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The United Nations Decade of Ocean Science for Sustainable Development requires that all of the Actions it endorses have concrete plans to involve stakeholders in the co-creation of ocean science. As a result, we have a unique opportunity to test different approaches to stakeholder engagement to see what works and what does not. Here, we feature short essays in the “Food for Thought” series in which leaders from Decade-endorsed Actions describe how they plan to incorporate stakeholders in the co-design, co-production, and co-delivery of ocean science and how they will measure whether these approaches were successful. We also invited submissions to the journal’s “Stories from the Front Lines” series, in which authors were asked to share unvarnished accounts of the lessons learned from previous efforts to co-design ocean science. We hope that these initial articles will be the beginning of an ongoing series in which new Decade Actions will also document their plans to implement, monitor, and measure the success or failure of these approaches.

Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Valentine’s influential norm-based multidimensional face-space model (nMDFS) predicts that perceived distinctiveness increases with distance to the norm. Occipito-temporal event-related potentials (ERPs) have been recently shown to respond selectively to variations in distance-to-norm (P200) or familiarity (N250, late negativity), respectively (Wuttke & Schweinberger, 2019). Despite growing evidence on interindividual differences in face perception skills at the behavioral level, little research has focused on their electrophysiological correlates. To reveal potential interindividual differences in face spaces, we contrasted high and low performers in face recognition in regards to distance-to-norm (P200) and familiarity (N250). We replicated both the P200 distance-to-norm and the N250 familiarity effect. Importantly, we observed: i) reduced responses in low compared to high performers of face recognition, especially in terms of smaller distance-to-norm effects in the P200, possibly indicating less ‘expanded’ face spaces in low compared to high performers; ii) increased N250 responses to familiar original faces in high performers, suggesting more robust face identity representations. In summary, these findings suggest the contribution of both early norm-based face coding and robust face representations to individual face recognition skills, and indicate that ERPs can offer a promising route to understand individual differences in face perception and their neurocognitive correlates. - Introduction: How are Known Faces Mentally Encoded? Valentine’s Norm-based Multidimensional Face-space Model - Individual Differences in Face Recognition and Differences in the MDFS - The Present Study - Methods -- General Procedure -- Screening Phase -- Testing Phase - Results -- Screening tests -- Behavioral data -- Electrophysiological data - Discussion -- Overview and replication of past research -- General Vision Differences Contribute to Face Recognition Performance -- Differences in Neural Effects of DTN and Familiarity between High and Low Performers -- Neural Individual Differences in Face Processing across Milliseconds - Conclusions

The axon initial segment (AIS) constitutes not only the site of action potential initiation, but also a hub for activity-dependent modulation of output generation. Recent studies shedding light on AIS function used predominantlypost hocapproaches since no robust murinein vivolive reporters exist. Here, we introduce a reporter line in which the AIS is intrinsically labeled by an ankyrin-G-GFP fusion protein activated by Cre recombinase, tagging the nativeAnk3gene. Using confocal, superresolution, and two-photon microscopy as well as whole-cell patch-clamp recordingsin vitro, ex vivo, andin vivo, we confirm that the subcellular scaffold of the AIS and electrophysiological parameters of labelled cells remain unchanged. We further uncover rapid AIS remodeling following increased network activity in this model system, as well as highly reproduciblein vivolabeling of AIS over weeks. This novel reporter line allows longitudinal studies of AIS modulation and plasticityin vivoin real time and thus provides a unique approach to study subcellular plasticity in a broad range of applications.

To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) contribute to protection against several pathogens. In this study, we demonstrated that conjugation of HIV Envelope (Env) antigen gp120 to a self-assembling nanofiber material named Q11 induced antibodies with higher breadth and functionality when compared to soluble gp120. Immunization with Q11-conjugated gp120 vaccine (gp120-Q11) demonstrated higher tier 1 neutralization, ADCP, and ADCC as compared to soluble gp120. Moreover, Q11 conjugation altered the Fc N-glycosylation profile of antigen-specific antibodies, leading to a phenotype associated with increased ADCC in animals immunized with gp120-Q11. Thus, this nanomaterial vaccine strategy can enhance non-neutralizing antibody functions possibly through modulation of immunoglobulin G Fc N-glycosylation.

Adaptation in human and natural systems has received growing attention in sustainability scholarship. Co-adaptation, when coupled human and natural systems (CHANSs) adapt in congruence, is receiving much less attention. Not only are various forms of co-adaptation difficult to disentangle, adaptations are also conceptualized very differently by scholars of human and natural systems. One aspect of adaptation that scholars agree on, however, is that it is first and foremost a change. We offer a new transdisciplinary typology of the four most basic types of change, internally and externally driven non-structural and structural changes, that bridges perspectives in the natural and social sciences and through which we introduce new categories of adaptations and forms of co-adaptation in CHANSs. We first describe the typology’s foundations and its four types of change. We then organize forms of adaptation in human and natural systems according to the types of change they exhibit to identify new categories of adaptations and forms of co-adaptation. Finally, we illustrate the application of the new categories and forms in a real-world CHANS—the privately managed Northwoods in the Upper Midwest, USA. This new typology paves the way for robust and cross-disciplinary research on CHANSs.

Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is a clinically and histologically distinct variant of inflammatory myofibroblastic tumor that is characterized by an aggressive clinical course and dismal prognosis (1). Histologically, EIMS is composed of sheets of rounded or epithelioid cells with vesicular nuclei, large nucleoli, and eosinophilic to amphophilic cytoplasm, that is often set in a myxoid stroma rich in inflammatory cells. A minor spindle cell component is usually present. Most EIMS harbor RANBP2-ALK or RRBP1-ALK gene fusions and only a single putative case harboring an alternate EML4-ALK fusion has been reported (2-3). Notably, the ALK immunostaining pattern varies depending on ALK fusion partner; RANBP2-ALK is associated with nuclear membranous pattern while RRBP1-ALK shows a perinuclear accentuated cytoplasmic pattern. EIMS typically affects male patients and shows a striking predilection for the abdominal cavity. Exceptionally rare cases have been reported in the thoracic cavity (3 in lung/pleura) and pelvic cavity (1 in ovary) (4-7). To our knowledge, EIMS has not been reported outside the ventral cavity.

Pregnancy significantly elevates the risk of developing severe viral diseases, which can have a detrimental effect on fetal development and increases maternal mortality. In addition, certain viruses can be transmitted vertically from mother to babies, either in utero, during delivery, or postnatally during breastfeeding, resulting in congenital or neonatal diseases and associated sequelae. While neonates are highly susceptible to viral infections and severe disease outcomes, due to the immaturity of their developing immune system, virus-specific maternal antibodies transferred either trans-placentally or via breast milk provide protection to infants against intestinal, respiratory, or systemic infections, during the first months of life. Thus, maternal prenatal immunization is important not only to protect pregnant women from viral diseases, but also to prevent infection and/or improve disease outcomes for the fetuses and neonates via passively transferred antibodies. In this review, we discuss the protective role of maternal antibodies against three categories of viruses: (i) viruses that cause severe maternal disease outcomes with mainly indirect consequences to the fetus (e.g. SARS-CoV-2, influenza, DENV, filovirus), (ii) those that are vertically transmitted from mother to their infants and cause congenital diseases (e.g. HIV, ZIKV and CMV), and (iii) those that cause elevated disease severity among neonates and infants postnatally (e.g. RSV, Rotavirus, Norovirus, HSV and HBV). Furthermore, we review relevant pre-clinical animal models that can be employed to develop novel immunization strategies against these viruses to enhance protection of pregnant women and their babies.

Background This study characterizes the outcomes and complications of surgical reconstruction of distal radioulnar joint (DRUJ) instability using the extensor retinaculum (Herbert sling). Our hypothesis was that extensor retinaculum reconstruction is a reliable method of DRUJ stabilization in adolescents. Methods This was a retrospective study of pediatric patients treated surgically using the Herbert sling for DRUJ instability at a single institution. We identified 22 subjects who underwent surgery at an average of 16.2 years of age (range, 12-18 years). Medical records and available imaging were reviewed for all subjects, and patients were contacted to participate in the prospective completion of the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire. Results Preoperative symptoms were more commonly pain (95%) than feelings of DRUJ instability (45%), although 100% had instability on physical examination. Eight (36%) patients demonstrated limited supination preoperatively. Twenty-one subjects (95%) noted prior injury to that wrist, 15 of which were distal radius fractures. Surgery consisted of stabilization of the DRUJ using extensor retinaculum, in concert with other procedures to address all potential causes of wrist pain. Postoperatively, DRUJ stability was maintained in 21 of 22 subjects. Of the 12 patients who provided functional outcome scores, median QuickDASH score was 7.6 (range, 0-45). Conclusions Distal radioulnar joint instability in adolescents is often preceded by fracture of the distal radius. Surgeons must maintain a high level of suspicion to appropriately diagnose DRUJ instability, which is often not an isolated pathoanatomical problem. The Herbert sling technique using extensor retinaculum can successfully confer DRUJ stability in this population.

PURPOSE OF REVIEW: In the absence of antiretroviral therapy (ART), more than 50% of perinatally HIV infected children die by two years of age. Early ART from infancy is therefore a global recommendation and significantly improves immune health, child survival and disease outcome. However, even early treatment does not prevent or eradicate the latent reservoir necessitating life-long ART. Adherence to life-long ART is challenging for children and longstanding ART during chronic HIV infection led to higher risks of non-AIDS co-morbidities and virologic failure in infected children. Thus, HIV-infected children are an important population for consideration for immune-based interventions to achieve ART-free remission and functional cure. This review summarizes how the uniqueness of the early life immune system can be harnessed for the development of ART-free remission and functional cure, which means complete virus control in absence of ART. In addition, recent advances in therapeutics in the HIV cure field and their potential for the treatment of pediatric HIV infections are discussed. RECENT FINDINGS: Preclinical studies and clinical trials demonstrated that immune-based interventions target HIV replication, limit size of virus reservoir, maintain virus suppression, and delay time to virus rebound. However, these studies have been performed so far only in carefully selected HIV-infected adults, highlighting the need to evaluate the efficacy of immune-based therapeutics in HIV-infected children and to design interventions tailored to the early life maturing immune system. SUMMARY: Immune-based therapeutics alone or in combination with ART should be actively explored as potential strategies to achieve viral remission and functional cure in HIV-infected pediatric populations.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique to treat psychiatric disorders, such as obsessive-compulsive disorder (OCD). However, the rTMS response varies across subjects.OBJECTIVE/HYPOTHESIS: We hypothesize that baseline network properties of the rTMS target may help understand this variation and predict response.METHODS: Excitatory rTMS to the dorsolateral prefrontal cortex (dlPFC) was applied in 19 unmedicated OCD patients, while inhibitory dlPFC-rTMS was applied in 17 healthy controls. The vertex was used as an active control target (19 patients, 18 controls). The rTMS response was operationalized as the individual change in state distress rating during an emotion regulation task. At baseline, subjects underwent resting-state functional MRI. The brain network was constructed by calculating wavelet coherence between regional activity of regions in the Brainnetome atlas. Local and integrative static connectivity and the dynamic network role of the target were calculated. Baseline target region network features were non-parametrically correlated to rTMS response.RESULTS: In the dlPFC-stimulated patients, greater local connectivity (Kendall's Tau = -0.415, p = 0.013) and less promiscuous role of the target (Kendall's Tau = 0.389, p = 0.025) at baseline were related to greater distress reduction after excitatory rTMS. There were no significant associations in healthy subjects nor in the active control stimulated patients.CONCLUSIONS: Pre-treatment network topological indices predict rTMS-induced emotional response changes in OCD, such that greater baseline resting-state local connectivity and less temporal integration of the target region imply greater stimulation effects. These results may lead the way towards personalized neuromodulation in OCD.

Women of childbearing age are three times more likely to contract HIV infection than their male counterparts. Poor HIV testing rates coupled with low adherence to antiretroviral therapy (ART) result in a high risk of mother-to-infant HIV transmission, especially during the breastfeeding period.

Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital infection has been hindered by limited knowledge of the immune responses that protect against placental HCMV transmission in maternal primary and nonprimary infection. To identify protective antibody responses, we measured anti-HCMV IgG binding and anti-viral functions in maternal and cord blood sera from HCMV transmitting (n=41) and non- transmitting (n=40) mother-infant dyads identified via a large U.S.-based public cord blood bank. In a predefined immune correlate analysis, maternal monocyte-mediated antibody-dependent cellular phagocytosis (ADCP) and high avidity IgG binding to HCMV envelope glycoproteins were associated with decreased risk of congenital HCMV infection. Moreover, HCMV-specific IgG engagement of FcγRI and FcγRIIA, which mediate non-neutralizing antibody responses, was enhanced in non-transmitting mother-infant dyads and strongly correlated with ADCP. These findings suggest that Fc effector functions including ADCP protect against placental HCMV transmission. Taken together, our data indicate that future active and passive immunization strategies to prevent congenital HCMV infection should target Fc-mediated non-neutralizing antibody responses.

Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.

Improved access to antiretroviral therapy and antenatal care have significantly reduced in-utero and peri-partum mother-to-child HIV transmission. However, as breastmilk transmission of HIV still occurs at an unacceptable rate there remains a need to develop an effective vaccine for the pediatric population.Previously, we compared different HIV vaccine strategies, intervals, and adjuvants in infant rhesus macaques to optimize the induction of HIV envelope (Env)-specific antibodies with Fc-mediated effector function. Here, we tested the efficacy of an optimized vaccine regimen against oral SHIV acquisition in infant macaques. One group of 12 animals was immunized with 1086.c gp120 protein adjuvanted with 3M-052 in stable emulsion and Modified Vaccinia Ankara (MVA) virus vector expressing 1086.c HIV Env, while the control group (n=12) was immunized only with empty MVA. The first vaccine dose was given within 10 days of birth and booster doses were administered at weeks 6 and 12.The vaccine regimen induced Env-specific plasma IgG antibodies capable of antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). Beginning at week 15, infants were exposed orally to escalating doses of heterologous SHIV-1157(QNE)Y173H once a week until infected. Despite the induction of strong Fc-mediated antibody responses, the vaccine regimen did not reduce the risk of infection, time to acquisition, or peak viremia compared to controls. Our results suggest that the non-neutralizing Env-specific antibodies with Fc effector function elicited by this vaccine regimen were insufficient for protection against heterologous oral SHIV infection shortly after the final immunization.IMPORTANCEWomen of childbearing age are three times more likely to contract HIV infection than their male counterparts. Poor HIV testing rates coupled with low adherence to antiretroviral therapy (ART) result in a high risk of mother-to-infant HIV transmission, especially during the breastfeeding period. A preventative vaccine could curb pediatric HIV infections, reduce potential health sequalae, and prevent the need for lifelong ART in this population. The results of the current study imply that the HIV Env-specific IgG antibodies elicited by this candidate vaccine regimen, despite high magnitude of Fc-mediated effector function, but lack of neutralizing antibodies and polyfunctional T cell responses, were insufficient to protect infant rhesus macaques against oral virus acquisition.

Triangular fibrocartilage complex (TFCC) tears can cause ulnar-sided wrist pain in children and adolescents following acute rotational injury or prior distal radius fracture. Surgical treatment, guided by the Palmer classification, is considered after activity modification and occupational therapy. All concomitant wrist pathologies, such as distal radioulnar joint instability, ulnocarpal impaction, and distal radius malunion, must be recognized and addressed at the time of TFCC debridement or repair. This article reviews recent literature guiding clinical evaluation and surgical treatment of children and adolescents with TFCC injuries. The authors' techniques for arthroscopic-assisted outside-in repair of Palmer 1B and 1D tears are described.

BACKGROUND: Functional neuroimaging endophenotypes of obsessive-compulsive disorder (OCD) have been suggested during executive tasks. The purpose of this study was to investigate whether behavioral and neural responses during emotion processing and regulation also represent an endophenotype of OCD.METHODS: Forty-three unmedicated adult OCD patients, 19 of their unaffected siblings, and 38 healthy control participants underwent 3T functional magnetic resonance imaging during an emotion regulation task including neutral, fear-inducing, and OCD-related visual stimuli. Stimuli were processed during natural appraisal and during cognitive reappraisal, and distress ratings were collected after each picture. We performed between-group comparisons on task behavior and brain activation in regions of interest during emotion provocation and regulation.RESULTS: Siblings reported similar distress as healthy control participants during provocation, and significantly less than patients. There was no significant three-group difference in activation during fear provocation or regulation. Three-group comparisons showed that patients had higher amygdala and dorsomedial prefrontal cortex activation during OCD-related emotion provocation and regulation, respectively, while siblings were intermediate between patients and control participants but not significantly different from either. Siblings showed higher left temporooccipital activation (compared with both healthy control participants and patients) and higher frontolimbic connectivity (compared with patients) during OCD-related regulation.CONCLUSIONS: Unaffected siblings do not show the same distress and amygdala activation during emotional provocation as OCD patients. Siblings show distinct activation in a temporo-occipital region, possibly related to compensatory cognitive control. This suggests that emotion regulation is not a strong endophenotype for OCD. When replicated, this contributes to our understanding of familial risk and resilience for OCD.

The norm-based face space model (nMDFS) predicts that perceived typicality decreases with distance to the norm. Accordingly, an original face and its corresponding anti-face (deviating in exactly opposite direction from the norm) should inherit equivalent levels of typicality. Similarly, varying distance-to-norm (DTN, in absolute values) should have equivalent effects on typicality for both unfamiliar faces and their anti-faces. Here we reasoned that familiar faces would not follow this rule, due to the special nature of their mental representations. We investigated event-related brain potentials (ERPs) to familiar and unfamiliar faces and their anti-faces with different DTN (±0.33, ±0.66, and ±0.99). Across DTN, rated typicality was highest for original familiar faces, whereas all other face stimuli exhibited the expected gradual decrease of typicality with increasing DTN. ERPs showed pronounced DTN effects in the occipitotemporal P200 (190–260 ms), with progressively smaller amplitudes for faces with higher DTN, for all face types. By contrast, prominent effects of familiarity were found for the subsequent N250 (260–400 ms) and a late occipitotemporal negativity (LN, 400–800 ms). A large increase of occipitotemporal negativity was observed for original familiar faces versus their non-recognizable anti-faces. Analogous effects were small or absent for unfamiliar faces versus their anti-faces. These results confirm the N250 and LN as correlates of the processing of the identity of known faces, and show for the first time that the face-sensitive P200 is primarily modulated by DTN of a face in nMDFS.

Daily burden and clinical toxicities associated with antiretroviral therapy (ART) emphasize the need for alternative strategies to induce long-term human immunodeficiency virus (HIV) remission upon ART cessation. Broadly neutralizing antibodies (bNAbs) can both neutralize free virions and mediate effector functions against infected cells and therefore represent a leading immunotherapeutic approach. To increase potency and breadth, as well as to limit the development of resistant virus strains, it is likely that bNAbs will need to be administered in combination. It is therefore critical to identify bNAb combinations that can achieve robust polyfunctional antiviral activity against a high number of HIV strains. In this study, we systematically assessed the abilities of single bNAbs and triple bNAb combinations to mediate robust polyfunctional antiviral activity against a large panel of cross-clade simian-human immunodeficiency viruses (SHIVs), which are commonly used as tools for validation of therapeutic strategies targeting the HIV envelope in nonhuman primate models. We demonstrate that most bNAbs are capable of mediating both neutralizing and nonneutralizing effector functions against cross-clade SHIVs, although the susceptibility to V3 glycan-specific bNAbs is highly strain dependent. Moreover, we observe a strong correlation between the neutralization potencies and nonneutralizing effector functions of bNAbs against the transmitted/founder SHIV CH505. Finally, we identify several triple bNAb combinations comprising of CD4 binding site-, V2-glycan-, and gp120-gp41 interface-targeting bNAbs that are capable of mediating synergistic polyfunctional antiviral activities against multiple clade A, B, C, and D SHIVs. IMPORTANCE Optimal bNAb immunotherapeutics will need to mediate multiple antiviral functions against a broad range of HIV strains. Our systematic assessment of triple bNAb combinations against SHIVs will identify bNAbs with synergistic, polyfunctional antiviral activity that will inform the selection of candidate bNAbs for optimal combination designs. The identified combinations can be validated in vivo in future passive immunization studies using the SHIV challenge model.

Additional file 1: Table A1. Relative risk (95% CI) and PAF for four dimensions of social exclusion. Table A2. Overlap between social exclusion and four social factors (weighted percentages). Table A3. Relative risks (95% CI) for social factors with and without SE and differential effects.

Bentonite is a natural clay that is used in different industries as a desiccant, ion-exchange material, or additive to remove impurities. For example, marketed as healing clay and as protein-fining agent in wine, bentonite is expected to adsorb specific compounds while having no negative effects on the quality of the product in which it is used. In this study, 34 commercially available bentonites for different applications were selected and analyzed for their elemental composition, extraction of heavy metals, swelling behavior, and protein removal rate under conditions relevant to wine. The results indicate that bentonites can have a very variable composition that does not correlate with the intended use. The extraction of heavy metals is not directly related to the raw material and depends on swelling behavior and surface area of the clay. Interestingly, there is a similar degree of variability in swelling behavior among wine bentonites as there is for healing clays. This correlates with the protein removal rate but also with the extraction of iron, a transition metal that is known for its catalytic activity for oxidation reactions. Even though the protein removal rate is much higher than for other clays, bentonites that are marketed for wine show an extraction behavior that can have a negative effect on the final product.

Uncovering the sanctuaries of the long-lived HIV-1 reservoir is crucial to develop cure strategies. Pediatric immunity is distinct from that of adults, which may alter where the reservoir is established in infancy. Thus, it is important to utilize pediatric models to inform cure-directed approaches for HIV-1-infected children. We used an infant rhesus macaque model of HIV-1 infection via breastfeeding to identify key sites of viral persistence under antiretroviral therapy (ART). The gastrointestinal tract was found to be a site for low-level viral transcription during ART. We also show that naive CD4+ T cells harbored intact provirus and were a major contributor to blood and lymphoid reservoir size. This is particularly striking, as memory CD4+ T cells are generally regarded as the main source of latent HIV/simian immunodeficiency virus (SIV) infection of adult humans and rhesus macaques. Our findings highlight unique features of reservoir composition in pediatric infection that should be considered for eradication efforts., Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) continues to cause new pediatric cases of infection through breastfeeding, a setting where it is not always possible to initiate early antiretroviral therapy (ART). Without novel interventions that do not rely on daily ART, HIV-1-infected children face lifelong medications to control infection. A detailed analysis of virus persistence following breast milk transmission of HIV-1 and ART has not been performed. Here, we used infant rhesus macaques orally infected with simian/human immunodeficiency virus (SHIV) (SHIV.C.CH505) to identify cellular and anatomical sites of virus persistence under ART. Viral DNA was detected at similar levels in blood and tissue CD4+ T cells after a year on ART, with virus in blood and lymphoid organs confirmed to be replication competent. Viral RNA/DNA ratios were elevated in rectal CD4+ T cells compared to those of other sites (P ≤ 0.0001), suggesting that the gastrointestinal tract is an active site of virus transcription during ART-mediated suppression of viremia. SHIV.C.CH505 DNA was detected in multiple CD4+ T cell subsets, including cells with a naive phenotype (CD45RA+ CCR7+ CD95–). While the frequency of naive cells harboring intact provirus was lower than in memory cells, the high abundance of naive cells in the infant CD4+ T cell pool made them a substantial source of persistent viral DNA (approximately 50% of the total CD4+ T cell reservoir), with an estimated 1:2 ratio of intact provirus to total viral DNA. This viral reservoir profile broadens our understanding of virus persistence in a relevant infant macaque model and provides insight into targets for cure-directed approaches in the pediatric population. IMPORTANCE Uncovering the sanctuaries of the long-lived HIV-1 reservoir is crucial to develop cure strategies. Pediatric immunity is distinct from that of adults, which may alter where the reservoir is established in infancy. Thus, it is important to utilize pediatric models to inform cure-directed approaches for HIV-1-infected children. We used an infant rhesus macaque model of HIV-1 infection via breastfeeding to identify key sites of viral persistence under antiretroviral therapy (ART). The gastrointestinal tract was found to be a site for low-level viral transcription during ART. We also show that naive CD4+ T cells harbored intact provirus and were a major contributor to blood and lymphoid reservoir size. This is particularly striking, as memory CD4+ T cells are generally regarded as the main source of latent HIV/simian immunodeficiency virus (SIV) infection of adult humans and rhesus macaques. Our findings highlight unique features of reservoir composition in pediatric infection that should be considered for eradication efforts.

ObjectiveResponse inhibition has previously been suggested as an endophenotype for obsessive-compulsive disorder (OCD), evidenced by studies showing worse task performance, and altered task-related activation and connectivity. However, it’s unclear if these measures change following treatment.MethodsThirty-one OCD patients and 28 healthy controls performed a stop signal task during 3T functional magnetic resonance imaging before treatment, while 24 OCD patients and 17 healthy controls were rescanned one week and three months after concentrated exposure and response prevention over four consecutive days using Bergen 4-Day Format. To study changes over time we performed a longitudinal analysis on stop signal reaction time and task-related activation and amygdala connectivity during successful and failed inhibition.ResultsThere was no group difference in task performance. Before treatment, OCD patients compared to controls showed less inhibition-related activation in the right inferior frontal gyrus, and increased functional connectivity between the right amygdala and the right inferior frontal gyrus and pre-supplementary motor area. During error-processing, OCD patients versus controls showed less activation in the pre-SMA before treatment. These group differences did not change after treatment. Pre-treatment task performance, and brain activation and connectivity were unrelated to the degree of symptom improvement after treatment.ConclusionsInferior frontal gyrus hypoactivation and increased fronto-limbic connectivity are likely trait markers of OCD that remain after effective exposure therapy.

Supplemental material, Supplemental_Table_1_and_Table_2 for Radiographic Outcomes and Complications of Delayed Fixation of Distal Radius Fractures by Stella J. Lee, Derek S. Stenquist, Jamie E. Collins, Ariana N. Mora, Brett A. Teplitz, Philip E. Blazar and Brandon E. Earp in HAND

Over the past century, beech bark disease has dramatically altered the composition and structure of stands containing American beech (Fagus grandifolia). Management of beech bark disease has focused on reducing beech thickets and identifying resistant trees in aftermath forests. Beech leaf disease is a recently detected invasive disease, now also affecting beech forests. In 2019, a plot network was established in central North America to examine the extent of beech leaf disease spread and the severity of effects on trees and forests. Here, data from this plot network was used to determine the extent to which American beech is exposed to beech leaf disease, beech scale (Cryptococcus fagisuga), and beech bark disease (C. fagisuga and Neonectria spp. complex) in forests surrounding the Great Lakes in southwestern Ontario, northeastern Ohio, western Pennsylvania, and western New York. Beech leaf disease and scale were found to be well established, not only among sites but also in the different canopy layers. Beech bark disease was present, but occurrence was low. Pest accumulation differed between overstory and sapling layers. Beech leaf disease was the primary pest of saplings while both beech leaf disease and beech scale dominated in the overstory. Forest composition was similar throughout the study range; American beech, sugar maple, red maple, and white ash were abundant and common in the sapling and seedling layer. Few invasive plants were evident among saplings and seedlings. Sugar maple and red maple will likely fill small canopy gaps following beech decline or mortality. Intervention should be considered in stands with potential for increasing tree diversity or promoting beech leaf disease-resistant American beech trees to the overstory. New strategies are needed for beech conservation along with research to determine the extent of beech leaf disease resistance in American beech.

We followed an ERP-based approach to gain knowledge on the dependence and temporal order of two essential processes of face perception: attractiveness and gender. By combining a dual-choice task with a go/nogo-paradigm focusing on the LRP and N200-effect, we could estimate the processing times and onsets of both types of face processing. The analyses of the LRP revealed that gender aspects were processed much earlier than attractiveness. Whereas gender was already analysed 243.9 ms post-stimulus onset, attractiveness came into play 58.6 ms later, i.e. after a post-stimulus onset delay of 302.5 ms. This resulting pattern was mirrored by the analyses of the N200-effect, an effect available mainly frontally which is supposed to correlate with the inhibition of inappropriate responses. Taking the onset of the N200 effect as an estimator for the moment at which information has been processed sufficiently for task decision, we could trace the N200 effect at 152.0 ms for go/nogo-decision on gender, while not as early as 206.7 ms on attractiveness. In sum, processing of facial attractiveness seems to be based on gender-specific aesthetic pre-processing, for instance via activating gender-specific attractiveness prototypes which show focused processing of certain facial aspects.

Background Few population-based studies assess both invasive and in situ melanoma. We document all patients with a first biopsied melanoma in a general population in New Zealand (NZ). Methods All residents in a defined area of New Zealand with a biopsy showing a new primary invasive or in situ melanoma from 2010 to 2012 were identified, 974 patients; analysis used multivariate methods. Results Age-standardised incidence rates were 34.3 in females (F) and 41.4 in males (M) for invasive, 20.9 F and 27.6 M for in situ, and 55.2 F and 69.0 M for total melanoma. More in situ melanoma occurred in older patients and on the head and neck. Geometric mean Breslow thickness for invasive was 0.78 mm F and 0.85 mm M, with thicker lesions at ages over 60 and on the lower limb; there was no significant relationship with sex, distance from care or social deprivation assessed from residential address. Nodular melanomas (15%) were more frequent in older and male patients, and on the limbs, and were thicker. The estimated cumulative risk for melanoma is 4.4% F and 4.6% M by age 70. The body site distribution and sex differences were consistent with sun exposure patterns. Estimated incidence of melanoma in New Zealand in 2018 is 2500 invasive and 1700 in situ cases. Conclusions Assessing both in situ and invasive melanoma expands the clinical picture, better estimating health care demand and costs. Results suggest that in situ disease is a more slowly growing lesion than the early phase of invasive disease. The features of thicker or nodular melanoma show priorities for prevention and early detection.

A novel method for the sensory evaluation of wine and cider is proposed that combines advantages of other commonly used techniques while simplifying a tasting protocol that is more accessible for unexperienced panelists. The method is based on panelist’s evaluation of samples in three discrete and directed steps; evaluation of head, heart, and base characters. The technique provides the sensory analyst with a simplified approach to difference testing and, in many instances, helps statistically differentiate samples by reducing panelist confusion. The head aroma is defined as the first impression after removing the lid from a covered glass prior to agitating the sample. The heart aroma is defined as the primary impression after agitating the sample. The base character is defined as the final aroma impression and retronasal evaluation of the product. Each component is evaluated independently using a generalized grouping of descriptors; sensory impression or grouping descriptors can be refined if the analyst aims to draw a higher level of detail or descriptive analysis from their panel. Application of the proposed analytical protocol suggests that the technique is simple for less-experienced panelists to learn and follow, and allowed them to easily focus on the testing attributes with minimal confusion of confounding factors.

Aim: To describe the clinical features, treatment and outcomes in Australian adults with focal segmental glomerulosclerosis and identify predictors of disease progression and all-cause mortality. Methods: The study included all patients with biopsy confirmed focal segmental glomerulosclerosis between January 1997 and June 2014 at participating hospitals. Clinical factors, histopathological findings, biochemical markers and treatments were analysed and potential predictors of doubling serum creatinine, end stage kidney disease or death identified. Results: 98 patients were included with a median follow-up of 4.3 years. 34 (35%) patients were Aboriginal or Torres Strait Islander. Focal segmental glomerulosclerosis not otherwise specified was the most common variant. 17 (59%) patients initially treated with immunosuppression experienced an improvement in renal function. At the end of follow-up 43 (44%) patients had progressed to the composite outcome. Baseline tubulointerstitial scarring and lower haemoglobin predicted shorter time to doubling serum creatinine. Dual diagnosis, higher serum creatinine, lower estimated glomerular filtration rate and doubling creatinine were associated with shorter time to end stage kidney disease with remission the only protective factor. Age was the only variable associated with all-cause mortality. Conclusion: Focal segmental glomerulosclerosis holds serious implications for patients. Concomitant diabetic nephropathy, higher serum creatinine and lower estimated glomerular filtration rate at renal biopsy were associated with poorer renal prognosis. Indigenous people had a female predominance and are over-represented in relation to their population size, however were not associated with poorer prognosis. Remission was the only modifiable variable and thus should be at the forefront of patient management goals and future studies.

Background The incidence, presentation and outcomes of lupus nephritis (LN) vary with geography, ethnicity, socioeconomic status and gender. There are relatively few data on LN in the non-Caucasian populations in Australia. Aims To describe the clinical presentation, histological features, natural history, and outcomes of a historical cohort of Aboriginal and Torres Strait Islanders people in Far North Queensland with biopsy-proven LN. Methods This is a retrospective observational study, and the study was conducted in Cairns and Hinterland Hospital and Health Service, Queensland, Australia. The study included Aboriginal and Torres Strait Islander patients with biopsy-proven LN treated between 1990 and 2013. The main outcome measures were renal replacement therapy and overall patient survival. Results Aboriginal and Torres Strait Islander people represented a substantial proportion (n = 16/40, 40%) of all patients diagnosed with LN during the observation period. The frequency of nephrotic range proteinuria (n = 11/14, 78.5%), estimated glomerular filtration rate

Until a few years ago, lymphatic vessels and lymphatic endothelial cells (LEC) were viewed as part of a passive conduit for lymph and immune cells to reach lymph nodes (LN). However, recent work has shown that LEC are active immunological players whose interaction with dendritic cells and T cells is of important immunomodulatory relevance. While the immunological interaction between LEC and other immune cells has taken a center stage, molecular analysis of LEC antigen processing and presentation machinery is still lagging. Herein we review the current knowledge of LEC MHC I and MHC II antigen processing and presentation pathways, Including the role of LEC in antigen phagocytosis, classical, and non-classical MHC II presentation, proteasome processing and MHC I presentation, and cross-presentation. The ultimate goal is to provide an overview of the LEC antigen processing and presentation machinery that constitutes the molecular basis for their role in MHC I and MHC II-restricted immune responses.

Alcohol dependence has long been related to impaired emotion regulation-including reappraisal-but little is known about the performance and associated neural activity of alcohol-dependent patients (ADPs) on an emotion reappraisal task. This study, therefore, compares reappraisal of negative, positive, neutral, and alcohol-related images at a behavioral and neural level between ADPs and healthy controls (HCs). Thirty-nine ADPs and 39 age-, gender-, and education-matched HCs performed an emotion reappraisal task during functional magnetic resonance imaging (fMRI), and craving was measured before and after the reappraisal task. During the emotion reappraisal task, participants were instructed to either attend or reappraise positive, negative, neutral, or alcohol-related images, and to indicate their experienced emotion on a visual analogue scale (VAS). Both ADPs and HCs completed the emotion reappraisal task successfully, showing significant differences in self-reported experienced emotion after attending versus reappraising visual stimuli and in brain activity in emotion processing/reappraisal relevant areas. ADPs were not impaired in cognitive reappraisal at a behavioral or neural level relative to HCs, nor did ADPs indicate any difference in self-reported emotion while attending emotional images. However, ADPs were different from HC in emotion processing: ADPs revealed a blunted response in the (posterior) insula, precuneus, operculum, and superior temporal gyrus while attending emotional images compared neutral images compared to HCs, and in ADPs, higher baseline craving levels were associated with a less blunted response to alcohol-related images than in HCs. These results reveal that ADPs do not show impaired reappraisal abilities when instructed, although future studies should assess voluntary reappraisal abilities in alcohol-dependent patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02557815.

Lymphatic and blood vessels are formed by specialized lymphatic endothelial cells (LEC) and blood endothelial cells (BEC), respectively. These endothelial populations not only form peripheral tissue vessels, but also critical supporting structures in secondary lymphoid organs, particularly the lymph node (LN). Lymph node LEC (LN-LEC) also have been shown to have important immunological functions that are not observed in LEC from tissue lymphatics. LN-LEC can maintain peripheral tolerance through direct presentation of self-antigen via MHC-I, leading to CD8 T cell deletion; and through transfer of self-antigen to dendritic cells for presentation via MHC-II, resulting in CD4 T cell anergy. LN-LEC also can capture and archive foreign antigens, transferring them to dendritic cells for maintenance of memory CD8 T cells. The molecular basis for these functional elaborations in LN-LEC remain largely unexplored, and it is also unclear whether blood endothelial cells in LN (LN-BEC) might express similar enhanced immunologic functionality. Here, we used RNA-Seq to compare the transcriptomic profiles of freshly isolated murine LEC and BEC from LN with one another and with freshly isolated LEC from the periphery (diaphragm). We show that LN-LEC, LN-BEC, and diaphragm LEC (D-LEC) are transcriptionally distinct from one another, demonstrating both lineage and tissue-specific functional specializations. Surprisingly, tissue microenvironment differences in gene expression profiles were more numerous than those determined by endothelial cell lineage specification. In this regard, both LN-localized endothelial cell populations show a variety of functional elaborations that suggest how they may function as antigen presenting cells, and also point to as yet unexplored roles in both positive and negative regulation of innate and adaptive immune responses. The present work has defined in depth gene expression differences that point to functional specializations of endothelial cell populations in different anatomical locations, but especially the LN. Beyond the analyses provided here, these data are a resource for future work to uncover mechanisms of endothelial cell functionality.

The North Atlantic Ocean and adjacent shelf seas play a crucial role in global climate. To better constrain long-term natural variability and marine-terrestrial linkages in this region, a network of highly resolved marine archives from the open ocean and continental shelves is needed. In recent decades, bivalve sclerochronology has emerged as a field providing such records from the mid- to high latitudes. In May 2014, dead valves and young live specimens of the bivalve Glycymeris glycymeris were collected at St Kilda, Scotland. A floating chronology spanning 187 years was constructed with fossil shells and radiocarbon dated to 3910–3340 cal yr before present (BP), with a probability density cluster at ca. 3700–3500 cal yr BP. Sub-annual δ18O data were obtained from five fossil and three modern specimens and showed a strong seasonal signal in both time intervals. The growth season of G. glycymeris at this location today lasts from May to October, with most growth occurring before the temperature peak in August. Thus, the modern specimens and the fossil chronology represent late-spring and summer sea surface temperatures (SST). The annual temperature range was 4.4 °C in the fossil shells, which is similar to the range observed today (3.8 °C). Average SSTs reconstructed from the fossil shells were 1 °C cooler than in 2003–2013 CE and similar to the early 20th century CE. The radiocarbon age of the floating chronology coincides with a climatic shift to wetter conditions on the British Isles and with a cold interval observed in palaeoceanographic records from south of Iceland. However, our data do not provide evidence of a cold interval on the Scottish shelf. The similarity in growth season and temperature range between the fossil and modern specimens are attributed to similar boundary conditions in the fourth millennium BP compared to today.

Adhesive shoulder capsulitis, or arthrofibrosis, describes a pathological process in which the body forms excessive scar tissue or adhesions across the glenohumeral joint, leading to pain, stiffness and dysfunction. It is a debilitating condition that can occur spontaneously (primary or idiopathic adhesive capsulitis) or following shoulder surgery or trauma (secondary adhesive capsulitis). Here, we review the pathophysiology of adhesive shoulder capsulitis, highlighting its clinical presentation, natural history, risk factors, pathoanatomy and pathogenesis. Both current non-operative and operative treatments for adhesive capsulitis are described, and evidence-based studies are presented in support for or against each corresponding treatment. Finally, the review also provides an update on the gene expression profile of adhesive capsulitis and how this new understanding can help facilitate development of novel pharmacological therapies.

While evaluation, diagnosis, and treatment of soft tissue masses are a daily part of the orthopaedic oncologist's practice, it is rare for a patient to present initially to the orthopaedic clinic with melanoma. More commonly, the patient presents as a referral from the medical oncologist for 1) evaluation of a long bone metastasis concerning for [impending] pathologic fracture or 2) amputation of a digit or limb to achieve wide resection for cure. We present here a rare case of metastatic melanoma presenting initially to the orthopaedic oncologist as a fungating soft tissue mass concerning for a sarcoma. Through effective collaboration with a melanoma specialist at our cancer center, an impressive local response was observed within weeks of initiating targeted therapy with encorafenib and binimetinib. The patient was thus spared a palliative amputation.

Background: The role of chronotype, the individual timing of sleep/activity, has been studied in relation todepressive and anxiety disorders. A cross-sectional association between a depressive episode and evening-typehas been identified. However, until now the predicting capacity of chronotype concerning persistence of psy-chiatric disorders remains unclear. Our aim is to examine whether a later chronotype in patients with a de-pressive and/or anxiety disorder can serve as a predictor of a persistent course.Methods: A subsample of patients with a depressive and/or anxiety disorder diagnosis and chronotype data ofthe longitudinal Netherlands Study of Depression and Anxiety (NESDA) was used. Diagnosis of depressive andanxiety disorders (1-month DSM-IV based diagnosis) were determined at baseline (n = 505). From this grouppersistence was determined at 2-year (FU2) (persistent course: n = 248, non-persistent course: n = 208) and 4-year follow-up (FU4) (persistent course: n = 151, non-persistent course: n = 264). Chronotype was assessed atbaseline with the Munich Chronotype Questionnaire.Results: A later chronotype did not predict a persistent course of depressive and/or anxiety disorder at FU2 (OR(95% CI) = 0.99 (0.83–1.19), P = 0.92) or at FU4 (OR (95% CI) = 0.94 (0.77–1.15), P = 0.57).Limitations: Persistence was defined as having a diagnosis of depressive and/or anxiety disorder at the two-yearand four-year follow-up, patients may have remitted and relapsed between assessments.Conclusion: Chronotype, measured as actual sleep timing, of patients with a depressive or anxiety disorder didnot predict a persistent course which suggests it might be unsuitable as predictive tool in clinical settings.

Supplemental material, DS_10.1177_2381468318808503 for Designing Shared Decision-Making Interventions for Dissemination and Sustainment: Can Implementation Science Help Translate Shared Decision Making Into Routine Practice? by Andy S. L. Tan, Kathleen M. Mazor, Daniel McDonald, Stella J. Lee, Demetria McNeal, Daniel D. Matlock and Russell E. Glasgow in MDM Policy & Practice

In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.

Motor axons in peripheral nerves have the capacity to regenerate after injury. However, full functional motor recovery rarely occurs clinically, and this depends on the nature and location of the injury. Recent preclinical findings suggest that there may be a time after nerve injury where, while regrowth to the muscle successfully occurs, there is nevertheless a failure to re-establish motor function, suggesting a possible critical period for synapse reformation. We have now examined the temporal and anatomical determinants for the re-establishment of motor function after prolonged neuromuscular junction (NMJ) denervation in rats and mice. Using both sciatic transection-resuture and multiple nerve crush models in rats and mice to produce prolonged delays in reinnervation, we show that regenerating fibres reach motor endplates and anatomically fully reform the NMJ even after extended periods of denervation. However, in spite of this remarkably successful anatomical regeneration, after 1 month of denervation there is a consistent failure to re-establish functional recovery, as assessed by behavioural and electrophysiological assays. We conclude that this represents a failure in re-establishment of synaptic function, and the possible mechanisms responsible are discussed, as are their clinical implications.

BACKGROUND: Recent studies have shown that response inhibition is impaired in patients with obsessive-compulsive disorder and their unaffected siblings, suggesting that these deficits may be considered a cognitive endophenotype of obsessive-compulsive disorder. Structural and functional neural correlates of altered response inhibition have been identified in patients and siblings. This study aims to examine the functional integrity of the response inhibition network in patients with obsessive-compulsive disorder and their unaffected siblings. METHODS: Forty-one unmedicated patients with obsessive-compulsive disorder, 17 of their unaffected siblings and 37 healthy controls performed a stop signal task during functional magnetic resonance imaging. Psycho-physiological interaction analysis was used to examine functional connectivity between the following regions of interest: the bilateral inferior frontal gyri, presupplementary motor area, subthalamic nuclei, inferior parietal lobes, anterior cingulate cortex, and amygdala. We then used dynamic causal modeling to investigate the directionality of the networks involved. RESULTS: Patients, and to a lesser extent also their unaffected siblings, show altered connectivity between the inferior frontal gyrus and the amygdala during response inhibition. The follow-up dynamic causal modeling suggests a bottom-up influence of the amygdala on the inferior frontal gyrus in healthy controls, whereas processing occurs top-down in patients with obsessive-compulsive, and in both directions in siblings. CONCLUSIONS: Our findings suggest that amygdala activation in obsessive-compulsive disorder interferes differently with the task-related recruitment of the inhibition network, underscoring the role of limbic disturbances in cognitive dysfunctions in obsessive-compulsive disorder. Hum Brain Mapp 36:4064-4075, 2015. © 2015 Wiley Periodicals, Inc.

© 2015 Elsevier Inc. Axon regeneration in the CNS requires reactivating injured neurons' intrinsic growth state and enabling growth in an inhibitory environment. Using an inbred mouse neuronal phenotypic screen, we find that CAST/Ei mouse adult dorsal root ganglion neurons extend axons more on CNS myelin than the other eight strains tested, especially when pre-injured. Injury-primed CAST/Ei neurons also regenerate markedly in the spinal cord and optic nerve more than those from C57BL/6 mice and show greater sprouting following ischemic stroke. Heritability estimates indicate that extended growth in CAST/Ei neurons on myelin is genetically determined, and two whole-genome expression screens yield the Activin transcript Inhba as most correlated with this ability. Inhibition of Activin signaling in CAST/Ei mice diminishes their CNS regenerative capacity, whereas its activation in C57BL/6 animals boosts regeneration. This screen demonstrates that mammalian CNS regeneration can occur and reveals a molecular pathway that contributes to this ability. Omura et al. screened for neuronal growth on myelin and find CAST/Ei inbred mice are uniquely able to regenerate axons in the injured CNS through Activin signaling. Enhancing Activin signaling confers a CNS-regenerative capacity in normally non-regenerative mouse strains.

Objective: Case‐control studies have linked mobile phone use to an increased risk of glioma in the most exposed brain areas, the temporal and parietal lobes, although inconsistently. We examined time trends in the incidence rates of brain malignancies in New Zealand from 1995 to 2010. Methods: Data from the New Zealand Cancer Registry was used to calculate incidence rates of primary brain cancer, by age, gender, morphology and anatomical site. Log‐linear regression analysis was used to assess trends in the annual incidence of primary brain cancer; annual percentage changes and their 95% confidence intervals were estimated. Results: No consistent increases in all primary brain cancer, glioma, or temporal or parietal lobe glioma were seen. At ages 10–69, the incidence of all brain cancers declined significantly. Incidence of glioma increased at ages over 70. Conclusion: In New Zealand, there has been no consistent increase in incidence rates of primary brain cancers. An increase in glioma at ages over 70 is likely to be due to improvements in diagnosis. As with any such studies, a small effect, or one with a latent period of more than 10 to 15 years, cannot be excluded.

The lymphatic endothelium (LE) serves as a conduit for transport of immune cells and soluble antigens from peripheral tissues to draining lymph nodes (LNs), contributing to development of host immune responses and possibly dissemination of microbes. Lymphatic endothelial cells (LECs) are major constituents of the lymphatic endothelium. These specialized cells could play important roles in initiation of host innate immune responses through sensing of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs), including toll-like receptors (TLRs). LECs secrete pro-inflammatory cytokines and chemokines to create local inflammatory conditions for recruitment of naive antigen presenting cells (APCs) such as dendritic cells (DCs) to sites of infection and/or vaccine administration. In this study, we examined the innate immune potential of primary LEC populations derived from multiple tissues of an animal model for human infectious diseases – the ferret. We generated a total of six primary LEC populations from lung, tracheal, and mesenteric LN tissues from three different ferrets. Standard RT-PCR characterization of these primary LECs showed that they varied in their expression of LEC markers. The ferret LECs were examined for their ability to respond to poly I:C (TLR3 and RIG-I ligand) and other known TLR ligands as measured by production of proinflammatory cytokine (IFNα, IL6, IL10, Mx1, and TNFα) and chemokine (CCL5, CCL20, and CXCL10) mRNAs using real time RT-PCR. Poly I:C exposure induced robust proinflammatory responses by all of the primary ferret LECs. Chemotaxis was performed to determine the functional activity of CCL20 produced by the primary lung LECs and showed that the LEC-derived CCL20 was abundant and functional. Taken together, our results continue to reveal the innate immune potential of primary LECs during pathogen-host interactions and expand our understanding of the roles LECs might play in health and disease in animal models.

Objectives: Impaired response inhibition is related to neurodevelopmental disorders, such as Tourette’s disorder (TD) and obsessive-compulsive disorder (OCD). Unlike OCD, in which neural correlates of response inhibition have been extensively studied, TD literature is limited. By using a Stop-Signal task, we investigated the neural mechanisms underlying response inhibition deficits in TD compared to OCD and healthy controls (HCs). Methods: Twenty-three TD patients, 20 OCD patients and 22 HCs were scanned (3T MRI). Region-of-interest analyses were performed between TD, OCD and HCs. Results: Performance was similar across all subject groups. During inhibition TD compared with HCs showed higher right inferior parietal cortex (IPC) activation. During error processing TD compared with HCs showed hyperactivity in the left cerebellum, right mesencephalon, and right insula. Three-group comparison showed an effect of group for error-related activation in the supplementary motor area (SMA). Post-hoc analyses showed higher error-related SMA activity in TD compared with OCD and HCs. Error-related left cerebellar activity correlated positively with tic severity. Conclusions: Hyperactivation of IPC during inhibition and a widespread hyperactivated network during error processing in TD suggest compensatory inhibition- and error-related circuit recruitment to boost task performance. The lack of overlap with activation pattern in OCD suggests such compensatory mechanism is TD-specific.