at Follow-up 1, and 0.53, 95% CI: 0.35-0.82 at Follow-up 2). Participants were 24% less likely to report dating abuse at Follow-up 2 as compared to baseline (p = .06). In addition, as compared to baseline, participants were 40% more likely to have given help or information about CSE to a friend at Follow-up 2, and participants demonstrated increased knowledge and awareness about CSE and its harms over the follow-up period. Although additional evaluation using a comparison group and long-term follow up would increase confidence that observed changes are attributable to the group instead of other factors, results suggest that the MLMC curriculum may be effective in reducing the risk of CSE and improving other conditions for youth who are at-disproportionate-risk of CSE.

Exposure to Multiple Forms of Bias Victimization on Youth and Young Adults: Relationships with Trauma Symptomatology and Social Support.

Research has documented that a significant portion of youth are exposed to bias victimization. However, less is known about whether experiencing certain types of bias victimization (e.g., sexual orientation bias) is more or less likely to be related to a more extensive bias victimization history (i.e., experiencing multiple types of bias victimization) and whether exposure to multiple types of bias victimization explains any relationships between specific types of bias victimization and negative outcomes. To address these gaps, the current study explores relationships between exposure to multiple types of bias-motivated victimization, trauma symptomatology and perceived social support. Participants were 854 youth and young adults (60.9% female) from three higher risk communities who completed a survey on personal experiences with bias-related victimization. The average age of participants was 16.6 years; 28.5% of the sample described themselves as Black or African American; 13.4% as Hispanic or Latino (any race); 45.3% as White, and 12.8% as another race. Sixty-nine percent of the sample described their sexual orientation as heterosexual; 8.9% as gay, lesbian, or homosexual; 12.5% as bisexual; and 9.5% as another sexual orientation. Sixty-three percent of participants reported at least one type of bias victimization in their lifetime, and more than one in three youth (38.7%) experienced two or more types of bias victimization in their lifetimes (18.1% two types, 12.1% three types, and 8.5% four or more types). Experiencing multiple types of bias victimization was related to higher trauma symptomatology and less perceived social support. Experiencing multiple types of bias victimization attenuated or eliminated the association between individual types of bias victimization and well-being. The findings contribute to a growing body of research demonstrating the damaging mental health effects of occupying multiple marginalized statuses, and points to the cumulation of bias victimization experiences as an important factor contributing to significant differences in well-being and support among youth and young adults.

Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies.

With the size of the biopharmaceutical market exponentially increasing, there is an aligned growth in the importance of data-rich analyses, not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships. In monoclonal antibodies, many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known. The importance of their function focuses analytical research efforts on the development of robust, accurate and fast methods to support drug development and quality control. Released N-glycan analysis is considered as the gold standard for glycosylation characterisation; however, it is not the only method for quantitative analysis of glycoform heterogeneity. In this study, ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies. While observing good comparability between the quantitative results generated, it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow according to application and the desired depth of data generated.

A longitudinal evaluation of a survivor-mentor program for child survivors of sex trafficking in the United States.

BACKGROUND: Commercial sexual exploitation (CSE) of children is a significant public health and criminal justice problem, but there are few evaluated models of CSE mentorship service. OBJECTIVES: To assess whether youth who participated in a CSE survivor-mentor program evidenced changes in CSE victimization, dating abuse victimization, health, delinquency, social support, and coping during the year following their enrollment in the program. PARTICIPANTS: 41 youth who were CSE-experienced at baseline (72%) or determined very high risk, 11-18 years old, 95% female, 58% heterosexual, 29% White, 29% Hispanic, and 42% other races/ethnicities. SETTING: An urban city in the Northeast United States. METHODS: We used a one-group repeated measures design and a GEE analysis. Data were collected at baseline, six months after baseline (71% follow-up) and 12 months after baseline (68% follow-up). RESULTS: At baseline 72% could be characterized as CSE-experienced, while at 6 months the percentage decreased to 24% (p < 0.001) and at 12 months to 14% (p < 0.001). After 6 months of receiving survivor-mentor services, youth were less likely to have experienced CSE, engaged in sexually explicit behavior (SEB), used illicit drugs, engaged in delinquent behavior, been arrested or detained by police, and they had better social support and coping skills. After 12 months, youth were less likely to have experienced CSE, to have engaged in delinquent behavior, be arrested or detained by police, and had improved coping skills. CONCLUSION: Findings demonstrate that youth who received survivor-mentor services from MLMC experienced improved well-being and less drug use, delinquent behavior, and exploitation.

Enhancing the Identification of Commercial Sexual Exploitation Among a Population of High-Risk Youths Using Predictive Regularization Models.

Despite an increasing awareness about the existence and harms of commercial sexual exploitation of children (CSEC), the identification of victims remains a challenge for practitioners, hindering their ability to provide appropriate services. Tools that gauge risk of CSEC support the identification of victims but are underdeveloped because most tools assess risk of CSEC within a general youth population. An understanding of what predicts actual CSEC victimizations among youths at higher risk of CSEC due to experiences of childhood adversities has been left unassessed. Research in this area is limited in part because traditional methods do not allow for an assessment of the unique impact of childhood adversities that tend to co-occur. To address these difficulties, the current study applied predictive regularization methods to identify the most decisive risk items for CSEC. Proximal risk of CSEC was assessed among 317 youths who were referred to a specialized program in the Northeast of the United States due to suspicion of CSEC. With an innovative methodological approach, this study seeks to prompt other scholars to examine risk utilizing novel techniques and provides a foundation for the development of concise tools that assess risk of CSEC among populations of youths at higher levels of risk.

Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies / 药物分析学报

With the size of the biopharmaceutical market exponentially increasing, there is an aligned growth in the importance of data-rich analyses, not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships. In monoclonal antibodies, many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known. The importance of their function focuses analytical research efforts on the development of robust, accurate and fast methods to support drug development and quality control. Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however, it is not the only method for quantitative analysis of glycoform heterogeneity. In this study, ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies. While observing good comparability between the quantitative results generated, it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow ac-cording to application and the desired depth of data generated.

Ethical and Practical Considerations for Collecting Research-Related Data from Commercially Sexually Exploited Children.

This article presents seven challenges of collecting primary (i.e., firsthand) data from commercially sexually exploited children (CSEC). We drew on our research team's experience collecting longitudinal data from 28 CSEC survivors with a 12-month follow-up period. We used both face-to-face and electronic group brainstorming methods to nominate a list of research-related challenges. The two main themes that were identified were challenges that can limit data quality and concerns about the impact of research on participants, researchers, and others. The three challenges related to data quality are (1) the age of the research participants; (2) questions about obtaining informed consent from parents or guardians; and (3) the over-interrogation of CSEC youth. The four challenges related to concerns about the impact of research were (4) concerns that research participation may further exploit youth; (5) staying in the role of researcher and refraining from providing advocacy; (6) secondary trauma and burnout experienced by research staff; and (7) the additional burden that research and data collection may place on the advocates and direct service providers. Because the process of collecting data from CSEC youth can be complicated, and rife with ethical and practical challenges, we have relayed our experiences with seven specific research-related challenges in order to stimulate discourse and further progress in the field.

Charge Variant Analysis of Monoclonal Antibodies Using Direct Coupled pH Gradient Cation Exchange Chromatography to High-Resolution Native Mass Spectrometry.

Charge variant analysis (CVA) of monoclonal antibodies (mAbs) using cation exchange chromatography is routinely used as a fingerprint of the distribution of posttranslational modifications present on the molecule. Traditional salt or pH based eluents are not suited for direct coupling to mass spectrometry due to nonvolatility or high ionic strength. This makes further analysis complicated when an alteration in the charge variant profile or the emergence of an additional peak is encountered. Here, the use of pH gradient elution using volatile, low ionic strength buffers is reported with direct coupling to high-resolution Orbitrap mass spectrometry. The development of a universal method based on pH elution was explored using a number of mAb drug products. Optimized methods facilitated the separation and identification of charge variants including individual glycoforms of the mAbs investigated using the same buffer system but with tailored gradient slopes. The developed method represents an exciting advance for the characterization of biopharmaceuticals as intact entities through the combination of native charge variant separations with high-resolution native mass spectrometry.

Proteomics in biomanufacturing control: Protein dynamics of CHO-K1 cells and conditioned media during apoptosis and necrosis.

Cell viability has a critical impact on product quantity and quality during the biomanufacturing of therapeutic proteins. An advanced understanding of changes in the cellular and conditioned media proteomes upon cell stress and death is therefore needed for improved bioprocess control. Here, a high pH/low pH reversed phase data independent 2D-LC-MSE discovery proteomics platform was applied to study the cellular and conditioned media proteomes of CHO-K1 apoptosis and necrosis models where cell death was induced by staurosporine exposure or aeration shear in a benchtop bioreactor, respectively. Functional classification of gene ontology terms related to molecular functions, biological processes, and cellular components revealed both cell death independent and specific features. In addition, label free quantitation using the Hi3 approach resulted in a comprehensive shortlist of 23 potential cell viability marker proteins with highest abundance and a significant increase in the conditioned media upon induction of cell death, including proteins related to cellular stress response, signal mediation, cytoskeletal organization, cell differentiation, cell interaction as well as metabolic and proteolytic enzymes which are interesting candidates for translating into targeted analysis platforms for monitoring bioprocessing response and increasing process control.

MYC regulates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma associated with poor outcome and chemoresistance.

Intratumoral phenotypic heterogeneity has been described in many tumor types, where it can contribute to drug resistance and disease recurrence. We analyzed ductal and neuroendocrine markers in pancreatic ductal adenocarcinoma, revealing heterogeneous expression of the neuroendocrine marker Synaptophysin within ductal lesions. Higher percentages of Cytokeratin-Synaptophysin dual positive tumor cells correlate with shortened disease-free survival. We observe similar lineage marker heterogeneity in mouse models of pancreatic ductal adenocarcinoma, where lineage tracing indicates that Cytokeratin-Synaptophysin dual positive cells arise from the exocrine compartment. Mechanistically, MYC binding is enriched at neuroendocrine genes in mouse tumor cells and loss of MYC reduces ductal-neuroendocrine lineage heterogeneity, while deregulated MYC expression in KRAS mutant mice increases this phenotype. Neuroendocrine marker expression is associated with chemoresistance and reducing MYC levels decreases gemcitabine-induced neuroendocrine marker expression and increases chemosensitivity. Altogether, we demonstrate that MYC facilitates ductal-neuroendocrine lineage plasticity in pancreatic ductal adenocarcinoma, contributing to poor survival and chemoresistance.

Glycosylation Analysis of Therapeutic Glycoproteins Produced in CHO Cells.

In the last decades, the number of approved therapeutic proteins drugs is increasing exponentially and a large number of new therapeutic entities are progressing through clinical trials, solidifying biologics as the most promising class of pharmaceuticals on the market. Several cell lines are available for biopharmaceutical processes but mammalian cells are preferred since they give fewer problems for immunogenicity as they produce human-like post-translational modifications (PTMs). Glycosylation is the most common and complex (for both bioprocess engineering and quality control) of these modifications. Obtaining the desired glycosylation pattern is crucial for therapeutic proteins as it can impact significantly stability, half-life and safety as well as driving molecular processes, modifying the way drug interacts with patients' cells. As a consequence, glycosylation (like other PTMs) needs to be regulated and accurately analyzed during biopharmaceutical production. Herein we describe and discuss the analytical approaches for glycosylation analysis of therapeutic glycoproteins produced in CHO (Chinese Hamster Ovary) cells. This chapter will describe glycoprotein purification after separation from producing cell lines, N-glycan release and their variants fine structural characterization through mass spectrometry techniques.

Race differences in depression vulnerability following Hurricane Katrina.

OBJECTIVE: This study investigated whether racial disparities in depression were present after Hurricane Katrina. METHOD: Data were gathered from 932 New Orleans residents who were present when Hurricane Katrina struck, and who returned to New Orleans the following year. Multiple logistic regression models evaluated racial differences in screening positive for depression (a score ≥16 on the Center for Epidemiologic Studies Depression Scale), and explored whether differential vulnerability (prehurricane physical and mental health functioning and education level), differential exposure to hurricane-related stressors, and loss of social support moderated and/or reduced the association of race with depression. RESULTS: A univariate logistic regression analysis showed the odds for screening positive for depression were 86% higher for African Americans than for Caucasians (odds ratio [OR] = 1.86 [1.28-2.71], p = .0012). However, after controlling simultaneously for sociodemographic characteristics, preexisting vulnerabilities, social support, and trauma-specific factors, race was no longer a significant correlate for screening positive for depression (OR = 1.54 [0.95-2.48], p = .0771). CONCLUSIONS: The racial disparity in postdisaster depression seems to be confounded by sociodemographic characteristics, preexisting vulnerabilities, social support, and trauma-specific factors. Nonetheless, even after adjusting for these factors, there was a nonsignificant trend effect for race, which could suggest race played an important role in depression outcomes following Hurricane Katrina. Future studies should examine these associations prospectively, using stronger assessments for depression, and incorporate measures for discrimination and segregation, to further understand possible racial disparities in depression after Hurricane Katrina. (PsycINFO Database Record