Stability and Structure of Potentially Atmospherically Relevant Glycine Ammonium Bisulfate Clusters.

New particle formation (NPF) is the process by which trace atmospheric acids and bases cluster and grow into particles that ultimately impact climate. Sulfuric acid concentration drives NPF, but nitrogen-containing bases promote the formation of more stable clusters via salt bridge formation. Recent computational efforts have suggested that amino acids can enhance NPF, predicting that they can stabilize new particles via multiple protonation sites, but there has yet to be experimental validation of these predictions. We used mass spectrometry and infrared spectroscopy to study the structure and stability of cationic clusters composed of glycine, sulfuric acid, and ammonia. When collisionally activated, clusters were significantly more likely to eliminate ammonia or sulfuric acid than glycine, while quantum chemical calculations predicted lower binding free energies for ammonia but similar binding free energies for glycine and sulfuric acid. These calculations predicted several low-energy structures, so we compared experimental and computed vibrational spectra to attempt to validate the computationally predicted minimum energy structure. Unambiguous identification of the experimental structure by comparison to these calculations was made difficult by the complexity of the experimental spectra and the fact that the identity of the computed lowest-energy structure depended strongly on temperature. If their vapors are present, amino acids are likely to be enriched in new particles by displacing more weakly bound ammonia, similar to the behavior of other atmospheric amines. The carboxylic acid groups were found to preferentially interact with other carboxylic acids, suggesting incipient organic/inorganic phase separation even at these small sizes.

Morphea patients with mucocutaneous involvement: A cross-sectional study from the Morphea in Adults and Children (MAC) cohort.

BACKGROUND: Demographic and clinical findings of patients with mucocutaneous morphea have not been well characterized, to our knowledge. OBJECTIVE: To determine the demographic and clinical characteristics of morphea patients with mucocutaneous lesions who were enrolled in the Morphea in Adults and Children cohort. METHODS: Cross-sectional study of 735 patients in the Morphea in Adults and Children cohort from 2007 to 2018. RESULTS: A total of 4.6% of linear morphea patients had oral involvement versus 2.4% among the entire cohort, whereas 10.3% of generalized morphea patients had genital involvement versus 3.7% among the entire cohort. Patients with genital lesions were older at disease onset than those with oral morphea (57 versus 11.5 years; P < .001) and had more frequent extragenital lichen sclerosus et atrophicus (59.2% versus 5.6%; P = .004). LIMITATIONS: Selection bias and limited number of affected subjects. CONCLUSION: Oral morphea lesions predominate in younger patients with facial linear morphea, whereas genital lesions predominate in postmenopausal women with overlying extragenital lichen sclerosus et atrophicus.

A CGE Framework for Modeling the Economics of Flooding and Recovery in a Major Urban Area.

Coastal cities around the world have experienced large costs from major flooding events in recent years. Climate change is predicted to bring an increased likelihood of flooding due to sea level rise and more frequent severe storms. In order to plan future development and adaptation, cities must know the magnitude of losses associated with these events, and how they can be reduced. Often losses are calculated from insurance claims or surveying flood victims. However, this largely neglects the loss due to the disruption of economic activity. We use a forward-looking dynamic computable general equilibrium model to study how a local economy responds to a flood, focusing on the subsequent recovery/reconstruction. Initial damage is modeled as a shock to the capital stock and recovery requires rebuilding that stock. We apply the model to Vancouver, British Columbia by considering a flood scenario causing total capital damage of $14.6 billion spread across five municipalities. GDP loss relative to a no-flood scenario is relatively long-lasting. It is 2.0% ($2.2 billion) in the first year after the flood, 1.7% ($1.9 billion) in the second year, and 1.2% ($1.4 billion) in the fifth year.

Measuring Patients' Experience of Rehabilitation Services Across the Care Continuum. Part II: Key Dimensions.

OBJECTIVES: To identify key dimensions of patients' experience across the rehabilitative care system and to recommend a framework to develop survey items that measure the rehabilitative care experience. DATA SOURCES: Data were sourced from a literature review that searched MEDLINE (PubMed), CINAHL (Ebsco), and PsycINFO (APA PsycNET) databases from 2004 to 2014, the reference lists of the final accepted articles, and hand searches of relevant journals. STUDY SELECTION: Four reviewers performed the screening process on 2472 articles; 33 were included for analysis. Interrater reliability was confirmed through 2 rounds of title review and 1 round of abstract review, with an average κ score of .69. DATA EXTRACTION: The final sample of 33 accepted articles was imported into a qualitative data analysis software application. Multiple levels of coding and a constant comparative methodology generated 6 themes. There were 502 discreet survey questions measuring patient experience that were categorized using the following dimensions: rehabilitative care ecosystem, client and informal caregiver engagement, patient and health care provider relation, pain and functional status, group and individual identity, and open ended. DATA SYNTHESIS: The most common survey questions examine the care delivery ecosystem (37%), the engagement of clients and their informal caregivers (24.9%), and the quality of relations between providers and patients (21.7%). Examination of patient's functional status and management of pain yielded (15.3%) of the instruments' questions. CONCLUSIONS: Currently available instruments and questions that measure patients' experience in rehabilitative care are unable to assess the performance of rehabilitative delivery systems that aspire to integrate care across the continuum. However, question panels derived from our 6 key themes may measure the key concepts that define rehabilitative care and facilitate measurement of patient experience at the system level.

Measuring Patients' Experience of Rehabilitation Services Across the Care Continuum. Part I: A Systematic Review of the Literature.

OBJECTIVE: To identify empirically tested survey instruments designed to measure patient experience across a rehabilitative care system. DATA SOURCES: A comprehensive search was conducted of the MEDLINE (PubMed), CINAHL (EBSCO), and PsycINFO (APA PsycNET) databases from 2004 to 2014. Further searches were conducted in relevant journals and the reference lists of the final accepted articles. STUDY SELECTION: Of 2472 articles identified, 33 were selected for inclusion and analysis. Articles were excluded if they were unrelated to rehabilitative care, were anecdotal or descriptive reports, or had a veterinary, mental health, palliative care, dental, or pediatric focus. Four reviewers performed the screening process. Interrater reliability was confirmed through 2 rounds of title review (30 articles each) and 1 round of abstract review (10 articles), with an average κ score of .69. DATA EXTRACTION: Data were extracted related to the instrument, study setting, and patient characteristics, including treated disease, type of rehabilitation (eg, occupational or physical therapy), methodology, sample size, and level of evidence. DATA SYNTHESIS: There were 25 discrete measurement instruments identified in the 33 articles evaluated. Seven of the instruments originated outside of the rehabilitative care sector, and only 1 measured service experience across the care continuum. CONCLUSIONS: As providers move to integrate rehabilitative care across the continuum from hospital to home, patients experience a system of care. Research is required to develop psychometrically tested instruments that measure patients' experience across a rehabilitative system.

Cost-effectiveness of a package of interventions for expedited antiretroviral therapy initiation during pregnancy in Cape Town, South Africa.

Initiating antiretroviral therapy (ART) early in pregnancy is an important component of effective interventions to prevent the mother-to-child transmission of HIV (PMTCT). The rapid initiation of ART in pregnancy(RAP) program was a package of interventions to expedite ART initiation in pregnant women in Cape Town, South Africa. Retrospective cost-effectiveness, sensitivity and threshold analyses were conducted of the RAP program to determine the cost-utility thresholds for rapid initiation of ART in pregnancy. Costs were drawn from a detailed micro-costing of the program. The overall programmatic cost was US$880 per woman and the base case cost-effectiveness ratio was US$1,160 per quality-adjusted lifeyear (QALY) saved. In threshold analyses, the RAP program remained cost-effective if mother-to-child transmission was reduced by C0.33 %; if C1.76 QALY were saved with each averted perinatal infection; or if RAP-related costs were under US$4,020 per woman. The package of rapid initiation services was very cost-effective, as compared to standard services in this setting. Threshold analyses demonstrated that the intervention required minimal reductions in perinatal infections in order to be cost-effective. Interventions for the rapid initiation of ART in pregnancy hold considerable potential as a cost-effective use of limited resources for PMTCT in sub-Saharan Africa.

Acceptability and challenges of rapid ART initiation among pregnant women in a pilot programme, Cape Town, South Africa.

Maternal antiretroviral therapy (ART) is a critical intervention in the prevention-of-mother-to child transmission (PMTCT) of HIV. In South Africa, many HIV-infected pregnant women commence ART late in pregnancy, and as a result, the duration of ART prior to delivery is often insufficient to prevent vertical transmission. To address this, we designed an intervention for the rapid initiation of ART in pregnancy (RAP), where patient's ART preparation occurred during rather than before treatment commencement. Here we report on the acceptability and the challenges of the RAP programme. We conducted 7 key informant and 27 semi-structured interviews with RAP participants. Participants were purposefully selected based on ART-eligibility and stage in the pregnancy to post-partum continuum. Interviews were conducted in participants' home language by trained fieldworkers, with key informant interviews conducted by the study investigators. The data were analysed using a framework analysis approach. Rapid initiation in pregnancy was acceptable to the majority of programme participants and protection of the woman's unborn child was the primary motivation for starting treatment. The key barrier was the limited time to accept the dual challenges of being diagnosed HIV-positive and eligible for life-long ART. Truncated time also limited the opportunity for disclosure to others. Despite these and other barriers, most women found the benefits of rapid ART commencement outweighed the challenges, with 91% of women initiated onto ART starting the same day treatment eligibility was determined. Many participants and key informants identified the importance of counseling and the need to make an informed, independent choice on the timing of ART initiation, based on individual circumstances. Acceptance of ART-eligibility improved with time on the programme, however, as women's principal reason for initiating ART was protection of the unborn child, monitoring and supporting adherence during the post-partum period will be critical.

Pumping the brakes: rostromedial tegmental inhibition of compulsive cocaine seeking.

Addiction is marked by aberrant decision-making and an inability to suppress inappropriate and often dangerous behaviors. We previously demonstrated that inactivation of the rostromedial tegmental nucleus (RMTg) in rats causes persistent food seeking despite impending aversive footshock, an effect strikingly similar to the punishment resistance observed in people with a history of protracted drug use [1]. Here, we extend these studies to demonstrate chemogenetic silencing of RMTg axonal projections to the ventral tegmental area (VTA) (RMTg→VTA pathway) causes rats to endure significantly more footshock to receive cocaine infusions. To further test whether activation of this circuit is sufficient to suppress reward seeking in the absence of an overtly aversive stimulus, we used temporally specific optogenetic stimulation of the RMTg→VTA pathway as a "punisher" in place of footshock following lever pressing for either food or cocaine reward. While optical stimulation of the RMTg→VTA pathway robustly suppressed lever pressing for food, we found that stimulation of this circuit had only modest effects on suppressing responding for cocaine infusions. Even though optical RMTg→VTA stimulation was not particularly effective at reducing ongoing cocaine use, this experience nevertheless had long-lasting consequences, as reinstatement of drug seeking in response to cocaine-associated cues was profoundly suppressed when tested nearly two weeks later. These results suggest the RMTg may serve as a useful target for producing enduring reductions in drug craving, particularly during periods of abstinence from drug use.

Pilot programme for the rapid initiation of antiretroviral therapy in pregnancy in Cape Town, South Africa.

Initiation of antiretroviral therapy (ART) in pregnancy is an important intervention to prevent the mother-to-child transmission (MTCT) of HIV and to promote maternal health. Early initiation of ART is particularly important to achieve viral suppression rapidly before delivery. However, current approaches to start ART in pregnancy may be problematic in many settings, with referrals between antenatal care (ANC) and ART services, and delays for patient preparation before ART initiation. These steps contribute to a sizable proportion of women failing to receive adequate duration of ART before delivery, increasing the risk of MTCT. To address these limitations, we developed the rapid initiation of antiretroviral therapy in pregnancy (RAP) programme. The programme featured the use of point-of-care CD4 testing to identify ART-eligible women with CD4 cell counts ≤ 350 cells/µl; immediate ART initiation in women on the same day that eligibility was determined, if possible; and intensive counselling and support for ART initiation during the first few weeks on ART. We implemented RAP in an antenatal clinic setting in Cape Town South Africa. Between February and August 2011, a total of 221 HIV-infected women were referred to the programme for CD4 cell count testing and 101 (46%) were eligible for ART. Of these, 98 women (97%) started therapy during pregnancy, 89 (91%) on the day of referral to the service. In-depth interviews suggested that although there were substantial challenges facing HIV-infected women initiating ART in pregnancy, the availability of immediate services and counselling support played an important role in addressing these. While further research is needed, this evaluation demonstrates that a novel service delivery approach may facilitate rapid ART initiation in pregnancy.

An atlas of transcriptionally defined cell populations in the rat ventral tegmental area.

The ventral tegmental area (VTA) is a complex brain region that is essential for reward function and frequently implicated in neuropsychiatric disease. While decades of research on VTA function have focused on dopamine neurons, recent evidence has identified critical roles for GABAergic and glutamatergic neurons in reward processes. Additionally, although subsets of VTA neurons express genes involved in the synthesis and transport of multiple neurotransmitters, characterization of these combinatorial populations has largely relied on low-throughput methods. To comprehensively define the molecular architecture of the VTA, we performed single-nucleus RNA sequencing on 21,600 cells from the rat VTA. Analysis of neuronal subclusters identifies selective markers for dopamine and combinatorial neurons, reveals expression profiles for receptors targeted by drugs of abuse, and demonstrates population-specific enrichment of gene sets linked to brain disorders. These results highlight the heterogeneity of the VTA and provide a resource for further exploration of VTA gene expression.

Role of biomarkers in the diagnosis and prognosis of patients with cutaneous lupus erythematosus.

Cutaneous lupus erythematosus (CLE) is a connective tissue disease with varying presentations, and clinical sequelae including itching, dyspigmentation, and scarring. CLE can occur as its own entity or in conjunction with systemic disease, known as systemic lupus erythematosus (SLE). Because CLE is clinically diverse, identification of a biomarker may help not only facilitate early diagnosis and management but also identify individuals at risk for poor prognosis and development of SLE. While potential biomarkers in SLE have been extensively studied, few biomarkers for CLE have been identified and incorporated into clinical practice. Anti-SS-A antibody is a commonly used biomarker for diagnosis of subacute CLE patients. Type I interferon-related proteins such as MxA and guanylate binding protein-1 (GBP-1) and chemokines such as CXCR3, CXCL9, and CXCL10 have been identified as biomarkers that may support diagnosis and track disease activity. First-line oral treatment for CLE currently consists of anti-malarials such as hydroxychloroquine (HCQ), chloroquine (CQ), and quinacrine (QC). Studies have found that an increased myeloid dendritic cell population with higher TNF-α expression may be predictive of poor treatment response to HCQ in CLE patients. Autoantibodies against nuclear antigens (e.g., anti-double-stranded DNA and anti-Smith antibodies) and elevated erythrocyte sedimentation rate have been more commonly found in CLE patients progressing to SLE than those who have not. This review aims to summarize previous and emerging biomarkers for CLE patients.

Emerging treatments for scleroderma/systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs and has significant clinical sequelae. Management of SSc cutaneous disease remains challenging and often is driven by extracutaneous manifestations. Methotrexate is the typical first-line therapy for patients with early progressive cutaneous disease. However, in patients with diffuse progressive skin disease and inflammatory arthritis, methotrexate or rituximab monotherapy should be considered. First-line therapy for patients with concomitant myositis includes methotrexate or intravenous immunoglobulin (IVIG). For patients with both cutaneous findings and interstitial lung disease, studies have suggested the efficacy of mycophenolate mofetil or rituximab. Second-line therapies, including UVA-1 phototherapy, IVIG, or rituximab, can be considered in patients with disease refractory to first-line treatments. Clinical trials investigating the utility of emerging therapies such as abatacept and tocilizumab in the treatment of SSc are under way, and preliminary results are promising. Nonetheless, all patients with SSc benefit from a gentle skin-care regimen to alleviate pruritis, which is a commonly reported symptom. Additional cutaneous manifestations of SSc include telangiectasias, calcinosis cutis, microstomia, and Raynaud's phenomenon. Telangiectasia may be managed with camouflage techniques, pulse dye laser, and intense pulse light. Calcinosis cutis therapy is guided by the size of the calcium deposits, although treatment options are limited. Mouth augmentation and oral stretching exercises are recommended for patients with reduced oral aperture. Raynaud's phenomenon is treated with a combination of lifestyle modification and calcium channel blockers, such as amlodipine. Overall, SSc is a clinically heterogenous disease that affects multiple organ systems. Providers should assess extracutaneous involvement and use evidence-based recommendations to select the most appropriate therapy for patients with SSc.

The effects of anxiety on affective learning and serial position recall.

Sixty-five college-aged adults participated in a study that examined the effects of trait and state anxiety on learning positive and negative emotional words from the Affective Auditory Verbal Learning Test (AAVL). Self-reported state and trait anxiety were measured via Speilberger's State-Trait Anxiety Inventory (STAI). Each participant completed the five learning trials and delayed recall trial of the positive and negative word lists; order of administration for the word lists was counterbalanced across participants. Using ANOVA, initial analyses revealed significant effects for order of administration of the positive and negative word lists. ANCOVAs (using state and trait anxiety as covariates) yielded a significant interaction involving serial position, trial, and state anxiety as well as an interaction involving serial position, trial, and trait anxiety. Post hoc analyses did not support a priori hypotheses. However, state anxiety was associated with decreased word recall on the first learning trial. The results of this study indicate that state anxiety is initially associated with decreased performance when learning emotional words. However, these initial effects dissipate with subsequent learning trials. Implications for task performance are discussed.

Safety, feasibility and efficacy of a rapid ART initiation in pregnancy pilot programme in Cape Town, South Africa.

BACKGROUND: Antiretroviral therapy (ART) in pregnancy is a crucial intervention in the prevention of mother-to-child transmission (PMTCT) of HIV. It is recognised that mother-to-child transmission is reduced with each week on ART. However, in most South African settings, ART initiation is delayed owing to slow determination of treatment eligibility and separation of HIV and antenatal care services. OBJECTIVE: The rapid initiation of an ART in pregnancy programme is a model of care designed to expedite treatment initiation in ART- eligible pregnant women. This study evaluated the performance of the programme. METHODS: Participants enrolled in the ART programme in the same week as their first ANC visit throughout 2011, and had outcome data available by March 2012. Treatment eligibility was determined or confirmed via point-of-care CD4+ testing. Eligible women were offered ART immediately, with concurrent counselling and safety laboratory blood testing. Women attended until 6 - 8 weeks after delivery. Data were collected from clinical records with infant polymerase chain reaction (PCR) results at 6 weeks. RESULTS: Of 134 ART-eligible (CD4+ count <350 cells/µl or WHO stage III/IV) pregnant women, 130 (97.0%) started ART, 118 (90.8%) initiating treatment the same day that treatment eligibility was determined. There were no abnormal laboratory blood results or adverse events that required medical intervention. Pre-delivery retention in care and infant mortality were comparable to those in similar settings. Of the 107 pregnancies with PCR outcomes available, there was 1 positive HIV result in an infant (0.9%). Maternal viral load suppression in this mother was not achieved by the time of delivery. CONCLUSIONS: This pilot programme provides evidence that rapid ART initiation in pregnancy is safe, feasible and effective in reducing PMTCT. Further follow-up is required to monitor long-term outcomes.