Fast odour dynamics are encoded in the olfactory system and guide behaviour.

Odours are transported in turbulent plumes, which result in rapid concentration fluctuations1,2 that contain rich information about the olfactory scenery, such as the composition and location of an odour source2-4. However, it is unclear whether the mammalian olfactory system can use the underlying temporal structure to extract information about the environment. Here we show that ten-millisecond odour pulse patterns produce distinct responses in olfactory receptor neurons. In operant conditioning experiments, mice discriminated temporal correlations of rapidly fluctuating odours at frequencies of up to 40 Hz. In imaging and electrophysiological recordings, such correlation information could be readily extracted from the activity of mitral and tufted cells-the output neurons of the olfactory bulb. Furthermore, temporal correlation of odour concentrations5 reliably predicted whether odorants emerged from the same or different sources in naturalistic environments with complex airflow. Experiments in which mice were trained on such tasks and probed using synthetic correlated stimuli at different frequencies suggest that mice can use the temporal structure of odours to extract information about space. Thus, the mammalian olfactory system has access to unexpectedly fast temporal features in odour stimuli. This endows animals with the capacity to overcome key behavioural challenges such as odour source separation5, figure-ground segregation6 and odour localization7 by extracting information about space from temporal odour dynamics.

Wireless monitoring of respiration with EEG reveals relationships between respiration, behavior, and brain activity in freely moving mice.

Active sampling in the olfactory domain is a fundamental aspect of mouse behavior, and there is increasing evidence that respiration-entrained neural activity outside of the olfactory system sets an important global brain rhythm. It is therefore crucial to accurately measure breathing during natural behaviors. We develop a new approach to do this in freely moving animals, by implanting a telemetry-based pressure sensor into the right jugular vein, which allows for wireless monitoring of thoracic pressure. After verifying this technique against standard head-fixed respiration measurements, we combined it with EEG and EMG recording and used evolving partial coherence analysis to investigate the relationship between respiration and brain activity across a range of experiments in which the mice could move freely. During voluntary exploration of odors and objects, we found that the association between respiration and cortical activity in the delta and theta frequency range decreased, whereas the association between respiration and cortical activity in the alpha range increased. During sleep, however, the presentation of an odor was able to cause a transient increase in sniffing without changing dominant sleep rhythms (delta and theta) in the cortex. Our data align with the emerging idea that the respiration rhythm could act as a synchronizing scaffold for specific brain rhythms during wakefulness and exploration, but suggest that respiratory changes are less able to impact brain activity during sleep. Combining wireless respiration monitoring with different types of brain recording across a variety of behaviors will further increase our understanding of the important links between active sampling, passive respiration, and neural activity.NEW & NOTEWORTHY Animals can alter their respiration rate to actively sample their environment, and increasing evidence suggests that neurons across the brain align their firing to this changing rhythm. We developed a new approach to measure sniffing in freely moving mice while simultaneously recording brain activity, and uncovered how specific cortical rhythms changed their coherence with respiration rhythm during natural behaviors and across arousal states.

Parent and staff experiences of a feasibility trial evaluating neurally adjusted ventilatory assist in infants with acute viral bronchiolitis: A qualitative study.

BACKGROUND: There is limited literature regarding family and staff experiences of participating in clinical trials. A qualitative study was embedded in the NAVABronch feasibility trial evaluating the effectiveness of a novel mode of ventilation, neurally adjusted ventilatory assist (NAVA), in infants with acute viral bronchiolitis. AIM: The aim of this qualitative study was to explore the experiences of parents and health care practitioners (HCPs) involved in the NAVABronch Trial. STUDY DESIGN: Semi-structured interviews were conducted with two parents and two focus groups were held with six HCPs. RESULTS: Four themes were identified from the focus groups: (1) Creating staff engagement, (2) Education to deliver NAVA, (3) Normalizing NAVA in clinical practice (4) Creating meaningful study outcomes and (5) support of parents during the trial, this theme was generated from the parent interviews. The findings indicated the need for education regarding NAVA for HCPs which would lead to increased confidence, better guidance around the use of NAVA and the need for NAVA to be normalized and embedded into the unit culture. Parents identified the need for further support around preparation for what may happen as a result of the interventions, particularly the weaning of sedation. CONCLUSION: Our study indicates that staff and parents had no concerns regarding the trial methods and procedures. RELEVANCE TO CLINICAL PRACTICE: Conducting clinical trials in Paediatric Intensive Care Units (PICUs) is challenging and complex. There is limited literature regarding family and staff experiences of participating in clinical trials. Understanding their experiences is crucial in ensuring trial success.

Belimumab use during pregnancy: a summary of birth defects and pregnancy loss from belimumab clinical trials, a pregnancy registry and postmarketing reports.

OBJECTIVE: Describe available data on birth defects and pregnancy loss in women with systemic lupus erythematosus (SLE) exposed to belimumab. METHODS: Data collected from belimumab clinical trials, the Belimumab Pregnancy Registry (BPR), and postmarketing/spontaneous reports up to 8 March 2020 were described. Belimumab exposure timing, concomitant medications and potential confounding factors were summarised descriptively. RESULTS: Among 319 pregnancies with known outcomes (excluding elective terminations), 223 ended in live births from which birth defects were identified in 4/72 (5.6%) in belimumab-exposed pregnancies and 0/9 placebo-exposed pregnancies across 18 clinical trials, 10/46 (21.7%) belimumab-exposed pregnancies in the BPR prospective cohort (enrolled prior to pregnancy outcome) and 0/4 belimumab-exposed pregnancies in the BPR retrospective cohort (enrolled after pregnancy outcome), and 1/92 (1.1%) in belimumab-exposed pregnancies from postmarketing/spontaneous reports. There was no consistent pattern of birth defects across datasets. Out of pregnancies with known outcomes (excluding elective terminations), pregnancy loss occurred in 31.8% (35/110) of belimumab-exposed women and 43.8% (7/16) of placebo-exposed women in clinical trials; 4.2% (2/48) of women in the BPR prospective cohort and 50% (4/8) in the BPR retrospective cohort; and 31.4% (43/137) of belimumab-exposed women from postmarketing/spontaneous reports. All belimumab-exposed women in clinical trials and the BPR received concomitant medications and had confounding factors and/or missing data. CONCLUSIONS: Observations reported here add to limited data published on pregnancy outcomes following belimumab exposure. Low numbers of exposed pregnancies, presence of confounding factors/other biases, and incomplete information preclude informed recommendations regarding risk of birth defects and pregnancy loss with belimumab use.

Racial Differences in the Association Between Alcohol Drinking and Cigarette Smoking: Preliminary Findings From an Alcohol Research Program.

AIMS: Important differences have been shown in alcohol drinking and cigarette smoking prevalence, patterns and consequences among individuals from different racial backgrounds. Alcohol and nicotine are often co-used, and the association between drinking and smoking may differ between racial groups-a question explored in the present study. METHODS: Data from the NIAAA natural history and screening protocols were utilized; non-Hispanic Black and non-Hispanic White individuals were included in the analyses [N = 1692; 65.2% male; 58.3% met criteria for current alcohol use disorder (AUD); 37.8% were current cigarette smokers]. Bivariate associations between assessments related to alcohol drinking and cigarette smoking were examined, and the strength and direction of these associations were compared between the two groups. RESULTS: The sample included 796 Black and 896 White individuals. Black participants had higher frequency (P < 0.0001) and severity (P = 0.007) of AUD, as well as higher frequency (P < 0.0001) of cigarette smoking. Bivariate analyses showed that the expected positive associations between alcohol drinking and cigarette smoking, observed among White individuals, were blunted or absent among Black individuals [age at first cigarette-AUD identification test (AUDIT) score: F(1, 292) = 7.60, P = 0.006; cigarette pack years-AUDIT score: F(1, 1111) = 10.97, P = 0.001]. CONCLUSIONS: Some decoupling in the association between alcohol drinking and cigarette smoking was found among Black compared to White individuals. The sample was drawn from a specific population enrolled in alcohol research protocols, which is a limitation of the present study. These preliminary findings highlight the importance of considering racial/ethnic background in preventive and therapeutic strategies for comorbid alcohol and nicotine use.

Impact of prolonged PPE use on Canadian health professionals.

AIM: To explore the impact that prolonged use of personal protective equipment (PPE) has on the skin integrity of Canadian health professionals. METHOD: A descriptive, pan-Canadian, cross-sectional, online survey was carried out to explore the type and prevalence of PPE-related skin injury among Canadian health professionals. Convenience sampling was used to disseminate the online survey link to health professionals. RESULTS: There were responses from 757 health professionals. Masks worn included surgical masks (90%), a combination of surgical or N95/KN95 masks (7.7%) and an N95/KN95 mask alone (2.7%). Responses showed 84.6% of providers always wear a mask while at work with 38.5% wearing the same mask all shift; 90% of participants wore protective eye wear. Complications included soreness or pressure injuries behind the ears (70%), new or worsening acne (52%), a runny nose or sneezing (45%), itching (39%), and dry skin (37%). Hand issues included dry skin (53%), red skin (30%), itching (26%), broken skin (20%), rash (16%), and dermatitis (11%) - 51% of respondents did not moisturise their hands. Complications related to gown use included itching (6%), moisture-associated skin damage (5.5%), feeling claustrophobic (4.5%), and new or worsening acne (3%). Increased perspiration due to PPE was experienced in 87.5% of respondents. Some 43% of respondents noted their mental health became worse due to wearing PPE for prolonged periods. CONCLUSION: These findings should be used in the development of guidelines to prevent and manage PPE-related skin injuries among health professionals. Education for professionals should focus on skin protection, prevention of PPE-related skin complications and support for mental health issues.

Psychometric evaluation of the Suicide Cognitions Scale-Revised (SCS-R).

The measurement of self-reported suicide risk can be complicated in medical settings due to patient apprehension about the potential consequences of self-disclosure. The Suicide Cognitions Scale (SCS) was designed to assess suicide risk by measuring a range of suicidogenic cognitions (e.g., hopelessness, perceived burdensomeness) collectively referred to as the suicidal belief system. The SCS's concurrent, known groups, and prospective validity for suicidal thoughts and behaviors have previously been supported. The present study examined the factor structure, known-groups, and concurrent validity of a revised, 16-item version of the SCS (SCS-R), which removed two items that explicitly used the word "suicide" and changed item scoring from a 1-5 to 0-4 scale, thereby improving the interpretation of scores. In a sample of 2,690 primary care patients presenting for routine medical care at one of six US military clinics, results of bifactor analysis supported the scale's unidimensionality. The SCS-R significantly differentiated participants with a history of suicide attempts and was significantly correlated with frequency of thoughts about death and self-harm during the previous 2 weeks. Results align with earlier research and provide psychometric support for the SCS-R.

Blood metabolomics in infants enrolled in a dose escalation pilot trial of budesonide in surfactant.

BACKGROUND: The pathogenesis of BPD includes inflammation and oxidative stress in the immature lung. Corticosteroids improve respiratory status and outcome, but the optimal treatment regimen for benefit with low systemic effects is uncertain. METHODS: In a pilot dose escalation trial, we administered ≤5 daily doses of budesonide in surfactant to 24 intubated premature infants (Steroid And Surfactant in ELGANs (SASSIE)). Untargeted metabolomics was performed on dried blood spots using UPLC-MS/MS. Tracheal aspirate IL-8 concentration was determined as a measure of lung inflammation. RESULTS: Metabolomics data for 829 biochemicals were obtained on 121 blood samples over 96 h from 23 infants receiving 0.025, 0.05, or 0.1 mg budesonide/kg. Ninety metabolites were increased or decreased in a time- and dose-dependent manner at q ≤ 0.1 with overrepresentation in lipid and amino acid super pathways. Different dose response patterns occurred, with negative regulation associated with highest sensitivity to budesonide. Baseline levels of 22 regulated biochemicals correlated with lung inflammation (IL-8), with highest significance for sphingosine and thiamin. CONCLUSIONS: Numerous metabolic pathways are regulated in a dose-dependent manner by glucocorticoids, which apparently act via distinct mechanisms that impact dose sensitivity. The findings identify candidate blood biochemicals as biomarkers of lung inflammation and systemic responses to corticosteroids. IMPACT: Treatment of premature infants in respiratory failure with 0.1 mg/kg intra-tracheal budesonide in surfactant alters levels of ~11% of detected blood biochemicals in discrete time- and dose-dependent patterns. A subset of glucocorticoid-regulated biochemicals is associated with lung inflammatory status as assessed by lung fluid cytokine concentration. Lower doses of budesonide in surfactant than currently used may provide adequate anti-inflammatory responses in the lung with fewer systemic effects, improving the benefit:risk ratio.

Improving Suicide Risk Screening to Identify the Highest Risk Patients: Results From the PRImary Care Screening Methods (PRISM) Study.

PURPOSE: Over 95% of patients who screen positive on the Patient Health Questionnaire-9 (PHQ-9) suicide risk item do not attempt or die by suicide, which could lead to unnecessary treatment and/or misallocation of limited resources. The present study seeks to determine if suicide risk screening can be meaningfully improved to identify the highest-risk patients. METHODS: Patients eligible to receive medical treatment from the US Department of Defense medical system were recruited from 6 military primary care clinics located at 5 military installations around the United States. Patients completed self-report measures including the PHQ-9 and 16 items from the Suicide Cognitions Scale (SCS) during routine primary care clinic visits. Postbaseline suicidal behaviors (suicide attempts, interrupted attempts, and aborted attempts) were assessed by evaluators who were blind to screening results using the Self-Injurious Thoughts and Behaviors Interview. RESULTS: Among 2,744 patients, 13 (0.5%) engaged in suicidal behavior in the 30 days after screening and 28 (1.0%) displayed suicidal behavior in the 90 days after screening. Multiple SCS items differentiated patients with suicidal behavior less than 30 days after screening positive for suicide risk. Augmenting the PHQ-9 suicide risk item with SCS items improved the identification of patients who were most likely to have suicidal behavior within a month of screening positive without sacrificing sensitivity. CONCLUSION: Among primary care patients who screen positive for suicide risk on the PHQ-9, SCS items improved screening efficiency by identifying those patients who are most likely to engage in suicidal behavior within the next 30 days.

Neurally Adjusted Ventilator Assist in Infants With Acute Respiratory Failure: A Literature Scoping Review.

OBJECTIVES: To map the evidence for neurally adjusted ventilatory assist strategies, outcome measures, and sedation practices in infants less than 12 months with acute respiratory failure using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidance. DATA SOURCES: CINAHL, MEDLINE, COCHRANE, JBI, EMBASE, PsycINFO, Google scholar, BNI, AMED. Trial registers included the following: ClinicalTrials.gov, European Union clinical trials register, International Standardized Randomized Controlled Trial Number register. Also included were Ethos, Grey literature, Google, dissertation abstracts, EMBASE conference proceedings. STUDY SELECTION: Abstracts were screened followed by review of full text. Articles incorporating a heterogeneous population of both infants and older children were assessed, and where possible, data for infants were extracted. Fifteen articles were included. Ten articles were primary research: randomized controlled trial (n = 3), cohort studies (n = 4), retrospective data analysis (n = 2), case series (n = 1). Other articles are expert opinion (n = 2), neurally adjusted ventilatory assist updates (n = 1), and a literature review (n = 2). Three studies included exclusively infants. We also included 12 studies reporting jointly on infants and children. DATA EXTRACTION: A standardized data extraction tool was used. DATA SYNTHESIS: Key findings were that evidence related to neurally adjusted ventilatory assist ventilation strategies in infants and related to specific primary conditions is limited. The setting of neurally adjusted ventilatory assist level is not consistent, and how to optimize this mode of ventilation was not documented. Outcome measures varied considerably, most studies focused on improvements in respiratory and physiological variables. Sedation use is variable with regard to medication type and dose. There is an indication that less sedation is required in patients receiving neurally adjusted ventilatory assist, but no conclusive evidence to support this. CONCLUSIONS: This review highlights a lack of standardized strategies for neurally adjusted ventilatory assist ventilation and sedation practices among infants with acute respiratory failure. Studies were limited by small sample sizes and a lack of focus on specific patient groups. Robust studies are needed to provide evidence-based clinical recommendations for the use of neurally adjusted ventilatory assist in infants with acute respiratory failure.

Treating Veterans at Risk for Suicide: An Examination of the Safety, Tolerability, and Outcomes of Cognitive Processing Therapy.

Individuals with posttraumatic stress disorder (PTSD) are at increased risk for suicidal thoughts and behaviors; however, clinicians often report apprehension about recommending trauma-focused therapy to patients with an increased risk of suicide. The present study aimed to evaluate the safety, tolerability, and response to cognitive processing therapy (CPT) among a sample of military veterans with PTSD and increased suicide risk. A secondary aim was to provide a clinically useful definition of high suicide risk. Chart review was used to classify the suicide risk level of 290 veterans who participated in CPT at a Veterans Affairs clinic. Treatment outcomes in veterans with different suicide risk levels were also gathered and compared. Over 50% (n = 155) of the sample demonstrated increased suicide risk, and 1.0% (n = 3) engaged in suicidal behavior after initiating treatment. To date, hospital records show no suicide deaths since 2016 among clinic patients who received CPT. Suicide risk level was not associated with CPT tolerability, and PTSD symptom change was equivalent across groups, ps = .085-.976. Veterans across groups reported clinically significant reductions in PTSD symptoms. The tested suicide risk categorization schemes performed similarly in differentiating the odds of CPT completion and PTSD symptom reduction. These results suggest that veterans with PTSD and an increased risk of suicide, including those with previous suicide attempts and current ideation, can tolerate and benefit from CPT. Additional variables must be considered to truly determine the acute and imminent suicide risk that would deem CPT to be contraindicated.

The construct validity of the multidimensional AIMES connection to nature scale: Measuring human relationships with nature.

Over the last decades, a plethora of nature connectedness measures have been developed, including unidimensional scales and others claiming to be multidimensional scales. Recently, Ives et al. (2018) conceptualised connection with nature as five general categories including attachment, cognition/identity, materialistic consumption, experiential components, and spiritual connection to nature. The current research presents a theory-driven approach to scale construction capturing the five factors similar to those described by Ives et al. (2018); the AIMES scale. The scale was developed in cooperation with practitioners and academics working in the field of human-nature interactions and its construct validity was tested with a representative sample of 3090 Victorians. Confirmatory factor analysis reinforced the five-factor model, showing that all factors correlated but were statistically distinct from one another. The second-order factor model also provided support for connection with nature as an overarching variable that can find expression to various degrees in the five primary factors. Finally, we found associations between the AIMES-factors and conceptually related measures of environmental values, environmental behaviours, environmental awareness, and time spent in nature. A short version of the scale is also presented for use in evaluation where brevity is required without compromising reliability and validity.

Vitamin C to Pregnant Smokers Persistently Improves Infant Airway Function to 12†Months of Age: A Randomised Trial.

BACKGROUND: Vitamin C (500 mg·day-1) supplementation for pregnant smokers has been reported to increase newborn pulmonary function and infant forced expiratory flows (FEFs) at 3 months of age. Its effect on airway function through 12 months of age has not been reported. OBJECTIVE: To assess whether vitamin C supplementation to pregnant smokers is associated with a sustained increased airway function in their infants through 12 months of age. METHODS: This is a prespecified secondary outcome of a randomised, double-blind, placebo-controlled trial that randomised 251 pregnant smokers between 13 and 23 weeks of gestation: 125 to 500 mg·day-1 vitamin C and 126 to placebo. Smoking cessation counselling was provided. FEFs performed at 3 and 12 months of age were analysed by repeated measures analysis of covariance. RESULTS: FEFs were performed in 222 infants at 3 months and 202 infants at 12 months of age. The infants allocated to vitamin C had significantly increased FEFs over the first year of life compared to those allocated to placebo. The overall increased flows were: 40.2 mL·sec-1 for FEF75 (adjusted 95% CI for difference 6.6 to 73.8; p=0.025); 58.3 mL·sec-1 for FEF50 (95% CI 10.9 to 105.8; p=0.0081); and 55.1 mL·sec-1 for FEF25-75 (95% CI, 9.7 to 100.5; p=0.013). CONCLUSIONS: In offspring of pregnant smokers randomised to vitamin C versus placebo, vitamin C during pregnancy was associated with a small but significantly increased airway function at 3 and 12 months of age, suggesting a potential shift to a higher airway function trajectory curve. Continued follow-up is underway.

Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE).

BACKGROUND: Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. METHODS: Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3-14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). RESULTS: Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. CONCLUSIONS: Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action.

Energy-efficient information transfer at thalamocortical synapses.

We have previously shown that the physiological size of postsynaptic currents maximises energy efficiency rather than information transfer across the retinothalamic relay synapse. Here, we investigate information transmission and postsynaptic energy use at the next synapse along the visual pathway: from relay neurons in the thalamus to spiny stellate cells in layer 4 of the primary visual cortex (L4SS). Using both multicompartment Hodgkin-Huxley-type simulations and electrophysiological recordings in rodent brain slices, we find that increasing or decreasing the postsynaptic conductance of the set of thalamocortical inputs to one L4SS cell decreases the energy efficiency of information transmission from a single thalamocortical input. This result is obtained in the presence of random background input to the L4SS cell from excitatory and inhibitory corticocortical connections, which were simulated (both excitatory and inhibitory) or injected experimentally using dynamic-clamp (excitatory only). Thus, energy efficiency is not a unique property of strong relay synapses: even at the relatively weak thalamocortical synapse, each of which contributes minimally to the output firing of the L4SS cell, evolutionarily-selected postsynaptic properties appear to maximise the information transmitted per energy used.

Oral Vitamin C (500 mg/d) to Pregnant Smokers Improves Infant Airway Function at 3 Months (VCSIP). A Randomized Trial.

Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests. Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the α5 nicotinic acetylcholine receptor. Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo. Measurements and Main Results: The primary outcome was FEF75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF50 and FEF25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, -3.33 to 35.64; P = 0.10), FEF50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the α5 nicotinic acetylcholine receptor (rs16969968). Conclusions: Although the primary outcome of FEF75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF50 and FEF25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF50 and FEF25-75) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT01723696).

Nonlinear change processes and the emergence of suicidal behavior: a conceptual model based on the fluid vulnerability theory of suicide.

Although ideation-to-action theories of suicide aim to explain the emergence of suicidal behaviors, researchers have primarily focused on the content of underlying mechanisms (i.e., who dies by suicide). Much less attention has focused on the temporal dynamics of suicide risk (i.e., when suicide occurs). The fluid vulnerability theory conceptualizes suicide as an inherently dynamic construct that follows a nonlinear time course. Newer research implicates the existence of multiple nonlinear change processes among suicidal individuals, some of which appear to be associated with the emergence of suicidal behavior. The cusp catastrophe model provides a useful model for conceptualizing these change processes and provides a foundation for explaining a number of poorly understood phenomena including sudden emergence of suicidal behavior without prior suicidal planning. The implications of temporal dynamics for suicide-focused theory, practice, and research are discussed.

Scurvy presenting with limp and weakness: a case report.

BACKGROUND: Scurvy is one of the oldest diseases known to mankind. Although presently rare in the developed world, scurvy was a common potentially fatal disease. In recent times, the most common risk factors for scurvy include alcoholism, low socioeconomic status, and severely poor nutrition or dietary restriction secondary to psychiatric illness or developmental disorders. Our case demonstrates the importance of having a high index of clinical suspicion of an uncommon disease in developed countries and emphasizes the necessity of a dietary screening that could potentially reduce extensive work-up in patients with nonspecific complaints. CASE PRESENTATION: We report a case of a 3-year-old previously healthy female originally seen in the rheumatology clinic for limp. She developed weakness and was admitted to the hospital for further evaluation. She underwent extensive diagnostic testing including blood work, magnetic resonance imaging, lumbar puncture, electromyogram, and nerve conduction studies. Ultimately, her vitamin C level returned undetectable. She had immediate and complete improvement upon starting vitamin C supplementation. CONCLUSIONS: Despite being developmentally appropriate, our patient's refusal to eat fruits or vegetables had limited her diet, emphasizing the importance of obtaining a diet history in a child presenting with an unknown diagnosis. In addition, our patient had no other characteristic features of scurvy, which further supports the need to consider this diagnosis in a child presenting with lower extremity weakness or abnormal gait.

Positive and detached reappraisal in older adulthood: A temporal examination of gaze patterns.

Objectives: Cognitive reappraisal is an emotion regulation strategy that involves the adaptive restructuring of one's thoughts surrounding an emotionally evocative stimulus. Previous studies have produced mixed results on how distinct reappraisal and attentional processes are, but few studies have teased apart specific reappraisal methods. This is of particular interest in aging as older adults' regulation success may vary by reappraisal type. The current study examined whether detached and positive reappraisal are associated with distinct temporal patterns of attention in a sample of older adults. Method: 29 older adult participants viewed negative IAPS images and were instructed to implement both positive and detached reappraisal while eye movements were monitored. Participants also reported on their mood before and after viewing the images. Results: Participants fixated on negative areas early on and looked at them less over time, however their attention was oriented specifically towards the most negative region during reappraisal. They also re-fixated on the negative areas of the images during the last second of viewing during detached reappraisal, and reported feeling best while using this strategy. Conclusion: These findings provide information about the temporal nature of visual attention while utilizing distinct cognitive reappraisal strategies. Results highlight the importance of further teasing apart differences between detached and positive reappraisal as regulatory success and attentional shifts differ between these reappraisal types in older adulthood.

Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension.

BACKGROUND: Data on the effect of initial combination therapy with ambrisentan and tadalafil on long-term outcomes in patients with pulmonary arterial hypertension are scarce. METHODS: In this event-driven, double-blind study, we randomly assigned, in a 2:1:1 ratio, participants with World Health Organization functional class II or III symptoms of pulmonary arterial hypertension who had not previously received treatment to receive initial combination therapy with 10 mg of ambrisentan plus 40 mg of tadalafil (combination-therapy group), 10 mg of ambrisentan plus placebo (ambrisentan-monotherapy group), or 40 mg of tadalafil plus placebo (tadalafil-monotherapy group), all administered once daily. The primary end point in a time-to-event analysis was the first event of clinical failure, which was defined as the first occurrence of a composite of death, hospitalization for worsening pulmonary arterial hypertension, disease progression, or unsatisfactory long-term clinical response. RESULTS: The primary analysis included 500 participants; 253 were assigned to the combination-therapy group, 126 to the ambrisentan-monotherapy group, and 121 to the tadalafil-monotherapy group. A primary end-point event occurred in 18%, 34%, and 28% of the participants in these groups, respectively, and in 31% of the pooled-monotherapy group (the two monotherapy groups combined). The hazard ratio for the primary end point in the combination-therapy group versus the pooled-monotherapy group was 0.50 (95% confidence interval [CI], 0.35 to 0.72; P<0.001). At week 24, the combination-therapy group had greater reductions from baseline in N-terminal pro-brain natriuretic peptide levels than did the pooled-monotherapy group (mean change, -67.2% vs. -50.4%; P<0.001), as well as a higher percentage of patients with a satisfactory clinical response (39% vs. 29%; odds ratio, 1.56 [95% CI, 1.05 to 2.32]; P=0.03) and a greater improvement in the 6-minute walk distance (median change from baseline, 48.98 m vs. 23.80 m; P<0.001). The adverse events that occurred more frequently in the combination-therapy group than in either monotherapy group included peripheral edema, headache, nasal congestion, and anemia. CONCLUSIONS: Among participants with pulmonary arterial hypertension who had not received previous treatment, initial combination therapy with ambrisentan and tadalafil resulted in a significantly lower risk of clinical-failure events than the risk with ambrisentan or tadalafil monotherapy. (Funded by Gilead Sciences and GlaxoSmithKline; AMBITION ClinicalTrials.gov number, NCT01178073.).