Mechanisms of change in posttraumatic headache-related disability: A mediation model.

OBJECTIVE: To explore whether the association between change in headache management self-efficacy and posttraumatic headache-related disability is partially mediated by a change in anxiety symptom severity. BACKGROUND: Many cognitive-behavioral therapy treatments for headache emphasize stress management, which includes anxiety management strategies; however, little is currently known about mechanisms of change in posttraumatic headache-related disability. Increasing our understanding of mechanisms could lead to improvements in treatments for these debilitating headaches. METHODS: This study is a secondary analysis of veterans (N = 193) recruited to participate in a randomized clinical trial of cognitive-behavioral therapy, cognitive processing therapy, or treatment as usual for persistent posttraumatic headache. The direct relationship between headache management self-efficacy and headache-related disability, along with partial mediation through change in anxiety symptoms was tested. RESULTS: The mediated latent change direct, mediated, and total pathways were statistically significant. The path analysis supported a significant direct pathway between headache management self-efficacy and headache-related disability (b = -0.45, p < 0.001; 95% confidence interval [CI: -0.58, -0.33]). The total effect of change of headache management self-efficacy scores on change in Headache Impact Test-6 scores was significant with a moderate-to-strong effect (b = -0.57, p = 0.001; 95% CI [-0.73, -0.41]). There was also an indirect effect through anxiety symptom severity change (b = -0.12, p = 0.003; 95% CI [-0.20, -0.04]). CONCLUSIONS: In this study, most of the improvements in headache-related disability were related to increased headache management self-efficacy with mediation occurring through change in anxiety. This indicates that headache management self-efficacy is a likely mechanism of change of posttraumatic headache-related disability with decreases in anxiety explaining part of the improvement in headache-related disability.

First North American fossil monkey and early Miocene tropical biotic interchange.

New World monkeys (platyrrhines) are a diverse part of modern tropical ecosystems in North and South America, yet their early evolutionary history in the tropics is largely unknown. Molecular divergence estimates suggest that primates arrived in tropical Central America, the southern-most extent of the North American landmass, with several dispersals from South America starting with the emergence of the Isthmus of Panama 3-4 million years ago (Ma). The complete absence of primate fossils from Central America has, however, limited our understanding of their history in the New World. Here we present the first description of a fossil monkey recovered from the North American landmass, the oldest known crown platyrrhine, from a precisely dated 20.9-Ma layer in the Las Cascadas Formation in the Panama Canal Basin, Panama. This discovery suggests that family-level diversification of extant New World monkeys occurred in the tropics, with new divergence estimates for Cebidae between 22 and 25 Ma, and provides the oldest fossil evidence for mammalian interchange between South and North America. The timing is consistent with recent tectonic reconstructions of a relatively narrow Central American Seaway in the early Miocene epoch, coincident with over-water dispersals inferred for many other groups of animals and plants. Discovery of an early Miocene primate in Panama provides evidence for a circum-Caribbean tropical distribution of New World monkeys by this time, with ocean barriers not wholly restricting their northward movements, requiring a complex set of ecological factors to explain their absence in well-sampled similarly aged localities at higher latitudes of North America.

Persistent posttraumatic headaches and functioning in veterans: Injury type can matter.

OBJECTIVE: To characterize the relationship between head trauma types (blast injury, blunt injury, combined blast+blunt injury) with subsequent headache presentations and functioning. BACKGROUND: Posttraumatic headaches (PTHs), the most common sequelae of traumatic brain injury (TBI), are painful and disabling. More than 400,000 veterans report having experienced a TBI, and understanding the predictors of PTHs may guide treatment developments. METHODS: This study used a nested-cohort design analyzing baseline data from a randomized clinical trial of cognitive behavioral therapy for PTH (N = 190). Participants had PTH (from blast and/or blunt head trauma) and symptoms of posttraumatic stress disorder (PTSD). The Structured Diagnostic Interview for Headache-Revised and Ohio State University Traumatic Brain Injury Identification Method were used to phenotype headaches and head injury histories, respectively. RESULTS: Individuals with persistent PTHs after a combined blast and blunt head trauma were more likely (OR =3.45; 95% CI [1.41, 8.4]) to experience chronic (vs. episodic) PTHs compared with the blunt trauma only group (23/33, 70% vs. 26/65, 40%, respectively); and they were more likely (OR =2.51; 95% CI [1.07, 5.9]) to experience chronic PTH compared with the blast trauma only group (44/92, 48%). There were no differences between head injury type on headache-related disability, depression symptoms, or severity of PTSD symptoms. CONCLUSION: The combination of blast and blunt injuries was associated with headache chronicity, but not headache disability. Considering the refractory nature of chronic headaches, the potential added and synergistic effects of distinct head injuries warrant further study.

Evaluation of Helicobacter pylori Infection and Clarithromycin Resistance in Strains From Symptomatic Colombian Children.

The aim of the study was to determine the current prevalence of Helicobacter pylori in symptomatic Colombian children and evaluate the presence of mutations associated with clarithromycin resistance. Biopsies from 133 children were analyzed. The gastric fragment was used for urease test and reused for polymerase chain reaction sequencing of the 23SrDNA gene. Mutations were detected by bioinformatic analysis. Polymerase chain reaction sequencing established that H pylori infection was present in 47% of patients. Bioinformatics analysis of the 62 positive sequences for 23SrDNA revealed that 92% exhibited a genotype susceptible to clarithromycin, whereas the remaining strains (8%) showed mutations associated with clarithromycin resistance. The low rate of resistance to clarithromycin (8%) suggests that conventional treatment methods are an appropriate choice for children. Recycling a biopsy that is normally discarded reduces the risks associated with the procedure. The 23SrDNA gene amplification could be used for a dual purpose: detection of H pylori and determination of susceptibility to clarithromycin.

Traumatic Brain Injury Severity, Comorbidity, Social Support, Family Functioning, and Community Reintegration Among Veterans of the Afghanistan and Iraq Wars.

OBJECTIVE: To examine the association between traumatic brain injury (TBI) severity; social, family, and community reintegration outcomes; and return to work status among post-9/11 veterans in Department of Veterans Affairs (VA) care. DESIGN: Retrospective observational cohort study. SETTING: Mail/online survey fielded to a national sample of veterans. PARTICIPANTS: Sample of post-9/11 veterans with at least 3 years of VA care stratified according to TBI severity and comorbidities who completed and returned surveys (N=2023). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Deployment Risk and Resilience Inventory-2 family functioning and social support subscales; Military to Civilian Questionnaire; and employment status. RESULTS: Bivariate analyses revealed that veterans with every classification of TBI severity reported significantly more difficulty on social, family, and community reintegration outcomes than those with no TBI. In the fully adjusted model, veterans with unclassified and moderate/severe TBI reported significantly more difficulty with community reintegration and were less likely to be employed relative to those with no TBI; those with unclassified TBI also reported significantly more difficulty with family functioning. Veterans with mild TBI also reported significantly more difficulty with community reintegration. CONCLUSIONS: This study provides insight into long-term outcomes associated with TBI in post-9/11 veterans and suggests that exposure to TBI has a negative effect on social and family functioning, community reintegration, and return to work even after controlling for comorbidity, deployment experiences, and sociodemographic characteristics. Additional research is required to explicate what appears to be complex interactions among TBI severity, psychosocial well-being, combat exposures, and socioeconomic resources in this population.

Long-term physical and mental health outcomes associated with traumatic brain injury severity in post-9/11 veterans: A retrospective cohort study.

OBJECTIVES: To examine long-term outcomes of self-reported physical and mental health among Post-9/11 Veterans stratified by traumatic brain injury (TBI) severity, we hypothesized that more severe TBI would be associated with significantly poorer outcomes. METHODS: A prospective longitudinal survey of physical and mental health status was conducted with a national cohort of Post-9/11 Veterans. We then used generalized linear models (GLM) to assess the unique contribution of TBI severity on long-term outcomes after controlling for socio-demographic characteristics, comorbidity phenotypes, and deployment experiences. RESULTS: TBI of any severity was associated with significantly poorer outcomes relative to the No TBI group. However, the manifestation of these outcomes identified in our study differed meaningfully by TBI severity level. CONCLUSIONS: Veterans with any TBI exposure experience poorer long-term outcomes than those with no TBI even when covariates are considered. In particular, measures of somatization, PTSD symptom distress, and depression indicate pervasive and long-term health concerns among individuals with TBI. Additional research is required to fully explicate what appear to be complex relationships among TBI severity, physical and mental well-being, combat exposures, and socioeconomic resources in this population.

Structural Analysis of Variability and Interaction of the N-terminal of the Oncogenic Effector CagA of Helicobacter pylori with Phosphatidylserine.

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the phosphatidylserine and the docking of three mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA⁻Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score; mutations in this position were evaluated to observe the differences in intermolecular forces for the CagA⁻Phosphatidylserine complex. We evaluated the docking of three mutations: K636A, K636R and K636N. The crystal and mutation models presented a ΔG of -8.919907, -8.665261, -8.701923, -8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG ( χ 2 ( 1 ) = 93.82 , p-value < 2.2 × 10 - 16 ) and the H-bonds ( χ 2 ( 1 ) = 91.93 , p-value < 2.2 × 10 - 16 ). Overall, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA⁻Phosphatidylserine complex interaction.

A cohort study examining headaches among veterans of Iraq and Afghanistan wars: Associations with traumatic brain injury, PTSD, and depression.

OBJECTIVES: To describe the prevalence and persistence of headache and associated conditions in an inception cohort of U.S. veterans of Iraq and Afghanistan wars. BACKGROUND: Iraq and Afghanistan war veterans (IAV) suffer from persistent and difficult-to-treat headaches that have been found to co-occur with traumatic brain injury (TBI) and other deployment related comorbidities. METHODS: This longitudinal retrospective cohort study used data from the national Veterans Health Administration (VA) data repository for IAV who first received VA care in 2008 (baseline) and also received care each year in 2009, 2010, and 2011. We used ICD-9-CM codes, to identify those treated for headache each year (2008-2011). Individuals with headache diagnosed each year were classified as having persistent headache. We also identified comorbidities that may be associated with baseline headache using algorithms validated for use with ICD-9-CM codes. Comorbidities included TBI, posttraumatic stress disorder (PTSD), depression, and conditions associated with these diagnoses (anxiety, memory/attention/cognition, neck pain, tinnitus/hyperacusis, photosensitivity/photo blurring, insomnia, malaise/fatigue, and vertigo/dizziness). Multivariable logistic regression analysis was used to determine characteristics associated with baseline headache as well as those associated with persistent headache. RESULTS: Among all IAV, 38,426 received their first year of VA care in 2008 and had care each year 2009-2011: 13.7% of these were diagnosed with headache in 2008. Veterans diagnosed with headache in 2008 were more likely than those without a headache diagnosis to also have a diagnosis of TBI alone (adjusted odds ratios [AOR] 6.75; 95% CI 5.79-7.86), TBI + depression (AOR 7.09; 95% CI 5.23-9.66), TBI + PTSD (AOR 10.16; 95% CI 8.96-11.53), TBI + PTSD + depression (AOR 9.40; 95% CI 8.12-10.09), and neck pain (AOR 2.44; 95% CI 2.14-2.77). Among those with headache diagnosis in 2008, 24.3% had a headache diagnosis each of the subsequent years of care (persistent headache). While diagnoses of TBI, PTSD, and/or depression at baseline were not associated with headache persistence, persistence was more likely for individuals with baseline tinnitus/hyperacusis (AOR 1.21; 95% CI 1.02-1.45), insomnia (AOR 1.19; 95% CI 1.02-1.39), and vertigo/dizziness (AOR 1.83; 95% CI 1.30-2.57). CONCLUSIONS: Our results indicate that TBI alone is a strong predictor of headache in the first year of VA care among IAV and that comorbid psychiatric comorbidities increase the likelihood of headache among individuals with TBI. However, among those with baseline headache, only tinnitus, insomnia, and vertigo were baseline clinical predictors of headache persistence. These results suggest that attention to other symptoms and conditions early in the diagnosis and treatment of headaches may be important for understanding prognosis. These comorbidities offer potential targets for intervention strategies that may help address postdeployment headaches.

A retrospective cohort study of comorbidity trajectories associated with traumatic brain injury in veterans of the Iraq and Afghanistan wars.

OBJECTIVES: To identify and validate trajectories of comorbidity associated with traumatic brain injury in male and female Iraq and Afghanistan war Veterans (IAV). METHODS: Derivation and validation cohorts were compiled of IAV who entered the Department of Veterans Affairs (VA) care and received 3 years of VA care between 2002-2011. Chronic disease and comorbidities associated with deployment including TBI were identified using diagnosis codes. A latent class analysis (LCA) of longitudinal comorbidity data was used to identify trajectories of comorbidity. RESULTS: LCA revealed five trajectories that were similar for women and men: (1) Healthy, (2) Chronic Disease, (3) Mental Health, (4) Pain and (5) Polytrauma Clinical Triad (PCT: pain, mental health and TBI). Two additional classes found in men were 6) Minor Chronic and 7) PCT with chronic disease. Among these gender-stratified trajectories, it was found that women were more likely to experience headache (Pain trajectory) and depression (Mental Health trajectory), while men were more likely to experience lower back pain (Pain trajectory) and substance use disorder (Mental Health trajectory). The probability of TBI was highest in the PCT-related trajectories, with significantly lower probabilities in other trajectories. CONCLUSIONS: It was found that TBI was most common in PCT-related trajectories, indicating that TBI is commonly comorbid with pain and mental health conditions for both men and women. The relatively young age of this cohort raises important questions regarding how disease burden, including the possibility of neurodegenerative sequelae, will accrue alongside normal age-related decline in individuals with TBI. Additional 'big data' methods and a longer observation period may allow the development of predictive models to identify individuals with TBI that are at-risk for adverse outcomes.

A Late Cretaceous Piper (Piperaceae) from Colombia and diversification patterns for the genus.

PREMISE OF THE STUDY: Documented fossil floras in the neotropics are sparse, yet their records provide evidence on the spatial and temporal occurrence of taxa, allowing for testing of biogeographical and diversification scenarios on individual lineages. A new fossil Piper from the Late Cretaceous of Colombia is described here, and its importance for assessing diversification patterns in the genus is addressed. METHODS: Leaf architecture of 32 fossil leaf compressions from the Guaduas Formation was compared with that of 294 extant angiosperm species. The phylogenetic position of the fossil named Piper margaritae sp. nov. was established based on leaf traits and a molecular scaffold of Piper. The age of the fossil was independently used as a calibration point for divergence time estimations. KEY RESULTS: Natural affinities of P. margaritae to the Schilleria clade of Piper indicate that the genus occurred in tropical America by the Late Cretaceous. Estimates of age divergence and lineage accumulation reveal that most of the extant diversity of the genus accrued during the last ∼30 Myr. CONCLUSIONS: The recent radiation of Piper is coeval with both the Andean uplift and the emergence of Central America, which have been proposed as important drivers of diversity. This pattern could exemplify a recurrent theme among many neotropical plant lineages.

Giant boid snake from the Palaeocene neotropics reveals hotter past equatorial temperatures.

The largest extant snakes live in the tropics of South America and southeast Asia where high temperatures facilitate the evolution of large body sizes among air-breathing animals whose body temperatures are dependant on ambient environmental temperatures (poikilothermy). Very little is known about ancient tropical terrestrial ecosystems, limiting our understanding of the evolution of giant snakes and their relationship to climate in the past. Here we describe a boid snake from the oldest known neotropical rainforest fauna from the Cerrejón Formation (58-60 Myr ago) in northeastern Colombia. We estimate a body length of 13 m and a mass of 1,135 kg, making it the largest known snake. The maximum size of poikilothermic animals at a given temperature is limited by metabolic rate, and a snake of this size would require a minimum mean annual temperature of 30-34 degrees C to survive. This estimate is consistent with hypotheses of hot Palaeocene neotropics with high concentrations of atmospheric CO(2) based on climate models. Comparison of palaeotemperature estimates from the equator to those from South American mid-latitudes indicates a relatively steep temperature gradient during the early Palaeogene greenhouse, similar to that of today. Depositional environments and faunal composition of the Cerrejón Formation indicate an anaconda-like ecology for the giant snake, and an earliest Cenozoic origin of neotropical vertebrate faunas.

The prevalence of epilepsy and association with traumatic brain injury in veterans of the Afghanistan and Iraq wars.

OBJECTIVE: To examine the association of epilepsy with traumatic brain injury (TBI) in Afghanistan and Iraq (Operation Enduring Freedom [OEF]/Operation Iraqi Freedom [OIF]) Veterans. DESIGN: Cross-sectional observational study. PARTICIPANTS: A total 256 284 OEF/OIF Veterans who received inpatient and outpatient care in the Veterans Health Administration in fiscal years 2009-2010. MAIN OUTCOME MEASURES: We used algorithms developed for use with International Classification of Diseases, Ninth Revision, Clinical Modification, codes to identify epilepsy, TBI (penetrating TBI [pTBI]/other TBI), and other risk factors for epilepsy (eg, stroke). TBI and other risk factors were identified prior to the index date (first date of seizure or October 1, 2009) for primary analyses. RESULTS: Epilepsy prevalence was 10.6 per 1000 (N = 2719) in fiscal year 2010; age-adjusted prevalence was 6.1. Of 37 718 individuals with a diagnosis of TBI, 29 297 Veterans had a diagnosis of TBI prior to the index date. Statistically significant associations were found between epilepsy and prior TBI diagnosis (pTBI: adjusted odds ratio = 18.77 [95% confidence interval, 9.21-38.23]; other TBI: adjusted odds ratio = 1.64 [1.43-1.89]). CONCLUSIONS: Among OEF/OIF Veterans, epilepsy was associated with previous TBI diagnosis, with pTBI having the strongest association. Because war-related epilepsy in Vietnam War Veterans with TBI continued 35 years postwar, a detailed, prospective study is needed to understand the relationship between epilepsy and TBI severity in OEF/OIF Veterans.

VA Vascular Injury Study (VAVIS): VA-DoD extremity injury outcomes collaboration.

BACKGROUND: Limb injuries comprise 50-60% of U.S. Service member's casualties of wars in Afghanistan and Iraq. Combat-related vascular injuries are present in 12% of this cohort, a rate 5 times higher than in prior wars. Improvements in medical and surgical trauma care, including initial in-theatre limb salvage approaches (IILS) have resulted in improved survival and fewer amputations, however, the long-term outcomes such as morbidity, functional decline, and risk for late amputation of salvaged limbs using current process of care have not been studied. The long-term care of these injured warfighters poses a significant challenge to the Department of Defense (DoD) and Department of Veterans Affairs (VA). METHODS/DESIGN: The VA Vascular Injury Study (VAVIS): VA-DoD Extremity Injury Outcomes Collaborative, funded by the VA, Health Services Research and Development Service, is a longitudinal cohort study of Veterans with vascular extremity injuries. Enrollment will begin April, 2015 and continue for 3 years. Individuals with a validated extremity vascular injury in the Department of Defense Trauma Registry will be contacted and will complete a set of validated demographic, social, behavioral, and functional status measures during interview and online/ mailed survey. Primary outcome measures will: 1) Compare injury, demographic and geospatial characteristics of patients with IILS and identify late vascular surgery related limb complications and health care utilization in Veterans receiving VA vs. non-VA care, 2) Characterize the preventive services received by individuals with vascular repair and related outcomes, and 3) Describe patient-reported functional outcomes in Veterans with traumatic vascular limb injuries. DISCUSSION: This study will provide key information about the current process of care for Active Duty Service members and Veterans with polytrauma/vascular injuries at risk for persistent morbidity and late amputation. The results of this study will be the first step for clinicians in VA and military settings to generate evidence-based treatment and care approaches to these injuries. It will identify areas where rehabilitation medicine and vascular specialty care or telehealth options are needed to allow for better planning, resource utilization, and improved DoD-to-VA care transitions.

Traumatic brain injury in veterans of the wars in Iraq and Afghanistan: communication disorders stratified by severity of brain injury.

OBJECTIVE: To describe the prevalence of communication disorders in veterans of the wars in Iraq and Afghanistan with traumatic brain injury (TBI). DESIGN: Retrospective study of the prevalence of aphasia, fluency and voice disorders among veterans with different severity levels of TBI. Data was obtained from the VA National repository for OEF/OIF/OND veterans who received VA care in Fiscal Years 2010 and 2011. RESULTS: Among the 303,716 veterans in this study, 1848 were diagnosed with a communication disorder; 40% of these were also diagnosed with a TBI. Voice disorders were the most prevalent diagnosis (3.5 per 1000) followed by aphasia (1.9 per 1000) and fluency disorder (0.7 per 1000). Individuals with a TBI diagnosis were more likely to have a diagnosis of aphasia, followed by fluency and then voice disorder. The odds ratio (OR) of aphasia with TBI was 11.09-252.75 (95% CI = 8.78-441.52, p < 0.01). OR for fluency disorders with TBI was 3.58-10.41 (95% CI = 2.56-42.40, p < 0.01) and association of voice disorders with TBI was significant for all levels of TBI severity (OR = 1.5-6.61, 95% CI = 1.24-14.05, p < 0.01). CONCLUSIONS: Veterans who sustained a TBI were more likely to have a diagnosis of a communication disorder, regardless of TBI severity. Those with TBI, including mild TBI, should be screened and evaluated for communication disorders.

Palynological composition of a Lower Cretaceous South American tropical sequence: climatic implications and diversity comparisons with other latitudes.

PREMISE OF THE STUDY: Reconstruction of floristic patterns during the early diversification of angiosperms is impeded by the scarce fossil record, especially in tropical latitudes. Here we collected quantitative palynological data from a stratigraphic sequence in tropical South America to provide floristic and climatic insights into such tropical environments during the Early Cretaceous. METHODS: We reconstructed the floristic composition of an Aptian-Albian tropical sequence from central Colombia using quantitative palynology (rarefied species richness and abundance) and used it to infer its predominant climatic conditions. Additionally, we compared our results with available quantitative data from three other sequences encompassing 70 floristic assemblages to determine latitudinal diversity patterns. KEY RESULTS: Abundance of humidity indicators was higher than that of aridity indicators (61% vs. 10%). Additionally, we found an angiosperm latitudinal diversity gradient (LDG) for the Aptian, but not for the Albian, and an inverted LDG of the overall diversity for the Albian. Angiosperm species turnover during the Albian, however, was higher in humid tropics. CONCLUSIONS: There were humid climates in northwestern South America during the Aptian-Albian interval contrary to the widespread aridity expected for the tropical belt. The Albian inverted overall LDG is produced by a faster increase in per-sample angiosperm and pteridophyte diversity in temperate latitudes. However, humid tropical sequences had higher rates of floristic turnover suggesting a higher degree of morphological variation than in temperate regions.

Late Paleocene fossils from the Cerrejon Formation, Colombia, are the earliest record of Neotropical rainforest.

Neotropical rainforests have a very poor fossil record, making hypotheses concerning their origins difficult to evaluate. Nevertheless, some of their most important characteristics can be preserved in the fossil record: high plant diversity, dominance by a distinctive combination of angiosperm families, a preponderance of plant species with large, smooth-margined leaves, and evidence for a high diversity of herbivorous insects. Here, we report on an approximately 58-my-old flora from the Cerrejón Formation of Colombia (paleolatitude approximately 5 degrees N) that is the earliest megafossil record of Neotropical rainforest. The flora has abundant, diverse palms and legumes and similar family composition to extant Neotropical rainforest. Three-quarters of the leaf types are large and entire-margined, indicating rainfall >2,500 mm/year and mean annual temperature >25 degrees C. Despite modern family composition and tropical paleoclimate, the diversity of fossil pollen and leaf samples is 60-80% that of comparable samples from extant and Quaternary Neotropical rainforest from similar climates. Insect feeding damage on Cerrejón fossil leaves, representing primary consumers, is abundant, but also of low diversity, and overwhelmingly made by generalist feeders rather than specialized herbivores. Cerrejón megafossils provide strong evidence that the same Neotropical rainforest families have characterized the biome since the Paleocene, maintaining their importance through climatic phases warmer and cooler than present. The low diversity of both plants and herbivorous insects in this Paleocene Neotropical rainforest may reflect an early stage in the diversification of the lineages that inhabit this biome, and/or a long recovery period from the terminal Cretaceous extinction.

Complex pain phenotypes: Suicidal ideation and attempt through latent multimorbidity.

BACKGROUND: Given the relatively high rates of suicidal ideation and attempt among people with chronic pain, there is a need to understand the underlying factors to target suicide prevention efforts. To date, no study has examined the association between pain phenotypes and suicide related behaviors among those with mild traumatic brain injuries. OBJECTIVE: To determine if pain phenotypes were independently associated with suicidal ideation / attempt or if comorbidities within the pain phenotypes account for the association between pain phenotypes and suicide related behaviors. METHODS: This is a longitudinal retrospective cohort study of suicide ideation/attempts among pain phenotypes previously derived using general mixture latent variable models of the joint distribution of repeated measures of pain scores and pain medications/treatment. We used national VA inpatient, outpatient, and pharmacy data files for Post-9/11 Veterans with mild traumatic injury who entered VA care between fiscal years (FY) 2007 and 2009. We considered a counterfactual causal modeling framework to assess the extent that the pain phenotypes during years 1-5 of VA care were predictive of suicide ideation/attempt during years 6-8 of VA care conditioned on covariates being balanced between pain phenotypes. RESULTS: Without adjustment, pain phenotypes were significant predictors of suicide related behaviors. When we used propensity scores to balance the comorbidities present in the pain phenotypes, the pain phenotypes were no longer significantly associated with suicide related behaviors. CONCLUSION: These findings suggest that suicide ideation/attempt is associated with pain trajectories primarily through latent multimorbidity. Therefore, it is critical to identify and manage comorbidities (e.g., depression, post-traumatic stress disorder) to prevent tragic outcomes associated with suicide related behaviors throughout the course of chronic pain and mild traumatic brain injury management.

PTSD symptoms and tinnitus severity: An analysis of veterans with posttraumatic headaches.

OBJECTIVE: Tinnitus and posttraumatic stress disorder (PTSD) are among the top service-connected disabilities within the Veterans Health Administration. Extant research shows that there is considerable overlap between tinnitus-related distress and PTSD, including sleep difficulty, irritability, hyperarousal, and concentration problems. However, no studies have prospectively examined the relationship between the two disorders. The purpose of this study was to examine that relationship. METHOD: Participants (N = 112) with posttraumatic headache completed measures of tinnitus and PTSD. Correlational analyses and analyses of variance were conducted to examine the associations with PTSD symptom clusters and factors of tinnitus-related distress. RESULTS: Approximately, half of participants with tinnitus demonstrated severe impairment. Correlational analyses indicated that reexperiencing, avoidance, negative emotions and cognitions, and hyperarousal PTSD symptoms were significantly related to many factors of tinnitus-related distress, including intrusiveness of tinnitus, perceived loudness, awareness, and annoyance. Participants with severe tinnitus demonstrated significantly greater reexperiencing, negative mood/cognitions, hyperarousal, and PTSD total severity compared to those with mild or moderate tinnitus. CONCLUSIONS: Trauma therapists should assess for the presence of tinnitus in order to more fully conceptualize key health problems of help-seeking patients. Heightened psychological symptoms seemingly related to PTSD may be a function of tinnitus-related distress. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cognitive Behavioral Therapy for Veterans With Comorbid Posttraumatic Headache and Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial.

Importance: Posttraumatic headache is the most disabling complication of mild traumatic brain injury. Posttraumatic stress disorder (PTSD) symptoms are often comorbid with posttraumatic headache, and there are no established treatments for this comorbidity. Objective: To compare cognitive behavioral therapies (CBTs) for headache and PTSD with treatment per usual (TPU) for posttraumatic headache attributable to mild traumatic brain injury. Design, Setting, and Participants: This was a single-site, 3-parallel group, randomized clinical trial with outcomes at posttreatment, 3-month follow-up, and 6-month follow-up. Participants were enrolled from May 1, 2015, through May 30, 2019; data collection ended on October 10, 2019. Post-9/11 US combat veterans from multiple trauma centers were included in the study. Veterans had comorbid posttraumatic headache and PTSD symptoms. Data were analyzed from January 20, 2020, to February 2, 2022. Interventions: Patients were randomly assigned to 8 sessions of CBT for headache, 12 sessions of cognitive processing therapy for PTSD, or treatment per usual for headache. Main Outcomes and Measures: Co-primary outcomes were headache-related disability on the 6-Item Headache Impact Test (HIT-6) and PTSD symptom severity on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5) assessed from treatment completion to 6 months posttreatment. Results: A total of 193 post-9/11 combat veterans (mean [SD] age, 39.7 [8.4] years; 167 male veterans [87%]) were included in the study and reported severe baseline headache-related disability (mean [SD] HIT-6 score, 65.8 [5.6] points) and severe PTSD symptoms (mean [SD] PCL-5 score, 48.4 [14.2] points). For the HIT-6, compared with usual care, patients receiving CBT for headache reported -3.4 (95% CI, -5.4 to -1.4; P < .01) points lower, and patients receiving cognitive processing therapy reported -1.4 (95% CI, -3.7 to 0.8; P = .21) points lower across aggregated posttreatment measurements. For the PCL-5, compared with usual care, patients receiving CBT for headache reported -6.5 (95% CI, -12.7 to -0.3; P = .04) points lower, and patients receiving cognitive processing therapy reported -8.9 (95% CI, -15.9 to -1.9; P = .01) points lower across aggregated posttreatment measurements. Adverse events were minimal and similar across treatment groups. Conclusions and Relevance: This randomized clinical trial demonstrated that CBT for headache was efficacious for disability associated with posttraumatic headache in veterans and provided clinically significant improvement in PTSD symptom severity. Cognitive processing therapy was efficacious for PTSD symptoms but not for headache disability. Trial Registration: ClinicalTrials.gov Identifier: NCT02419131.

Sensitivity of leaf size and shape to climate: global patterns and paleoclimatic applications.

• Paleobotanists have long used models based on leaf size and shape to reconstruct paleoclimate. However, most models incorporate a single variable or use traits that are not physiologically or functionally linked to climate, limiting their predictive power. Further, they often underestimate paleotemperature relative to other proxies. • Here we quantify leaf-climate correlations from 92 globally distributed, climatically diverse sites, and explore potential confounding factors. Multiple linear regression models for mean annual temperature (MAT) and mean annual precipitation (MAP) are developed and applied to nine well-studied fossil floras. • We find that leaves in cold climates typically have larger, more numerous teeth, and are more highly dissected. Leaf habit (deciduous vs evergreen), local water availability, and phylogenetic history all affect these relationships. Leaves in wet climates are larger and have fewer, smaller teeth. Our multivariate MAT and MAP models offer moderate improvements in precision over univariate approaches (± 4.0 vs 4.8°C for MAT) and strong improvements in accuracy. For example, our provisional MAT estimates for most North American fossil floras are considerably warmer and in better agreement with independent paleoclimate evidence. • Our study demonstrates that the inclusion of additional leaf traits that are functionally linked to climate improves paleoclimate reconstructions. This work also illustrates the need for better understanding of the impact of phylogeny and leaf habit on leaf-climate relationships.