Probability, cost, and interpretation biases' relationships with depressive and anxious symptom severity: differential mediation by worry and repetitive negative thinking.

People high in depressive or anxious symptom severity show repetitive negative thinking, including worry and rumination. They also show various cognitive phenomena, including probability, cost, and interpretation biases. Since there is conceptual overlap between these cognitive biases and repetitive negative thinking - all involve thinking about potential threats and misfortunes - we wondered whether repetitive negative thinking could account for (mediate) these cognitive biases' associations with depressive and anxious symptom severity. In three studies, conducted in two languages and cultures, cost bias and (in two studies) interpretation bias only predicted symptom severity via worry and repetitive negative thinking; this suggests these biases are actually associated with repetitive negative thinking, rather than with symptoms. In contrast, probability bias showed direct relationships with depressive (all studies) and anxious (two studies) symptom severity, suggesting its relationships with symptoms are partly independent of repetitive negative thinking. These results show the value of studying relationships among the various cognitive features of psychopathology. Furthermore, new interventions which target cognitive biases in depression or anxiety must show that they can improve upon cognitive behavioural therapy, which is already widely available, targets both repetitive negative thinking and probability bias, and is highly effective.

Paleoecology provides context for conserving culturally and ecologically important pine forest and barrens communities.

In fire-prone ecosystems, knowledge of vegetation-fire-climate relationships and the history of fire suppression and Indigenous cultural burning can inform discussions of how to use fire as a management tool, particularly as climate continues to change rapidly. On Wiisaakodewan-minis/Stockton Island in the Apostle Islands National Lakeshore of Wisconsin, USA, structural changes in a pine-dominated natural area containing a globally rare barrens community occurred after the cessation of cultural burning by the Indigenous Ojibwe people and the imposition of fire-suppression policies, leading to questions about the historical role of fire in this culturally and ecologically important area. To help understand better the ecological context needed to steward these pine forest and barrens communities, we developed palaeoecological records of vegetation, fire, and hydrological change using pollen, charcoal, and testate amoebae preserved in peat and sediment cores collected from bog and lagoon sediments within the pine-dominated landscape. Results indicated that fire has been an integral part of Stockton Island ecology for at least 6000 years. Logging in the early 1900s led to persistent changes in island vegetation, and post-logging fires of the 1920s and 1930s were anomalous in the context of the past millennium, likely reflecting more severe and/or extensive burning than in the past. Before that, the composition and structure of pine forest and barrens had changed little, perhaps due to regular low-severity surface fires, which may have occurred with a frequency consistent with Indigenous oral histories (~4-8 years). Higher severity fire episodes, indicated by large charcoal peaks above background levels in the records, occurred predominantly during droughts, suggesting that more frequent or more intense droughts in the future may increase fire frequency and severity. The persistence of pine forest and barrens vegetation through past periods of climatic change indicates considerable ecological resistance and resilience. Future persistence in the face of climate changes outside this historical range of variability may depend in part on returning fire to these systems.

Injection Drug Use and Sexual Risk Behaviors Among People who Inject Drugs in Ukraine: A Random-Intercept Latent Transition Analysis.

HIV transmission in Ukraine is driven in part by unsafe injection drug use and sexual risk behaviors among people who inject drugs. We performed a random-intercept latent transition analysis on responses to 9 binary injection drug use and sexual behavior items from 1195 people who inject drugs with negative HIV status enrolled in a clustered randomized clinical trial of a social network intervention in Odessa, Donetsk, and Nikolayev, Ukraine. We identified 5 baseline classes: "Social injection/equipment-sharing" (11.7%), "Social injection" (25.9%), "High-risk collective preparation/splitting" (17.0%), "Collective preparation/splitting" (11.3%), and "Dealer-facilitated injection" (34.1%). After 12 months, intervention participants were more likely to transition to the "Collective preparation/splitting" class, which featured the fewest risk behaviors. Transitioning from the "Collective preparation/splitting" to the "Social injection/equipment-sharing" class was associated with HIV acquisition for control participants. Research to illuminate the stability of these patterns and how they may benefit from uniquely tailored programming to reduce unsafe behaviors is needed.

Cathepsin S Contributes to Lung Inflammation in Acute Respiratory Distress Syndrome.

Rationale: Although the cysteine protease cathepsin S has been implicated in the pathogenesis of several inflammatory lung diseases, its role has not been examined in the context of acute respiratory distress syndrome, a condition that still lacks specific and effective pharmacological treatments. Objectives: To characterize the status of cathepsin S in acute lung inflammation and examine the role of cathepsin S in disease pathogenesis. Methods: Human and mouse model BAL fluid samples were analyzed for the presence and activity of cathepsin S and its endogenous inhibitors. Recombinant cathepsin S was instilled directly into the lungs of mice. The effects of cathepsin S knockout and pharmacological inhibition were examined in two models of acute lung injury. Protease-activated receptor-1 antagonism was used to test a possible mechanism for cathepsin S-mediated inflammation. Measurements and Main Results: Pulmonary cathepsin S concentrations and activity were elevated in acute respiratory distress syndrome, a phenotype possibly exacerbated by the loss of the endogenous antiprotease cystatin SN. Direct cathepsin S instillation into the lungs induced key pathologies of acute respiratory distress syndrome, including neutrophilia and alveolar leakage. Conversely, in murine models of acute lung injury, genetic knockdown and prophylactic or therapeutic inhibition of cathepsin S reduced neutrophil recruitment and protein leakage. Cathepsin S may partly mediate its pathogenic effects via protease-activated receptor-1, because antagonism of this receptor abrogated cathepsin S-induced airway inflammation. Conclusions: Cathepsin S contributes to acute lung injury and may represent a novel therapeutic target for acute respiratory distress syndrome.

Effects of a social network intervention on HIV seroconversion among people who inject drugs in Ukraine: moderation by network gender composition.

BACKGROUND: Women who inject drugs in Ukraine are disproportionately burdened by HIV. To help address the needs of this population, a greater understanding of how interventions may uniquely benefit women who inject drugs is needed. METHODS: Data come from a randomized controlled trial of a social network intervention targeting people who inject drugs in Ukraine (N = 1195). Indexes, plus two of their injection network members, received HIV testing and counseling (control arm) or HIV testing and counseling plus a social network intervention (intervention arm), in which indexes were trained to influence network members' risk behaviors. We used Cox regressions with interaction terms to assess differences in time to HIV seroconversion between arms by network gender composition and gender of the index. For significant interaction terms, we calculated simple effects, generated survival functions using Kaplan-Meier methods, and compared survival curves using log-rank tests. RESULTS: At 12 months, there were 45 seroconversions among women (40.0 [28.3, 51.7] per 100 person years) and 111 among men (28.4 [23.1, 33.6] per 100 person years) in the control arm; there were 27 seroconversions among women (17.1 [10.7, 23.6] per 100 person years) and 77 among men (18.7 [14.5, 22.9] per 100 person years) in the intervention arm. Network gender composition (but not gender of the index) moderated the intervention effect on HIV incidence (p < 0.05). Specifically, the intervention appeared to be even more protective against HIV acquisition as female gender composition increased. In the intervention arm, the HIV seroconversion hazard rate was 44% lower with 1 network female; 61% lower with 2 network females; and 72% lower with 3 network females. CONCLUSIONS: A greater number of women in an injection network, coupled with the provision of risk-reduction strategies, is associated with HIV risk-mitigation, though the mechanisms through which this occurs remain unclear. Findings can support new research and practice directions that prioritize women who inject drugs and more thoughtfully support their health and wellbeing.

A Francisella tularensis L,D-carboxypeptidase plays important roles in cell morphology, envelope integrity, and virulence.

Francisella tularensis is a Gram-negative, intracellular bacterium that causes the zoonotic disease tularemia. Intracellular pathogens, including F. tularensis, have evolved mechanisms to survive in the harsh environment of macrophages and neutrophils, where they are exposed to cell envelope-damaging molecules. The bacterial cell wall, primarily composed of peptidoglycan (PG), maintains cell morphology, structure, and membrane integrity. Intracellular Gram-negative bacteria protect themselves from macrophage and neutrophil killing by recycling and repairing damaged PG--a process that involves over 50 different PG synthesis and recycling enzymes. Here, we identified a PG recycling enzyme, L,D-carboxypeptidase A (LdcA), of F. tularensis that is responsible for converting PG tetrapeptide stems to tripeptide stems. Unlike E. coli LdcA and most other orthologs, F. tularensis LdcA does not localize to the cytoplasm and also exhibits L,D-endopeptidase activity, converting PG pentapeptide stems to tripeptide stems. Loss of F. tularensis LdcA led to altered cell morphology and membrane integrity, as well as attenuation in a mouse pulmonary infection model and in primary and immortalized macrophages. Finally, an F. tularensis ldcA mutant protected mice against virulent Type A F. tularensis SchuS4 pulmonary challenge.

Contextuality and Wigner Negativity Are Equivalent for Continuous-Variable Quantum Measurements.

Quantum computers promise considerable speedups with respect to their classical counterparts. However, the identification of the innately quantum features that enable these speedups is challenging. In the continuous-variable setting-a promising paradigm for the realization of universal, scalable, and fault-tolerant quantum computing-contextuality and Wigner negativity have been perceived as two such distinct resources. Here we show that they are in fact equivalent for the standard models of continuous-variable quantum computing. While our results provide a unifying picture of continuous-variable resources for quantum speedup, they also pave the way toward practical demonstrations of continuous-variable contextuality and shed light on the significance of negative probabilities in phase-space descriptions of quantum mechanics.

Estimated probabilities of positive, vs. negative, events show separable correlations with COVID-19 preventive behaviours.

Research has associated optimism with better health-protective behaviours, but few studies have measured optimism or pessimism directly, by asking participants to estimate probabilities of events. We used these probability estimates to examine how optimism and/or pessimism relate to protecting oneself from COVID-19. When COVID-19 first reached Turkey, we asked a snowball sample of 494 Istanbul adults how much they engaged in various COVID-protective behaviours. They also estimated the probabilities of their catching COVID-19, and of other positive and negative events happening to them. Estimated probability of general positive events (optimism) correlated positively with officially-recommended helpful behaviours (e.g. wearing masks), but not with less-helpful behaviours (e.g. sharing 'alternative' COVID-related information online). Estimated probabilities of general negative events (pessimism), or of catching COVID, did not correlate significantly with helpful COVID-related behaviours; but they did correlate with psychopathological symptoms, as did less-helpful COVID-related behaviours. This shows important nuances can be revealed by measuring optimism and pessimism, as separate variables, using probability estimates.

Assessing Potential Outcomes Mediation in HIV Interventions.

Knowledge of causal processes through mediation analysis can help improve the effectiveness and reduce costs of public health programs, like HIV prevention and treatment interventions. Advancements in mediation using the potential outcomes framework provide a method for estimating the causal effect of interventions on outcomes via a mediating variable. The purpose of this paper is to provide practical information about mediation and the potential outcomes framework that can enhance data analysis and causal inference for intervention studies. Causal mediation effects are defined and then estimated using data from an HIV intervention randomized trial among people who inject drugs (PWID) in Ukraine. Results from a potential outcomes mediation analysis show that the intervention had a total causal effect on incident HIV infection such that participants in the experimental group were 36% less likely to become infected during the 12-month study than those in the control arm, but that neither self-efficacy nor network communication mediated this effect. Because neither putative mediator was significant, measurement and confounding issues should be investigated to rule out these mediators. Other putative mediators, such as injection frequency, route of administration, or HIV knowledge can be considered. Future research is underway to examine additional, multiple mediators explaining efficacy of the current intervention and sensitivity to confounding effects.

Therapeutic Inhibition of Cathepsin S Reduces Inflammation and Mucus Plugging in Adult ßENaC-Tg Mice.

BACKGROUND: Elevated levels of the cysteine protease cathepsin S (CatS) are associated with chronic mucoobstructive lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). We have previously demonstrated that prophylactic treatment with a CatS inhibitor from birth reduces inflammation, mucus plugging, and lung tissue damage in juvenile ß-epithelial Na+ channel-overexpressing transgenic (ßENaC-Tg) mice with chronic inflammatory mucoobstructive lung disease. In this study, we build upon this work to examine the effects of therapeutic intervention with a CatS inhibitor in adult ßENaC-Tg mice with established disease. METHODS: ßENaC-Tg mice and wild-type (WT) littermates were treated with a CatS inhibitor from 4 to 6 weeks of age, and CatS-/- ßENaC-Tg mice were analysed at 6 weeks of age. Bronchoalveolar lavage (BAL) fluid inflammatory cell counts were quantified, and lung tissue destruction and mucus obstruction were analysed histologically. RESULTS: At 6 weeks of age, ßENaC-Tg mice developed significant airway inflammation, lung tissue damage, and mucus plugging when compared to WT mice. CatS-/- ßENaC-Tg mice and ßENaC-Tg mice receiving inhibitor had significantly reduced airway mononuclear and polymorphonuclear (PMN) cell counts as well as mucus plugging. However, in contrast to CatS-/- ßENaC-Tg mice, therapeutic inhibition of CatS in ßENaC-Tg mice had no effect on established emphysema-like lung tissue damage. CONCLUSIONS: These results suggest that while early CatS targeting may be required to prevent the onset and progression of lung tissue damage, therapeutic CatS targeting effectively inhibited airway inflammation and mucus obstruction. These results indicate the important role CatS may play in the pathogenesis and progression of mucoobstructive lung disease.

Attentional control and estimation of the probability of positive and negative events.

People high in negative affect tend to think negative events are more likely than positive events ("probability bias"). Studies have found that weak attentional control exaggerates another negative affect-related cognitive bias - attentional bias - but it is not clear why this might be. We therefore wanted to know whether weak attentional control would be related to probability bias too. Four studies, with predominantly female student samples (N = 857), revealed correlations of around -.38 between attentional control and probability bias. This remained significant when trait anxiety and depression were controlled; there were no interactions between attentional control and negative affect. Studies 3 and 4 found that attentional control's relationship with probability bias was partly mediated by emotion regulation ability. These results suggest attentional control is important for regulating affect-related cognitive biases, and for emotion regulation in general. Furthermore, because cognitive biases are thought to be important for maintaining emotional disorders, these results are also consistent with weak attentional control being a risk factor for these disorders.

Targeting of cathepsin S reduces cystic fibrosis-like lung disease.

Cathepsin S (CatS) is upregulated in the lungs of patients with cystic fibrosis (CF). However, its role in CF lung disease pathogenesis remains unclear.In this study, ß-epithelial Na+ channel-overexpressing transgenic (ßENaC-Tg) mice, a model of CF-like lung disease, were crossed with CatS null (CatS-/-) mice or treated with the CatS inhibitor VBY-999.Levels of active CatS were elevated in the lungs of ßENaC-Tg mice compared with wild-type (WT) littermates. CatS-/-ßENaC-Tg mice exhibited decreased pulmonary inflammation, mucus obstruction and structural lung damage compared with ßENaC-Tg mice. Pharmacological inhibition of CatS resulted in a significant decrease in pulmonary inflammation, lung damage and mucus plugging in the lungs of ßENaC-Tg mice. In addition, instillation of CatS into the lungs of WT mice resulted in inflammation, lung remodelling and upregulation of mucin expression. Inhibition of the CatS target, protease-activated receptor 2 (PAR2), in ßENaC-Tg mice resulted in a reduction in airway inflammation and mucin expression, indicating a role for this receptor in CatS-induced lung pathology.Our data indicate an important role for CatS in the pathogenesis of CF-like lung disease mediated in part by PAR2 and highlight CatS as a therapeutic target.

Interventions to Reduce Drug Use Among Methamphetamine Users at Risk for HIV.

PURPOSE OF REVIEW: This paper reports on the results of a study comparing two behavioral treatments for methamphetamine users. The outcome was the effectiveness of the interventions in reducing meth use. The interventions were contingency management (CM) and contingency management plus strengths-based case management (CM/SBCM). RECENT FINDINGS: CM/SBCM was found to be associated with attending more sessions for people who reported being in a couple. Also, participants who earned more money in the first part of the study were more likely to have more clean urinalysis in the second part of the study. Latent class analysis identified a class of participants who were in a couple, without sexual abuse history, and less meth use at baseline. This class tended to have more clean urinalysis in the CM/SBCM intervention. These results indicate that incentive-based interventions with case management may be useful for helping meth users reduce their drug use.

Geometrical Bounds on Irreversibility in Open Quantum Systems.

The Clausius inequality has deep implications for reversibility and the arrow of time. Quantum theory is able to extend this result for closed systems by inspecting the trajectory of the density matrix on its manifold. Here we show that this approach can provide an upper and lower bound to the irreversible entropy production for open quantum systems as well. These provide insights on how the information on the initial state is forgotten through a thermalization process. Limits of the applicability of our bounds are discussed and demonstrated in a quantum photonic simulator.

The perfect storm: incarceration and the high-risk environment perpetuating transmission of HIV, hepatitis C virus, and tuberculosis in Eastern Europe and Central Asia.

Despite global reductions in HIV incidence and mortality, the 15 UNAIDS-designated countries of Eastern Europe and Central Asia (EECA) that gained independence from the Soviet Union in 1991 constitute the only region where both continue to rise. HIV transmission in EECA is fuelled primarily by injection of opioids, with harsh criminalisation of drug use that has resulted in extraordinarily high levels of incarceration. Consequently, people who inject drugs, including those with HIV, hepatitis C virus, and tuberculosis, are concentrated within prisons. Evidence-based primary and secondary prevention of HIV using opioid agonist therapies such as methadone and buprenorphine is available in prisons in only a handful of EECA countries (methadone or buprenorphine in five countries and needle and syringe programmes in three countries), with none of them meeting recommended coverage levels. Similarly, antiretroviral therapy coverage, especially among people who inject drugs, is markedly under-scaled. Russia completely bans opioid agonist therapies and does not support needle and syringe programmes-with neither available in prisons-despite the country's high incarceration rate and having the largest burden of people with HIV who inject drugs in the region. Mathematical modelling for Ukraine suggests that high levels of incarceration in EECA countries facilitate HIV transmission among people who inject drugs, with 28-55% of all new HIV infections over the next 15 years predicted to be attributable to heightened HIV transmission risk among currently or previously incarcerated people who inject drugs. Scaling up of opioid agonist therapies within prisons and maintaining treatment after release would yield the greatest HIV transmission reduction in people who inject drugs. Additional analyses also suggest that at least 6% of all incident tuberculosis cases, and 75% of incident tuberculosis cases in people who inject drugs are due to incarceration. Interventions that reduce incarceration itself and effectively intervene with prisoners to screen, diagnose, and treat addiction and HIV, hepatitis C virus, and tuberculosis are urgently needed to stem the multiple overlapping epidemics concentrated in prisons.

A Hazard Analysis of Risk Factors of Mortality in Individuals Who Inject Drugs in Denver CO.

Despite multiple risk factors for mortality among People Who Inject Drugs (PWID), more research is warranted that examines sub-populations within PWID. Mortality data from PWID participating in longitudinal HIV prevention research in Denver were obtained from The Colorado Department of Public Health and Environment. Risk factors for both all-cause and acute-toxicity related mortality were analyzed using Cox proportional hazards regression. Two-thousand seven individuals were interviewed at baseline. Eighty-six individuals died during the time frame of the study, 58 of which were due to acute-toxicity. Disabled (HR = 3.3, p < 0.001), gay/lesbian-identified (HR = 2.6, p = 0.03), white race/ethnicity (HR = 2.4, p = 0.003), and use of a shared cooker (HR = 2.1, p = 0.01) were important adjusted risk factors. These suggest that drug and HIV interventions should utilize techniques that can address the needs of marginalized populations in addition to HIV drug risk behaviors.

State anxiety impairs attentional control when other sources of control are minimal.

Research suggests anxiety impairs attentional control; however, this effect has been unreliable. We argue that anxiety's impairment of attentional control is subtle, and can be obscured by other non-emotional sources of control. We demonstrate this by examining conflict adaptation, an enhancement in attentional control following a trial with high conflict between distracter and target stimuli. Participants completed a Stroop task featuring incongruent (e.g. RED in green font; high-conflict) and control (e.g. +++ in green font; low-conflict) trials. More state-anxious participants showed greater Stroop interference following control trials, but interference was uniformly low following incongruent trials. This suggests state anxiety can impair attention, but other sources of top-down control - such as conflict adaptation - can easily overcome this impairment. This is consistent with recent theories of anxious cognition and shows that anxiety researchers must attend to the dynamics and sources of attentional control.

Krokodile Injectors in Ukraine: Fueling the HIV Epidemic?

This study was designed to assess the characteristics of krokodile injectors, a recent phenomenon in Ukraine, and HIV-related risk factors among people who inject drugs (PWID). In three Ukraine cities, Odessa, Donetsk and Nikolayev, 550 PWID were recruited between December 2012 and October 2013 using modified targeted sampling methods. The sample averaged 31 years of age and they had been injecting for over 12 years. Overall, 39 % tested positive for HIV, including 45 % of krokodile injectors. In the past 30 days, 25 % reported injecting krokodile. Those who injected krokodile injected more frequently (p < 0.001) and they injected more often with others (p = 0.005). Despite knowing their HIV status to be positive, krokodile users did not reduce their injection frequency, indeed, they injected as much as 85 % (p = 0.016) more frequently than those who did not know their HIV status or thought they were negative. This behavior was not seen in non-krokodile using PWID. Although only a small sample of knowledgeable HIV positive krokodile users was available (N = 12), this suggests that krokodile users may disregard their HIV status more so than nonkrokodile users. In spite of widespread knowledge of its harmful physical consequences, a growing number of PWID are turning to injecting krokodile in Ukraine. Given the recency of krokodile use the country, the associated higher frequency of injecting, a propensity to inject more often with others, and what could be a unique level of disregard of HIV among krokodile users, HIV incidence could increase in future years.

Looking good or doing good? Motivations for organisational citizenship behaviour in Turkish versus South Korean collectivists.

The purpose of this article is to explore potential motivations to perform organisational citizenship behaviour (OCB) in collectivistic Turkish and South Korean societies. Although collectivism has been proposed as a predictor of OCB, previous research has not fully explored the possibility that collectivistic individuals' OCB may result from their self-oriented motives (i.e. social desirability concerns) or their future-oriented motives (i.e. long-term orientation concerns). We predicted that OCB stems from social desirability concerns among Turkish collectivists, meaning it is used for maintaining a positive image within the organisation. However, for South Korean collectivists, we predicted that OCB stems from their long-term orientation concerns, meaning it is used to make the organisation better. The results were in line with our predictions, and the findings are discussed in terms of their implications for firms in collectivistic societies.