Telehealth-Based Contingency Management Targeting Stimulant Abstinence: A Case Series From the COVID-19 Pandemic.

OBJECTIVE: Contingency management (CM) is the gold standard treatment for stimulant use disorder but typically requires twice- to thrice-weekly in-person treatment visits to objectively verify abstinence and deliver therapeutic incentives. There has been growing interest in telehealth-based delivery of CM to support broad access to this essential intervention--a need that has been emphatically underscored by the COVID-19 pandemic. Herein, we present observations from initial efforts to develop and test a protocol for telehealth-based delivery of prize-based CM treatment incentivizing stimulant abstinence. METHOD: Four participants engaged in hybrid courses of CM, including one or more telehealth-based treatment sessions, involving self-administered oral fluid testing to confirm abstinence. Observations from initial participants informed iterative improvements to telehealth procedures, and a 12-week course of telehealth-based CM was subsequently offered to two additional participants to further evaluate preliminary feasibility and acceptability. RESULTS: In most cases, participants were able to successfully join telehealth treatment sessions, self-administer oral fluid testing, and share oral fluid test results to verify stimulant abstinence. However, further improvements in telehealth-based toxicology testing may be necessary to interpret test results accurately and reliably, especially when colorimetric immunoassay results reflect substance concentrations near the cutoff for point-of-care testing devices. CONCLUSIONS: Preliminary findings suggest that telehealth-based CM is sufficiently feasible and acceptable to support future development, in particular through improved methods for remote interpretation and verification of test results. This is especially important in CM, wherein accurate and reliable detection of both early and sustained abstinence is crucial for appropriate delivery of therapeutic incentives.

Patients with cocaine use disorder exhibit reductions in delay discounting with episodic future thinking cues regardless of incarceration history.

Research examining episodic future thinking (EFT; i.e., imagining oneself in future contexts) in community samples has demonstrated reduced discounting of delayed rewards when personalized event cues are included to prompt EFT related to reward latencies. While this EFT effect was recently demonstrated in individuals with substance use disorders, it is not yet known if it manifests similarly in individuals with and without a significant incarceration history-the latter being at elevated risk for negative outcomes including criminal recidivism. Individuals with cocaine use disorder (n = 35) identified personally-relevant future events and participated in a computerized delay discounting task, involving decisions between smaller immediate rewards or larger delayed rewards with and without EFT cues. Individuals with (n = 19) and without (n = 16) a significant history of incarceration were identified using the Addiction Severity Index-Lite. A significant reduction in discounting rates was observed when event cues were included to promote EFT (p = 0.02); however, there was no main effect of incarceration history on discounting behavior, or interaction between episodic future thinking condition and incarceration history. Results suggest personalized cues included to evoke EFT reduce discounting behavior in individuals with cocaine use disorder, regardless of incarceration history. EFT-based interventions may therefore have promise to reduce impulsive decision-making in individuals with cocaine use disorder with and without a significant history of incarceration, potentially supporting improved outcomes with respect to both substance use and future criminality.

Ruminative reflection is associated with anticorrelations between the orbitofrontal cortex and the default mode network in depression: implications for repetitive transcranial magnetic stimulation.

Patients with depression who ruminate repeatedly focus on depressive thoughts; however, there are two cognitive subtypes of rumination, reflection and brooding, each associated with different prognoses. Reflection involves problem-solving and is associated with positive outcomes, whereas brooding involves passive, negative, comparison with other people and is associated with poor outcomes. Rumination has also been related to atypical functional hyperconnectivity between the default mode network and subgenual prefrontal cortex. Repetitive pulse transcranial magnetic stimulation of the prefrontal cortex has been shown to alter functional connectivity, suggesting that the abnormal connectivity associated with rumination could potentially be altered. This study examined potential repetitive pulse transcranial magnetic stimulation prefrontal cortical targets that could modulate one or both of these rumination subtypes. Forty-three patients who took part in a trial of repetitive pulse transcranial magnetic stimulation completed the Rumination Response Scale questionnaire and resting-state functional magnetic resonance imaging. Seed to voxel functional connectivity analyses identified an anticorrelation between the left lateral orbitofrontal cortex (-44, 26, -8; k = 172) with the default mode network-subgenual region in relation to higher levels of reflection. Parallel analyses were not significant for brooding or the RRS total score. These findings extend previous studies of rumination and identify a potential mechanistic model for symptom-based neuromodulation of rumination.

25,000 Years long seismic cycle in a slow deforming continental region of Mongolia.

The spatial distribution of large earthquakes in slowly deforming continental regions (SDCR) is poorly documented and, thus, has often been deemed to be random. Unlike in high strain regions, where seismic activity concentrates along major active faults, earthquakes in SDCR may seem to occur more erratically in space and time. This questions classical fault behavior models, posing paramount issues for seismic hazard assessment. Here, we investigate the M7, 1967, Mogod earthquake in Mongolia, a region recognized as a SDCR. Despite the absence of visible cumulative deformation at the ground surface, we found evidence for at least 3 surface rupturing earthquakes during the last 50,000 years, associated with a slip-rate of 0.06 ± 0.01 mm/year. These results show that in SDCR, like in faster deforming regions, deformation localizes on specific structures. However, the excessive length of return time for large earthquakes along these structures makes it more difficult to recognize earthquake series, and could conversely lead to the misconception that in SDCR earthquakes would be randomly located. Thus, our result emphasizes the need for systematic appraisal of the potential seismogenic structures in SDCR in order to lower the uncertainties associated with the seismogenic sources in seismic hazard models.

Isolation of Quartz Grains for Optically Stimulated Luminescence (OSL) Dating of Quaternary Sediments for Paleoenvironmental Research.

Optically stimulated luminescence (OSL) dating quantifies the time since mineral grains were deposited and shielded from additional light or heat exposure, which effectively resets the luminescence clock. The systematics of OSL dating is based on the dosimetric properties of common minerals, like quartz and feldspar. The acquired luminescence with exposure to natural ionizing radiation after burial provides a depositional age for many Quaternary sedimentary systems, spanning the past 0.5 Ma. This contribution details the procedures for separating pure quartz grains of a known range of particle sizes to facilitate luminescence analysis with small or single grain aliquots. Specifically, protocols are given for the needed data and interpretations for effective OSL dating of terrestrial sediment cores or sample tubes from exposures. These cores, 5-20 m long in 1.2 m sections, are split lengthwise and crown-cut leaving 80% of core volume undisturbed, which facilitates sampling of light-protected sediment for OSL dating deep within the core. Sediment samples are then subjected to a series of physical separations to obtain a certain grain-size interval (e.g., 150-250 µm). Magnetic minerals are removed in wet and dry states using magnets. A series of chemical digestions starts with soaking in H2O2 to remove organic matter, followed by HCl exposure to remove carbonate minerals, followed by density separation. Subsequently, grains are soaked in HF for 80 min and after in HCl to render solely quartz grains. The mineralogic purity (>99%) of the quartz extract is quantified with grain petrographic assessment and Raman spectroscopy. Repeating this quartz isolation procedure may be necessary with sediment that contains <15% quartz grains. Excitation of the purified quartz grains by LED-derived blue and IR light allows calculations of the fast and IR depletion ratios, which are metrics to assess the dominance of luminescence emissions from quartz.

Electrophysiological predictors and indicators of contingency management treatment response: Rationale and design for the ways of rewarding abstinence project (WRAP).

BACKGROUND: Electrophysiological measures can predict and reflect substance use treatment response. Veterans are disproportionately affected by disorders of addiction; cocaine use disorder (CUD) being particularly problematic due to high relapse rates and the absence of approved pharmacotherapies. Prize-based Contingency Management (PBCM) is an evidence-based behavioral intervention for CUD, involving incentives for cocaine abstinence but treatment response is variable. Measurement-based adaptation of PBCM has promise to improve effectiveness but remains to be usefully developed. METHODS: This trial aims to determine if individuals with distinct neurocognitive profiles differentially benefit from one of two existing versions of PBCM. CUD patients will be randomized into treatment-as-usual or 12-weeks of PBCM using either monetary or tangible prize incentives. Prior to randomization, EEG will be used to assess response to monetary versus tangible reward; EEG and cognitive-behavioral measures of working memory, cognitive control, and episodic future thinking will also be acquired. Substance use and treatment engagement will be monitored throughout the treatment interval and assessments will be repeated at post-treatment. DISCUSSION: Results of this trial may elucidate individual differences contributing to PBCM treatment response and reveal predictors of differential benefits from existing treatment variants. The design also affords the opportunity to evaluate treatment-related changes in neurocognitive functioning over the course of PBCM. Our model posits that PBCM scaffolds future-oriented goal representation and self-control to support abstinence. Individuals with poorer functioning may be less responsive to abstract monetary reward and will therefore achieve better outcomes with respect to abstinence and treatment engagement when tangible incentives are utilized.

Police transport of firearm-injured patients-more often and more injured.

BACKGROUND: Police transport (PT) of penetrating trauma patients decreases the time between injury and trauma center arrival. Our study objective was to characterize trends in the rate of PT and its impact on mortality. We hypothesized that PT is increasing and that these patients are more injured. METHODS: We conducted a single-center, retrospective cohort study of adult (≥18 years) patients presenting with gunshot wounds (GSWs) to a level 1 center from 2012 to 2018. Patients transported by police or ambulance (emergency medical service [EMS]) were included. The association between mode of transport (PT vs. EMS) and mortality was evaluated using χ2, t tests, Mann-Whitney U tests, and logistic regression. RESULTS: Of 2,007 patients, there were 1,357 PT patients and 650 EMS patients. Overall in-hospital mortality was 23.7%. The rate of GSW patients arriving by PT increased from 48.9% to 78.5% over the study period (p < 0.001). Compared with EMS patients, PT patients were sicker on presentation with lower initial systolic blood pressure (98 vs. 110, p < 0.001), higher Injury Severity Score (median [interquartile range], 10 [2-75] vs. 9 [1-17]; p < 0.001) and more bullet wounds (3.5 vs. 2.9, p < 0.001). Police-transported patients more frequently underwent resuscitative thoracotomy (19.2% vs. 10.0%, p < 0.001) and immediate surgical exploration (31.3% vs. 22.6%, p < 0.001). There was no difference in adjusted in-hospital mortality between transport groups. Of patients surviving to discharge, PT patients had higher Injury Severity Score (9.6 vs. 8.3, p = 0.004) and lower systolic blood pressure on arrival (126 vs. 130, p = 0.013) than EMS patients. CONCLUSION: Police transport of GSW patients is increasing at our urban level 1 center. Compared with EMS patients, PT patients are more severely injured but have similar in-hospital mortality. Further study is necessary to understand the impact of PT on outcomes in specific subsets in penetrating trauma patients. LEVEL OF EVIDENCE: Epidemiological, level III.

Early human impacts and ecosystem reorganization in southern-central Africa.

Modern Homo sapiens engage in substantial ecosystem modification, but it is difficult to detect the origins or early consequences of these behaviors. Archaeological, geochronological, geomorphological, and paleoenvironmental data from northern Malawi document a changing relationship between forager presence, ecosystem organization, and alluvial fan formation in the Late Pleistocene. Dense concentrations of Middle Stone Age artifacts and alluvial fan systems formed after ca. 92 thousand years ago, within a paleoecological context with no analog in the preceding half-million-year record. Archaeological data and principal coordinates analysis indicate that early anthropogenic fire relaxed seasonal constraints on ignitions, influencing vegetation composition and erosion. This operated in tandem with climate-driven changes in precipitation to culminate in an ecological transition to an early, pre-agricultural anthropogenic landscape.

Deep Learning Algorithm for Automated Cardiac Murmur Detection via a Digital Stethoscope Platform.

Background Clinicians vary markedly in their ability to detect murmurs during cardiac auscultation and identify the underlying pathological features. Deep learning approaches have shown promise in medicine by transforming collected data into clinically significant information. The objective of this research is to assess the performance of a deep learning algorithm to detect murmurs and clinically significant valvular heart disease using recordings from a commercial digital stethoscope platform. Methods and Results Using >34 hours of previously acquired and annotated heart sound recordings, we trained a deep neural network to detect murmurs. To test the algorithm, we enrolled 962 patients in a clinical study and collected recordings at the 4 primary auscultation locations. Ground truth was established using patient echocardiograms and annotations by 3 expert cardiologists. Algorithm performance for detecting murmurs has sensitivity and specificity of 76.3% and 91.4%, respectively. By omitting softer murmurs, those with grade 1 intensity, sensitivity increased to 90.0%. Application of the algorithm at the appropriate anatomic auscultation location detected moderate-to-severe or greater aortic stenosis, with sensitivity of 93.2% and specificity of 86.0%, and moderate-to-severe or greater mitral regurgitation, with sensitivity of 66.2% and specificity of 94.6%. Conclusions The deep learning algorithm's ability to detect murmurs and clinically significant aortic stenosis and mitral regurgitation is comparable to expert cardiologists based on the annotated subset of our database. The findings suggest that such algorithms would have utility as front-line clinical support tools to aid clinicians in screening for cardiac murmurs caused by valvular heart disease. Registration URL: https://clinicaltrials.gov; Unique Identifier: NCT03458806.

The Use of Integra Dermal Regeneration Templates and Cortical Bone Fenestrations over Exposed Tibia.

We present the case of an 86-year-old woman who suffered full-thickness soft tissue loss secondary to degloving injury to the lower left limb, resulting in an exposed tibia. This patient underwent drilling to create artificial fenestrations in the cortical bone followed by placement of Integra dermal regeneration template. The technique of drilling fenestrations to expose underlying vasculature of cortical bone has not previously been described in its relationship with Integra dermal regeneration templates in large degloving injuries of the lower limb. This technique enabled us to perform earlier skin grafting and ultimately resulted in complete and timely wound closure. We present this case as a comparable alternative treatment in cases of reconstructive surgery secondary to severe burns or trauma to reduce the time required for successful wound closure over exposed bone in full-thickness tissue loss injuries of the lower limb.

Evaluating effects of episodic future thinking on valuation of delayed reward in cocaine use disorder: a pilot study.

Background: Episodic future thinking (EFT; i.e., envisioning oneself in future contexts) has been demonstrated to reduce discounting of future reward in healthy adults. While this approach has the potential to support future-oriented decision-making in substance use recovery, the impact of EFT on discounting behavior in illicit stimulant users has not yet been evaluated.Objectives: This pilot study aimed to (1) assess the feasibility of utilizing EFT methods in individuals with cocaine use disorder (CUD) and (2) conduct preliminary measurement of the EFT effect on discounting behavior in this population.Methods: Eighteen treatment-seeking individuals with CUD (17 males) were interviewed about positive and neutral events expected to occur at a range of future latencies. Future event information identified by participants was subsequently included on a subset of trials in an intertemporal choice task to promote EFT; within-subject differences in discounting between standard and EFT conditions were evaluated.Results: Participants identified relevant events and demonstrated decreased discounting of future reward when event descriptors were included (relative to discounting without event descriptors; p = .039). It was further noted that most events identified by participants were goals, rather than plans or significant dates.Conclusion: While methods previously used to study the effect of EFT on discounting behavior in healthy individuals are also effective in individuals with CUD, methodological factors - including types of events identified - should be carefully considered in future work. These preliminary findings suggest that EFT can reduce impulsive decision-making in cocaine use disorder and may therefore have therapeutic value.

A longitudinal characterization of sex-specific somatosensory and spatial memory deficits in HIV Tg26 heterozygous mice.

The pathogenesis of human immunodeficiency virus associated neurological disorders is still not well understood, yet is known to result in neurological declines despite combination anti-retroviral therapy. HIV-1 transgenic (Tg26) mice contain integrated non-infectious HIV-1 proviral DNA. We sought to assess the integrity of neurocognitive function and sensory systems in HIV-1 Tg26 mice using a longitudinal design, in both sexes, to examine both age- and sex-related disease progression. General neurological reflexive testing showed only acclimation to repeated testing by all groups. Yet, at 2.5 months of age, female Tg26 +/- mice showed hyposensitivity to noxious hot temperatures, compared to wild types (both sexes) and male Tg26 +/- mice, that worsened by 10 months of age. Female Tg26 +/- mice had short-term spatial memory losses in novel object location memory testing at 2.5 and 7 months, compared to female wild types; changes not observed in male counterparts. Female Tg26 +/- mice showed mild learning deficits and short- and long-term spatial memory deficits in olfactory and visually cued Barnes Maze testing at 3 months of age, yet greater learning and memory deficits by 8 months. In contrast, male Tg26 +/- mice displayed no learning deficits and fewer spatial memory deficits (mainly heading errors in nontarget holes). Thus, greater sex-specific temperature hyposensitivity and spatial memory declines were observed in female HIV Tg26 +/- mice, than in male Tg26 +/- mice, or their wild type littermates, that increased with aging. Additionally, tibial bones were examined using ex vivo micro-CT after tissue collection at 11 months. Sex-dependent increases in bone volume and trabecular number were seen in males, matching their greater weights at this age. These results indicate that HIV-1 Tg26 mice is a promising model in which to study neuropathic mechanisms underlying peripheral pathology as well as cognitive deficits seen with HIV.

"I's" on the prize: A systematic review of individual differences in Contingency Management treatment response.

Contingency Management is an evidence-based treatment for substance use disorders with strong potential for measurement-based customization. Previous work has examined individual difference factors in Contingency Management treatment response of potential relevance to treatment targeting and adaptive implementation; however, a systematic review of such factors has not yet been conducted. Here, we summarize and evaluate the existing literature on patient-level predictors, mediators, and moderators of Contingency Management treatment response in stimulant and/or opioid using outpatients - clinical populations most frequently targeted in Contingency Management research and clinical practice. Our search strategy identified 648 unique, peer-reviewed publications, of which 39 met full inclusion criteria for the current review. These publications considered a variety of individual difference factors, including (1) motivation to change and substance use before and during treatment (8/39 publications), (2) substance use comorbidity and chronicity (8/39 publications), (3) psychiatric comorbidity and severity (8/39 publications), (4) medical, legal, and sociodemographic considerations (15/39 publications), and (5) cognitive-behavioral variables (1/39 publications). Contingency Management was generally associated with improved treatment outcomes (e.g., longer periods of continuous abstinence, better retention), regardless of individual difference factors; however, specific patient-level characteristics were associated with either an enhanced (e.g., more previous treatment attempts, history of sexual abuse, diagnosis of antisocial personality disorder) or diminished (e.g., complex post-traumatic stress symptoms, pretreatment benzodiazepine use) response to Contingency Management. Overall, the current literature is limited but existing evidence generally supports greater benefits of Contingency Management in patients who would otherwise have a poorer prognosis in standard outpatient care. It was also identified that the majority of previous work represents a posteriori analysis of pre-existing clinical samples and has therefore rarely considered pre-specified, hypothesis-driven individual difference factors. We therefore additionally highlight patient-level factors that are currently understudied, as well as promising future directions for measurement-based treatment adaptations that may directly respond to patient traits and states to improve Contingency Management effectiveness across individuals and over time.

Morphological characteristics of preparator air-scribe marks: Implications for taphonomic research.

Taphonomic analyses of bone-surface modifications can provide key insights into past biotic involvement with animal remains, as well as elucidate the context(s) of other biostratinomic (pre-burial) processes, diagenesis, excavation, preparation and storage. Such analyses, however, first require researchers to rigorously disambiguate between continuums of damage morphologies prior to attributing individual marks to specific actors and effectors (e.g., carnivore tooth, stone tool cutting edge, etc.). To date, a number of bone-modifying agents have been identified, and criteria for identifying their traces have been published. Relatively little research, however, has focused on bone-surface modifications imparted during specimen preparation. Herein we report that air scribes, small pneumatic tools commonly used for preparation in museum contexts, can generate unintentional marks that may mimic surficial modification caused by carnivores. To aid investigators in assessing the hypothesis that a mark in question is derived from air-scribe preparation activities, we provide high-resolution, detailed morphological information imaged with scanning electron microscopy (SEM). The main diagnostic characteristic of air-scribe damage is the occurrence of sequential, variously spaced, sub-millimeter scallop-like stepped bone removals. This morphology can resemble damage imparted by carnivore teeth. In contrast to marks produced by trampling, stone tools and carnivores, however, no continuous internal features, such as linear microstriations, were observed within grooves produced by the air scribe. Thus, the presence of such features can be used to disprove an air-scribe origin. A culmination of the morphological criteria presented herein, cross-cutting relationships with other surficial features (e.g., diagenetic discoloration, weathering textures), the position of occurrence, and an overall contextual framework for the assemblage is suggested for accurate identification of such traces. The ability to recognize or disprove air-scribe damage will allow researchers to confidently proceed with interpreting past biological and sedimentological interactions with animal remains.

Pre-Clovis projectile points at the Debra L. Friedkin site, Texas-Implications for the Late Pleistocene peopling of the Americas.

Lanceolate projectile points of the Clovis complex and stemmed projectile points of the Western Stemmed Tradition first appeared in North America by ~13 thousand years (ka) ago. The origin, age, and chronological superposition of these stemmed and lanceolate traditions are unclear. At the Debra L. Friedkin site, Texas, below Folsom and Clovis horizons, we find stemmed projectile points dating from ~13.5 to ~15.5 ka ago, with a triangular lanceolate point form appearing ~14 ka ago. The sequential relationship of stemmed projectile points followed by lanceolate forms suggests that lanceolate points are derived from stemmed forms or that they originated from two separate migrations into the Americas.

Effect of Repetitive Transcranial Magnetic Stimulation on Treatment-Resistant Major Depression in US Veterans: A Randomized Clinical Trial.

Importance: Treatment-resistant major depression (TRMD) in veterans is a major clinical challenge given the high risk for suicidality in these patients. Repetitive transcranial magnetic stimulation (rTMS) offers the potential for a novel treatment modality for these veterans. Objective: To determine the efficacy of rTMS in the treatment of TRMD in veterans. Design, Setting, and Participants: A double-blind, sham-controlled randomized clinical trial was conducted from September 1, 2012, to December 31, 2016, in 9 Veterans Affairs medical centers. A total of 164 veterans with TRD participated. Interventions: Participants were randomized to either left prefrontal rTMS treatment (10 Hz, 120% motor threshold, 4000 pulses/session) or to sham (control) rTMS treatment for up to 30 treatment sessions. Main Outcomes and Measures: The primary dependent measure of the intention-to-treat analysis was remission rate (Hamilton Rating Scale for Depression score ≤10, indicating that depression is in remission and not a clinically significant burden), and secondary analyses were conducted on other indices of posttraumatic stress disorder, depression, hopelessness, suicidality, and quality of life. Results: The 164 participants had a mean (SD) age of 55.2 (12.4) years, 132 (80.5%) were men, and 126 (76.8%) were of white race. Of these, 81 were randomized to receive active rTMS and 83 to receive sham. For the primary analysis of remission, there was no significant effect of treatment (odds ratio, 1.16; 95% CI, 0.59-2.26; P = .67). At the end of the acute treatment phase, 33 of 81 (40.7%) of those in the active treatment group achieved remission of depressive symptoms compared with 31 of 83 (37.4%) of those in the sham treatment group. Overall, 64 of 164 (39.0%) of the participants achieved remission. Conclusions and Relevance: A total of 39.0% of the veterans who participated in this trial experienced clinically significant improvement resulting in remission of depressive symptoms; however, there was no evidence of difference in remission rates between the active and sham treatments. These findings may reflect the importance of close clinical surveillance, rigorous monitoring of concomitant medication, and regular interaction with clinic staff in bringing about significant improvement in this treatment-resistant population. Trial Registration: ClinicalTrials.gov Identifier: NCT01191333.

Regional cerebral blood flow predictors of relapse and resilience in substance use recovery: A coordinate-based meta-analysis of human neuroimaging studies.

BACKGROUND: Predicting relapse vulnerability can inform level-of-care and personalized substance use treatment. Few reliable predictors of relapse risk have been identified from traditional clinical, psychosocial, and demographic variables. However, recent neuroimaging findings highlight the potential prognostic import of brain-based signals, indexing the degree to which neural systems have been perturbed by addiction. These proposed "neuromarkers" forecast the likelihood, severity, and timing of relapse but the reliability and generalizability of such effects remains to be established. METHODS: Activation likelihood estimation was used to conduct a preliminary quantitative, coordinate-based meta-analysis of the addiction neuroprediction literature; specifically, studies wherein baseline measures of regional cerebral blood flow were prospectively associated with substance use treatment outcomes. Consensus patterns of activation associated with relapse vulnerability (greater activation predicts poorer outcomes) versus resilience (greater activation predicts improved outcomes) were specifically investigated. RESULTS: Twenty-four eligible studies yielded 134 foci, representing 923 subjects. Consensus activation was identified in right putamen and claustrum (p < .05, cluster-corrected) in relation to positive and negative treatment outcomes - likely reflecting variability in measurement context (e.g., task, sample characteristics) across datasets. A single cluster in rostral-ventral anterior cingulate cortex (rACC) was associated with relapse resilience, specifically (p < .05, cluster-corrected); no significant vulnerability-related clusters were identified. CONCLUSIONS: Right putamen activation has been associated with relapse vulnerability and resilience, while increased baseline rACC activation has been consistently associated with improved treatment outcomes. Methodological heterogeneity within the existing literature, however, limits firm conclusions and future work will be necessary to confirm and clarify these results.

Repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) Veteran patients: study protocol for a randomized controlled trial.

BACKGROUND: Evaluation of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depression (TRMD) in Veterans offers unique clinical trial challenges. Here we describe a randomized, double-blinded, intent-to-treat, two-arm, superiority parallel design, a multicenter study funded by the Cooperative Studies Program (CSP No. 556) of the US Department of Veterans Affairs. METHODS: We recruited medical providers with clinical expertise in treating TRMD at nine Veterans Affairs (VA) medical centers as the trial local investigators. We plan to enroll 360 Veterans diagnosed with TRMD at the nine VA medical centers over a 3-year period. We will randomize participants into a double-blinded clinical trial to left prefrontal rTMS treatment or to sham (control) rTMS treatment (180 participants each group) for up to 30 treatment sessions. All participants will meet Diagnostic and statistical manual of mental disorders, 4 th edition (DSM-IV) criteria for major depression and will have failed at least two prior pharmacological interventions. In contrast with other rTMS clinical trials, we will not exclude Veterans with posttraumatic stress disorder (PTSD) or history of substance abuse and we will obtain detailed history regarding these disorders. Furthermore, we will maintain participants on stable anti-depressant medication throughout the trial. We will evaluate all participants on a wide variety of potential predictors of treatment response including cognitive, psychological and functional parameters. DISCUSSION: The primary dependent measure will be remission rate (Hamilton Rating Scale for Depression (HRSD24) ≤ 10), and secondary analyses will be conducted on other indices. Comparisons between the rTMS and the sham groups will be made at the end of the acute treatment phase to test the primary hypothesis. The unique challenges to performing such a large technically challenging clinical trial with Veterans and potential avenues for improvement of the design in future trials will be described. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01191333 . Registered on 26 August 2010. This report is based on the protocol version 4.6 amended in February 2016. All items from the World Health Organization Trial Registration Data Set are listed in Appendix A.

Groundwater sapping as the cause of irreversible desertification of Hunshandake Sandy Lands, Inner Mongolia, northern China.

In the middle-to-late Holocene, Earth's monsoonal regions experienced catastrophic precipitation decreases that produced green to desert state shifts. Resulting hydrologic regime change negatively impacted water availability and Neolithic cultures. Whereas mid-Holocene drying is commonly attributed to slow insolation reduction and subsequent nonlinear vegetation-atmosphere feedbacks that produce threshold conditions, evidence of trigger events initiating state switching has remained elusive. Here we document a threshold event ca. 4,200 years ago in the Hunshandake Sandy Lands of Inner Mongolia, northern China, associated with groundwater capture by the Xilamulun River. This process initiated a sudden and irreversible region-wide hydrologic event that exacerbated the desertification of the Hunshandake, resulting in post-Humid Period mass migration of northern China's Neolithic cultures. The Hunshandake remains arid and is unlikely, even with massive rehabilitation efforts, to revert back to green conditions.