Demonstrating service delivery models for effective initiation and retention on pre-exposure prophylaxis (PrEP) among female bar workers in Dar es Salaam, Tanzania: A double randomized intervention study protocol.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in preventing HIV infection. Female Bar Workers (FBWs) often act as informal sex workers, placing them at risk of HIV infection. Despite expressing interest in PrEP, FBWs face barriers to accessing public-sector clinics where PrEP is delivered. We developed a study to compare the effectiveness of workplace-based PrEP provision to standard-of-care facility-based provision for PrEP initiation, retention and adherence among FBWs. METHODS: In this double-randomized intervention study, FBWs aged 15 years and above will be screened, consented and initiated on PrEP (emtricitabine/tenofovir disoproxil), and followed for six months. Participants will be randomized at the bar level and offered PrEP at their workplace or at a health facility. Those who are initiated will be independently individually randomized to either receive or not receive an omni-channel PrEP champion intervention (support from an experienced PrEP user) to improve PrEP adherence. We expect to screen 1,205 FBWs to enroll at least 160 HIV negative women in the study. Follow-up visits will be scheduled monthly. HIV testing will be performed at baseline, month 1, 4 and 6; and TDF testing at months 2 and 6. Primary outcomes for this trial are: (1) initiation on PrEP (proportion of those offered PrEP directly observed to initiate PrEP); and (2) adherence to PrEP (detectable urine TDF drug level at 6-months post-enrollment). The primary outcomes will be analyzed using Intention-to-Treat (ITT) analyses. DISCUSSION: Using a randomized trial design, we will evaluate two interventions aiming to reduce barriers to uptake and retention on PrEP among FBWs, a vulnerable population at risk of HIV acquisition and onward transmission. If these interventions prove effective in promoting PrEP among FBWs, they could assist in abating the HIV epidemic in Africa. TRIAL REGISTRATION: Registered with German Clinical Trials Register (www.drks.de) on 29 April 2020; Registration number DRKS00018101.

Multisensory processing impacts memory for objects and their sources.

Multisensory object processing improves recognition memory for individual objects, but its impact on memory for neighboring visual objects and scene context remains largely unknown. It is therefore unclear how multisensory processing impacts episodic memory for information outside of the object itself. We conducted three experiments to test the prediction that the presence of audiovisual objects at encoding would improve memory for nearby visual objects, and improve memory for the environmental context in which they occurred. In Experiments 1a and 1b, participants viewed audiovisual-visual object pairs or visual-visual object pairs with a control sound during encoding and were subsequently tested on their memory for each object individually. In Experiment 2, objects were paired with semantically congruent or meaningless control sounds and appeared within four different scene environments. Memory for the environment was tested. Results from Experiments 1a and 1b showed that encoding a congruent audiovisual object did not significantly benefit memory for neighboring visual objects, but Experiment 2 showed that encoding a congruent audiovisual object did improve memory for the environments in which those objects were encoded. These findings suggest that multisensory processing can influence memory beyond the objects themselves and that it has a unique role in episodic memory formation. This is particularly important for understanding how memories and associations are formed in real-world situations, in which objects and their surroundings are often multimodal.

Object-based attention during scene perception elicits boundary contraction in memory.

Boundary contraction and extension are two types of scene transformations that occur in memory. In extension, viewers extrapolate information beyond the edges of the image, whereas in contraction, viewers forget information near the edges. Recent work suggests that image composition influences the direction and magnitude of boundary transformation. We hypothesize that selective attention at encoding is an important driver of boundary transformation effects, selective attention to specific objects at encoding leading to boundary contraction. In this study, one group of participants (N = 36) memorized 15 scenes while searching for targets, while a separate group (N = 36) just memorized the scenes. Both groups then drew the scenes from memory with as much object and spatial detail as they could remember. We asked online workers to provide ratings of boundary transformations in the drawings, as well as how many objects they contained and the precision of remembered object size and location. We found that search condition drawings showed significantly greater boundary contraction than drawings of the same scenes in the memorize condition. Search drawings were significantly more likely to contain target objects, and the likelihood to recall other objects in the scene decreased as a function of their distance from the target. These findings suggest that selective attention to a specific object due to a search task at encoding will lead to significant boundary contraction.

Evaluation of patient health outcomes of a student-run free clinic in East Harlem.

BACKGROUND: Most United States medical schools have affiliated student-run free clinics, but the quality of services provided in such contexts compared to national metrics is unknown. This study determines whether a student-run, attending-supervised free clinic servicing a low-income and minority race patient population in New York City can meet national metrics of care. METHODS: Through chart review from January 1, 2020 to December 31, 2020, patient outcomes and service utilization in the Healthcare Effectiveness Data and Information Set were examined and compared to national rates of patients using Medicaid HMO or Medicare. Patients are ≥ 21 years of age, residents of East Harlem, and ineligible for health insurance because of legal residency requirements. The majority identify as Hispanic and speak Spanish as their primary language. All patients who were seen in the clinic during the 2020 calendar year were included. The primary study outcome is the number of Healthcare Effectiveness Data and Information Set measures in which patients, seen in a student-run free clinic, meet or exceed national comparisons. RESULTS: The healthcare outcomes of 238 patients, mean age 47.8 years and 54.6% female, were examined in 18 Healthcare Effectiveness Data and Information Set measures. The student-run free clinic met or exceeded national metrics in 16 out of 18 categories. CONCLUSIONS: The student-run free clinic met or exceeded the national standard of care according to national metrics. Evidence-based priorities have been clarified for future improvement. Other student-run free clinics should similarly evaluate the quality of their services.

Recurrent evolutionary switches of mitochondrial cytochrome c maturation systems in Archaeplastida.

Mitochondrial cytochrome c maturation (CCM) requires heme attachment via distinct pathways termed systems I and III. The mosaic distribution of these systems in Archaeplastida raises questions about the genetic mechanisms and evolutionary forces promoting repeated evolution. Here, we show a recurrent shift from ancestral system I to the eukaryotic-specific holocytochrome c synthase (HCCS) of system III in 11 archaeplastid lineages. Archaeplastid HCCS is sufficient to rescue mutants of yeast system III and Arabidopsis system I. Algal HCCS mutants exhibit impaired growth and respiration, and altered biochemical and metabolic profiles, likely resulting from deficient CCM and reduced cytochrome c-dependent respiratory activity. Our findings demonstrate that archaeplastid HCCS homologs function as system III components in the absence of system I. These results elucidate the evolutionary trajectory and functional divergence of CCM pathways in Archaeplastida, providing insight into the causes, mechanisms, and consequences of repeated cooption of an entire biological pathway.

Terms of debate: Consensus definitions to guide the scientific discourse on visual distraction.

Hypothesis-driven research rests on clearly articulated scientific theories. The building blocks for communicating these theories are scientific terms. Obviously, communication - and thus, scientific progress - is hampered if the meaning of these terms varies idiosyncratically across (sub)fields and even across individual researchers within the same subfield. We have formed an international group of experts representing various theoretical stances with the goal to homogenize the use of the terms that are most relevant to fundamental research on visual distraction in visual search. Our discussions revealed striking heterogeneity and we had to invest much time and effort to increase our mutual understanding of each other's use of central terms, which turned out to be strongly related to our respective theoretical positions. We present the outcomes of these discussions in a glossary and provide some context in several essays. Specifically, we explicate how central terms are used in the distraction literature and consensually sharpen their definitions in order to enable communication across theoretical standpoints. Where applicable, we also explain how the respective constructs can be measured. We believe that this novel type of adversarial collaboration can serve as a model for other fields of psychological research that strive to build a solid groundwork for theorizing and communicating by establishing a common language. For the field of visual distraction, the present paper should facilitate communication across theoretical standpoints and may serve as an introduction and reference text for newcomers.

Task-adaptive changes to the target template in response to distractor context: Separability versus similarity.

Theories of attention hypothesize the existence of an attentional template that contains target features in working or long-term memory. It is frequently assumed that the template contains a veridical copy of the target, but recent studies suggest that this is not true when the distractors are linearly separable from the target. In such cases, target representations shift "off-veridical" in response to the distractor context, presumably because doing so is adaptive and increases the representational distinctiveness of targets from distractors. However, some have argued that the shifts may be entirely explained by perceptual biases created by simultaneous color contrast. Here we address this debate and test the more general hypothesis that the target template is adaptively shaped by elements of the distractor context needed to distinguish targets from distractors. We used a two-dimensional target and separately manipulated the linear separability of one dimension (color) and the visual similarity of the other (orientation). We found that target shifting along the linearly separable color dimension was dependent on the similarity of targets-to-distractors along the other dimension. The target representations were consistent with a postexperiment strategy questionnaire in which participants reported using color more when orientation was hard to use, and orientation more when it was easier to use. We conclude that the target template is task-adaptive and exploit features in the distractor context that most predictably distinguish targets from distractors to increase visual search efficiency. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Learned associations serve as target proxies during difficult but not easy visual search.

The target template contains information in memory that is used to guide attention during visual search and is typically thought of as containing features of the actual target object. However, when targets are hard to find, it is advantageous to use other information in the visual environment that is predictive of the target's location to help guide attention. The purpose of these studies was to test if newly learned associations between face and scene category images lead observers to use scene information as a proxy for the face target. Our results showed that scene information was used as a proxy for the target to guide attention but only when the target face was difficult to discriminate from the distractor face; when the faces were easy to distinguish, attention was no longer guided by the scene unless the scene was presented earlier. The results suggest that attention is flexibly guided by both target features as well as features of objects that are predictive of the target location. The degree to which each contributes to guiding attention depends on the efficiency with which that information can be used to decode the location of the target in the current moment. The results contribute to the view that attentional guidance is highly flexible in its use of information to rapidly locate the target.

Mental health, stigma and the quality of life of people affected by neglected tropical diseases of the skin in Kasai Province, Democratic Republic of the Congo: a sex-disaggregated analysis.

BACKGROUND: Worldwide, persons affected by skin Neglected Tropical Diseases (NTDs) may experience stigma and discrimination, which could lead to impaired societal functioning and poor mental wellbeing. Evidence of comorbidity of NTDs and mental health conditions is dominated by Leprosy, largely lacking in post-conflict areas, and rarely disaggregated by sex. METHODS: This cross-sectional survey is the first to explore depression, anxiety, stigma, and quality of life amongst people affected by Lymphatic Filariasis, Buruli Ulcer, Onchocerciasis or Leprosy in the Democratic Republic of the Congo. After a census through active case identification, the survey was completed by 118 persons (response rate 94.4%). RESULTS: In total, 58.3% of men and 80.0% of women screened positive for major depressive disorder (PHQ-9). Symptoms indicative of generalised anxiety disorder (GAD-7) were displayed by 54.8% of men and 62.2% of women. Being female, having a disability, experiencing stigma and lower physical quality of life were predictors of depression. Anxiety was predicted by age, physical quality of life, disability (for men only) and environmental quality of life (for women only). CONCLUSIONS: Integrated, intersectoral and gender-sensitive initiatives are needed to respond to the many biopsychosocial challenges that persons affected face. CONTEXTE: Dans le monde entier, les personnes atteintes de maladies tropicales négligées (MTN) peuvent faire l'objet d'une stigmatisation et d'une discrimination, ce qui peut entraîner une altération du fonctionnement de la société et un mauvais bien-être mental. Les preuves de la comorbidité des MTN et des troubles de la santé mentale sont dominées par la lèpre, manquent largement dans les zones post-conflit et sont rarement ventilées par sexe. MÉTHODES UTILISÉES: Cette enquête transversale est la première à explorer la dépression, l'anxiété, la stigmatisation et la qualité de vie chez les personnes atteintes de filariose lymphatique, d'ulcère de Buruli, d'onchocercose ou de lèpre en République démocratique du Congo. Après un recensement par identification active des cas, 118 personnes ont répondu à l'enquête (taux de réponse 94,4%). RÉSULTATS: Au total, 58,3% des hommes et 80,0% des femmes ont été dépistés positifs pour un trouble dépressif majeur (PHQ-9). Des symptômes indiquant un trouble anxieux généralisé (GAD-7) ont été observés chez 54,8 % des hommes et 62,2 % des femmes. Le fait d'être une femme, d'avoir un handicap, d'être stigmatisé et d'avoir une qualité de vie physique inférieure était un facteur prédictif de la dépression. L'anxiété était prédite par l'âge, la qualité de vie physique, le handicap (pour les hommes uniquement) et la qualité de vie environnementale (pour les femmes uniquement). CONCLUSIONS: Des initiatives intégrées, intersectorielles et sensibles au genre sont nécessaires pour répondre aux nombreux défis biopsychosociaux auxquels sont confrontées les personnes touchées. ANTECEDENTES: En todo el mundo, las personas afectadas por Enfermedades Tropicales Desatendidas (ETD) cutáneas pueden sufrir estigmatización y discriminación, lo que podría conducir a un deterioro del funcionamiento social y a un bienestar mental deficiente. La evidencia científica sobre la comorbilidad de las ETD y las afecciones mentales está dominada por la lepra, en general insuficiente en zonas post-conflicto y rara vez se desglosan por sexo. MÉTODOS: Esta encuesta transversal es la primera que explora la depresión, la ansiedad, el estigma y la calidad de vida entre las personas afectadas por la filariasis linfática, la úlcera de Buruli, la oncocercosis o la lepra en la República Democrática del Congo. Tras un censo mediante identificación activa de casos, la encuesta fue completada por 118 personas (tasa de respuesta del 94,4%). RESULTADOS: En total, el 58,3% de los hombres y el 80,0% de las mujeres arrojaron resultados positivos para el trastorno depresivo mayor (PHQ-9). El 54,8% de los hombres y el 62,2% de las mujeres presentaban síntomas indicativos de trastorno de ansiedad generalizada (TAG-7). Ser mujer, tener una discapacidad, sufrir estigmatización y una menor calidad de vida física fueron factores predictivos de la depresión. La edad, la calidad de vida física, la discapacidad (sólo en el caso de los hombres) y la calidad de vida ambiental (sólo en el caso de las mujeres) fueron factores predictivos de la ansiedad. CONCLUSIONES: Se necesitan iniciativas integradas, intersectoriales y con perspectiva de género para responder a los numerosos retos biopsicosociales a los que se enfrentan las personas afectadas.

Support, networks, and relationships: Findings from a mixed-methods evaluation of a mentorship programme for early career women researchers in sexual and reproductive health and rights.

Low research output among women researchers in health research has been linked to inadequate mentorship opportunities for early career women researchers and particularly in sexual and reproductive health and rights (SRHR) field. Mentorship has been recognized as a contributor to strengthening research capacity and as beneficial for both mentors and mentees. Women researchers oftentimes experience negative impacts of organizational and structural gender inequities related to formal and informal mentoring. In 2020, the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction at WHO launched a mentorship programme for early career SRHR women researchers from low- and middle-income countries. The programme sought to provide professional skill-building, promote and share networking opportunities, and offer support in navigating personal and professional life. We conducted a convergent parallel mixed-methods evaluation of the 2020 pilot programme, which included 26 participants, through an online survey and semi-structured in-depth interviews (IDIs). Data collection occurred between March and May 2022. Nineteen responded to the online survey (12 mentees, 7 mentors) and 11 IDIs (7 mentees, 4 mentors) were completed. Based on a preliminary framework, we used deductive and inductive methods to identify six themes: views on mentorship; reasons for applying and expectations of participation in the programme; preferred aspects of programme implementation; challenges with the programme implementation; perceived lasting benefits of the programme; and recommendations for improvement. All participants found the initial training useful, most discussed work-life prioritization throughout the mentorship relationship, and most planned to continue with the relationship. There appear to be ample benefits to mentorship, especially when planned and implemented in a structured manner. These attributes can be particularly beneficial when they are conceived as a two-way relationship of mutual learning and support, and especially for women at the start of their research careers as they navigate structural gender inequities.

Prefrontal Cortex Codes Representations of Target Identity and Feature Uncertainty.

Many objects in the real world have features that vary over time, creating uncertainty in how they will look in the future. This uncertainty makes statistical knowledge about the likelihood of features critical to attention demanding processes such as visual search. However, little is known about how the uncertainty of visual features is integrated into predictions about search targets in the brain. In the current study, we test the idea that regions prefrontal cortex code statistical knowledge about search targets before the onset of search. Across 20 human participants (13 female; 7 male), we observe target identity in the multivariate pattern and uncertainty in the overall activation of dorsolateral prefrontal cortex (DLPFC) and inferior frontal junction (IFJ) in advance of the search display. This indicates that the target identity (mean) and uncertainty (variance) of the target distribution are coded independently within the same regions. Furthermore, once the search display appears the univariate IFJ signal scaled with the distance of the actual target from the expected mean, but more so when expected variability was low. These results inform neural theories of attention by showing how the prefrontal cortex represents both the identity and expected variability of features in service of top-down attentional control.SIGNIFICANCE STATEMENT Theories of attention and working memory posit that when we engage in complex cognitive tasks our performance is determined by how precisely we remember task-relevant information. However, in the real world the properties of objects change over time, creating uncertainty about many aspects of the task. There is currently a gap in our understanding of how neural systems represent this uncertainty and combine it with target identity information in anticipation of attention demanding cognitive tasks. In this study, we show that the prefrontal cortex represents identity and uncertainty as unique codes before task onset. These results advance theories of attention by showing that the prefrontal cortex codes both target identity and uncertainty to implement top-down attentional control.

Functional, cognitive, and cerebrovascular aspects of depression before coronary artery bypass graft surgery: Testing the vascular depression hypothesis.

OBJECTIVE: Depression in patients undergoing coronary artery graft bypass (CABG) surgery is associated with morbidity and mortality, making its early identification and clinical management crucial. Vasculopathy and older age, hallmarks of patients requiring CABG, are also features of vascular depression. In this study, we assess for features of vascular depression in patients undergoing CABG surgery. METHODS: This is a cross-sectional analysis of a single-site prospective observational cohort study of patients undergoing CABG surgery. Subjects were assessed preoperatively using the Depression Interview and Structured Hamilton (DISH), depression scales, transcranial Doppler, neuropsychological testing, and clinical dementia rating (CDR). RESULTS: Of 161 subjects (mean age 66.2 ± 9.3, female 25%) who completed DISH, 18 had major or minor depression, 17 of whom had a past history of major or minor depression (mean age of onset 35.8 years-old). Pre-CABG depression was associated with greater functional impairment on CDR Sum of Boxes (OR = 3.7, 95% CI: 1.4, 9.7) and worse performance on letter fluency test (OR = 0.90, 95% CI: 0.81, 0.99) and trail-making tests (A: OR = 1.06, 95% CI: 1.01, 1.12; B: OR 1.02, 95% CI: 1.01, 1.04). Pre-CABG depression was not associated with middle cerebral artery (MCA) stenosis. CONCLUSIONS: Pre-CABG depression is associated with cognitive and functional impairment similar to vascular depression, but we did not find evidence of an association with older age of onset and MCA stenosis. Further studies on white matter disease in this population are needed to examine the vascular depression hypothesis for pre-CABG depression.

Stakeholder perspectives on interventions to improve HIV pre-exposure prophylaxis uptake and continuation in Lesotho: A participant-ranked preferences study.

Low uptake and high discontinuation remain major obstacles to realizing the potential of Pre-Exposure Prophylaxis (PrEP) in changing the trajectory of the HIV epidemic. We conducted a card sorting and ranking exercise with 155 local stakeholders to determine their views on the most important barriers and most promising interventions to achieving high PrEP coverage. Stakeholders were a purposive sample of PrEP policymakers and implementing partners (n = 7), healthcare providers (n = 51), and end-users (n = 97). End-users included adults who were currently using PrEP (n = 55), formerly using PrEP (n = 36), and those who were offered PrEP but declined (n = 6). Participants sorted pre-selected interventions and barriers to PrEP coverage into three piles-most, somewhat, and least important. Participants then ranked interventions and barriers in the "most important" piles in ascending order of significance. Ranked preferences were analyzed as voting data to identify the smallest set of candidates for which each candidate in the set would win in a two-candidate election against any candidate outside the set. Participants viewed a lack of PrEP awareness as the most important barrier to PrEP uptake for women, and a fear of HIV testing for men. Community-based HIV testing was ranked as the most promising intervention to improve PrEP uptake for both men and women. Perceived or experienced stigma was seen as an important barrier for PrEP continuation for both men and women, with an additional important barrier for men being daily activities that compete with the time needed to take a daily pill. Adherence counseling and multi-month PrEP prescriptions were seen as the most promising interventions to improve PrEP continuation. Our findings suggest community-based activities that generate PrEP demand (community-based HIV testing and mass media campaigns), reinforced with facility-based follow-up (counseling and multi-month prescription) could be promising interventions for PrEP programs that are aimed at the general adult population.

Winning the Lottery With Neural Connectivity Constraints: Faster Learning Across Cognitive Tasks With Spatially Constrained Sparse RNNs.

Recurrent neural networks (RNNs) are often used to model circuits in the brain and can solve a variety of difficult computational problems requiring memory, error correction, or selection (Hopfield, 1982; Maass et al., 2002; Maass, 2011). However, fully connected RNNs contrast structurally with their biological counterparts, which are extremely sparse (about 0.1%). Motivated by the neocortex, where neural connectivity is constrained by physical distance along cortical sheets and other synaptic wiring costs, we introduce locality masked RNNs (LM-RNNs) that use task-agnostic predetermined graphs with sparsity as low as 4%. We study LM-RNNs in a multitask learning setting relevant to cognitive systems neuroscience with a commonly used set of tasks, 20-Cog-tasks (Yang et al., 2019). We show through reductio ad absurdum that 20-Cog-tasks can be solved by a small pool of separated autapses that we can mechanistically analyze and understand. Thus, these tasks fall short of the goal of inducing complex recurrent dynamics and modular structure in RNNs. We next contribute a new cognitive multitask battery, Mod-Cog, consisting of up to 132 tasks that expands by about seven-fold the number of tasks and task complexity of 20-Cog-tasks. Importantly, while autapses can solve the simple 20-Cog-tasks, the expanded task set requires richer neural architectures and continuous attractor dynamics. On these tasks, we show that LM-RNNs with an optimal sparsity result in faster training and better data efficiency than fully connected networks.

Motivations for pre-exposure prophylaxis uptake and decline in an HIV-hyperendemic setting: findings from a qualitative implementation study in Lesotho.

BACKGROUND: Pre-Exposure Prophylaxis (PrEP) has demonstrated clinical efficacy in preventing HIV infection, yet its uptake remains low. This study, conducted in five PrEP implementing districts in Lesotho, examined factors motivating persons at risk of HIV infection to adopt or reject PrEP when offered freely. METHODS: In-depth interviews were undertaken with stakeholders directly engaged with PrEP policy (n = 5), program implementation (n = 4), and use (current PrEP users = 55, former PrEP users = 36, and PrEP decliners (n = 6)). Focus group discussions (n = 11, 105 total participants) were conducted with health staff directly providing HIV and PrEP services. RESULTS: Demand for PrEP was reported highest among those at greatest risk for HIV acquisition: those in serodiscordant relationships and/or engaged in sex work. Culturally sensitive PrEP counseling was described as an opportunity to transfer knowledge, build trust, and address user concerns. Conversely, top-down counseling resulted in PrEP distrust and confusion about HIV status. Key motivations for PrEP uptake revolved around sustaining core social relationships, desire for safer conception, and caring for ailing relatives. The decline of PrEP initiation was driven by a combination of individual-level factors (risk perception, perceived side effects, disbelief of the drug's efficacy and PrEP's daily pill regimen), societal factors (lack of social support and HIV-related stigma), and structural factors related to PrEP access. CONCLUSIONS: Our findings suggest strategies for effective national PrEP rollout and implementation include: (1) demand creation campaigns which highlight positive aspects of PrEP, while simultaneously addressing apprehensions for uptake; (2) strengthening health provider counseling capacity; and (3) addressing societal and structural HIV-related stigma.

KaryoCreate: A CRISPR-based technology to study chromosome-specific aneuploidy by targeting human centromeres.

Aneuploidy, the presence of chromosome gains or losses, is a hallmark of cancer. Here, we describe KaryoCreate (karyotype CRISPR-engineered aneuploidy technology), a system that enables the generation of chromosome-specific aneuploidies by co-expression of an sgRNA targeting chromosome-specific CENPA-binding ɑ-satellite repeats together with dCas9 fused to mutant KNL1. We design unique and highly specific sgRNAs for 19 of the 24 chromosomes. Expression of these constructs leads to missegregation and induction of gains or losses of the targeted chromosome in cellular progeny, with an average efficiency of 8% for gains and 12% for losses (up to 20%) validated across 10 chromosomes. Using KaryoCreate in colon epithelial cells, we show that chromosome 18q loss, frequent in gastrointestinal cancers, promotes resistance to TGF-ß, likely due to synergistic hemizygous deletion of multiple genes. Altogether, we describe an innovative technology to create and study chromosome missegregation and aneuploidy in the context of cancer and beyond.

A synthesis of mercury research in the Southern Hemisphere, part 1: Natural processes.

Recent studies demonstrate a short 3-6-month atmospheric lifetime for mercury (Hg). This implies Hg emissions are predominantly deposited within the same hemisphere in which they are emitted, thus placing increasing importance on considering Hg sources, sinks and impacts from a hemispheric perspective. In the absence of comprehensive Hg data from the Southern Hemisphere (SH), estimates and inventories for the SH have been drawn from data collected in the NH, with the assumption that the NH data are broadly applicable. In this paper, we centre the uniqueness of the SH in the context of natural biogeochemical Hg cycling, with focus on the midlatitudes and tropics. Due to its uniqueness, Antarctica warrants an exclusive review of its contribution to the biogeochemical cycling of Hg and is therefore excluded from this review. We identify and describe five key natural differences between the hemispheres that affect the biogeochemical cycling of Hg: biome heterogeneity, vegetation type, ocean area, methylation hotspot zones and occurence of volcanic activities. We review the current state of knowledge of SH Hg cycling within the context of each difference, as well as the key gaps that impede our understanding of natural Hg cycling in the SH. The differences demonstrate the limitations in using NH data to infer Hg processes and emissions in the SH.

A synthesis of mercury research in the Southern Hemisphere, part 2: Anthropogenic perturbations.

Environmental mercury (Hg) contamination is a global concern requiring action at national scales. Scientific understanding and regulatory policies are underpinned by global extrapolation of Northern Hemisphere Hg data, despite historical, political, and socioeconomic differences between the hemispheres that impact Hg sources and sinks. In this paper, we explore the primary anthropogenic perturbations to Hg emission and mobilization processes that differ between hemispheres and synthesize current understanding of the implications for Hg cycling. In the Southern Hemisphere (SH), lower historical production of Hg and other metals implies lower present-day legacy emissions, but the extent of the difference remains uncertain. More use of fire and higher deforestation rates drive re-mobilization of terrestrial Hg, while also removing vegetation that would otherwise provide a sink for atmospheric Hg. Prevalent Hg use in artisanal and small-scale gold mining is a dominant source of Hg inputs to the environment in tropical regions. Meanwhile, coal-fired power stations continue to be a significant Hg emission source and industrial production of non-ferrous metals is a large and growing contributor. Major uncertainties remain, hindering scientific understanding and effective policy formulation, and we argue for an urgent need to prioritize research activities in under-sampled regions of the SH.