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Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

BACKGROUND: Shearer et al in 2014 articulated well-defined criteria for the diagnosis and classification of severe combined immunodeficiency (SCID) as part of the Primary Immune Deficiency Treatment Consortiums (PIDTCs) prospective and retrospective studies of SCID. OBJECTIVE: Because of the advent of newborn screening for SCID and expanded availability of genetic sequencing, revision of the PIDTC 2014 Criteria was needed. METHODS: We developed and tested updated PIDTC 2022 SCID Definitions by analyzing 379 patients proposed for prospective enrollment into Protocol 6901, focusing on the ability to distinguish patients with various SCID subtypes. RESULTS: According to PIDTC 2022 Definitions, 18 of 353 patients eligible per 2014 Criteria were considered not to have SCID, whereas 11 of 26 patients ineligible per 2014 Criteria were determined to have SCID. Of note, very low numbers of autologous T cells (

BackgroundThe DNA-repair enzyme Artemis is essential for rearrangement of T- and B-cell receptors. Mutations in DCLRE1C, which encodes Artemis, cause Artemis-deficient severe combined immunodeficiency (ART-SCID), which is poorly responsive to allogeneic hematopoietic-cell transplantation.MethodsWe carried out a phase 1-2 clinical study of the transfusion of autologous CD34+ cells, transfected with a lentiviral vector containing DCLRE1C, in 10 infants with newly diagnosed ART-SCID. We followed them for a median of 31.2 months.ResultsMarrow harvest, busulfan conditioning, and lentiviral-transduced CD34+ cell infusion produced the expected grade 3 or 4 adverse events. All the procedures met prespecified criteria for feasibility at 42 days after infusion. Gene-marked T cells were detected at 6 to 16 weeks after infusion in all the patients. Five of 6 patients who were followed for at least 24 months had T-cell immune reconstitution at a median of 12 months. The diversity of T-cell receptor β chains normalized by 6 to 12 months. Four patients who were followed for at least 24 months had sufficient B-cell numbers, IgM concentration, or IgM isohemagglutinin titers to permit discontinuation of IgG infusions. Three of these 4 patients had normal immunization responses, and the fourth has started immunizations. Vector insertion sites showed no evidence of clonal expansion. One patient who presented with cytomegalovirus infection received a second infusion of gene-corrected cells to achieve T-cell immunity sufficient for viral clearance. Autoimmune hemolytic anemia developed in 4 patients 4 to 11 months after infusion; this condition resolved after reconstitution of T-cell immunity. All 10 patients were healthy at the time of this report.ConclusionsInfusion of lentiviral gene-corrected autologous CD34+ cells, preceded by pharmacologically targeted low-exposure busulfan, in infants with newly diagnosed ART-SCID resulted in genetically corrected and functional T and B cells. (Funded by the California Institute for Regenerative Medicine and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03538899.).

Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

PurposeThe Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study's objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention.MethodsWe analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management.ResultsInfections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p = 0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p = 0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented.ConclusionInfants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS.Trial registrationNCT01186913.

The original version of this article unfortunately contained the missing author, Caridad Martinez. The authors would like to correct the list. We apologize for any inconvenience that this may have caused. The correct author list is shown above.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

Little is known about the early history of the chicken (Gallus gallus domesticus), including the timing and circumstances of its introduction into new cultural environments. To evaluate its spatio-temporal spread across Eurasia and north-west Africa, the authors radiocarbon dated 23 chicken bones from presumed early contexts. Three-quarters returned dates later than those suggested by stratigraphy, indicating the importance of direct dating. The results indicate that chickens did not arrive in Europe until the first millennium BC. Moreover, a consistent time-lag between the introduction of chickens and their consumption by humans suggests that these animals were initially regarded as exotica and only several centuries later recognised as a source of 'food'. Keywords: Europe, north-west Africa, chickens, AMS dating, dispersal, domestication, Introduction The chicken (Galiusgallus domesticus) is the most widely distributed domestic animal on the planet (Nicol 2015). Transported around the world by people, the species is now established across a [...]

IntroductionInflammatory bowel disease (IBD) affects approximately 1/3 of patients with chronic granulomatous disease (CGD). Comprehensive investigation of the effect of allogeneic hematopoietic cell transplantation (HCT) on CGD IBD and the impact of IBD on transplant outcomes is lacking.MethodsWe collected data retrospectively from 145 patients with CGD who had received allogeneic HCT at 26 Primary Immune Deficiency Treatment Consortium (PIDTC) centers between January 1, 2005 and June 30, 2016.ResultsForty-nine CGD patients with IBD and 96 patients without IBD underwent allogeneic HCT. Eighty-nine percent of patients with IBD and 93% of patients without IBD engrafted (p = 0.476). Upper gastrointestinal acute GVHD occurred in 8.5% of patients with IBD and 3.5% of patients without IBD (p = 0.246). Lower gastrointestinal acute GVHD occurred in 10.6% of patients with IBD and 11.8% of patients without IBD (p = 0.845). The cumulative incidence of acute GVHD grades II-IV was 30% (CI 17-43%) in patients with IBD and 20% (CI 12-29%) in patients without IBD (p = 0.09). Five-year overall survival was equivalent for patients with and without IBD: 80% [CI 66-89%] and 83% [CI 72-90%], respectively (p = 0.689). All 33 surviving evaluable patients with a history of IBD experienced resolution of IBD by 2 years following allogeneic HCT.ConclusionsIn this cohort, allogeneic HCT was curative for CGD-associated IBD. IBD should not contraindicate HCT, as it does not lead to an increased risk of mortality. This study is registered at clinicaltrials.gov NCT02082353.

The few existing typology studies on women who have sexually offended (WWSO) have largely been limited by small sample sizes, have not included scale scores from risk assessments, or used recidivism within their typology (instead of using typologies to predict recidivism). In our sample of 241 WWSO, we conducted a latent profile analysis and observed four, distinct profiles: "low-risk WWSO," characterized by fewer criminal history incidents and lower risk-assessment scores; "problem-endorsing WWSO," with higher probability of endorsing various life problems such as educational/employment and emotional/personal issues; "antisocial WWSO" with more criminal history incidents, alcohol/drug problems, and higher scores on psychopathy; and "combined WWSO" with characteristics of both the problem-endorsing and antisocial profiles. This last profile showed elevations in general and/or violent recidivism risk, but relatively low recidivism. There were no cases of sexual recidivism in our sample following an average 30-month follow-up period. Membership in the antisocial profile predicted general and/or violent recidivism and suggests that WWSO typologies may be useful in predicting non-sexual recidivism for this population. [ABSTRACT FROM AUTHOR]

Although most risk assessment research has examined tools in the prediction of recidivism, there is a growing body of literature that investigates risk assessment in the prediction of successful community supervision. The Texas Risk Assessment System–Community Supervision Tool (TRAS-CST) was developed from the Ohio Risk Assessment System–Community Supervision Tool (ORAS-CST) but has not been examined to predict recidivism or probation compliance. The current study investigates the predictive validity of the TRAS screener and full versions when examining supervision compliance and recidivism among a sample of 462 individuals on probation. Findings support predictive validity of incarceration due to rule violations and new offenses during supervision using the TRAS versions, along with the domains of the TRAS-CST version, although the effect sizes were small to moderate. Results also indicate that the domain scores on the full TRAS may provide important intervention focus for officers supervising individuals on community supervision. [ABSTRACT FROM AUTHOR]

Prior research, using two- and three-dimensional environments, has found that when both human and nonhuman animals independently acquire two associations between landmarks with a common landmark (e.g., LM1-LM2 and LM2-LM3), each with its own spatial relationship, they behave as if the two unique LMs have a known spatial relationship despite their never having been paired. Seemingly, they have integrated the two associations to create a third association with its own spatial relationship (LM1-LM3). Using sensory preconditioning (Experiment 1) and second-order conditioning (Experiment 2) procedures, we found that human participants integrated information about the boundaries of pathways to locate a goal within a three-dimensional virtual environment in the absence of any relevant landmarks. Spatial integration depended on the participant experiencing a common boundary feature with which to link the pathways. These results suggest that the principles of associative learning also apply to the boundaries of an environment.

The central executive is theorized to be an overarching cognitive system responsible for coordinatingprocesses that enable self-control (i.e., inhibiting habitual responses), persistence at mental andphysical tasks, emotional regulation and working memory (Gailliot, 2008; Miller & Cohen, 2001).There is evidence that the executive system relies on glucose as its energy resource (Gailliot et al.,2007) and that when humans invoke the central executive they expend large quantities of glucose.When glucose levels are low, humans perform more poorly on other tasks that rely on the central executive (Gailliot et al., 2007). Similar results have been obtained with non-human animals. When dogs are required to exert self-control on an initial task they persist for a shorter duration at asubsequent unrewarding task and are more impulsive than if they were not required to exert selfcontrol(Miller, DeWall, Pattison, Molet, & Zentall, in press; Miller, Pattison, Rayburn-Reeves,DeWall, & Zentall, 2010). Given the similarities between human and non-human animals, further research on executive control processing and glucose depletion with non-human animals is encouraged. Such research may lead to interventions that sustain and replenish executive control.

Despite research showing that many college men and women have experienced misperception of their friendliness as sexual intent, such research has focused on this type of misperception only as a correlate of men's sexual aggression. In fact, regardless of methodology used many researchers seem to suggest women do not misperceive men's sexual intent, and in some instances may actually under-perceive it. We used a hypothetical scenario to determine whether men (n = 324) and women (n = 689) college students perceived similar sexual intent from a character who is not the same gender as they are, as depicted in a story about a man and woman on a "date." Our results revealed that men and women in our sample reported similar levels of perceived sexual intent on the part of the character with a different gender as described in the scenario, even after that character clearly indicated to the partner that they "think they do not want to have sex." In addition, the perceived level of the character's sexual intent as solicited in response to this scenario design was related to sexual coercion intentions among both men and women (though it appears more strongly related among men), and these relationships remained even after controlling for other known correlates of sexual coercion (e.g., rape myth acceptance, level of sexual arousal). Implications for the study of misperception and its origins are discussed. [ABSTRACT FROM AUTHOR]

Traditional microbiology laboratory activities tend to focus solely on skill development, leaving untapped the great potential for students' deep understanding of underlying fundamental microbiology concepts. To address this issue, I present an inquiry-based instructional sequence for a common skill-based lab in undergraduate majors' and non-majors' biology: the Gram stain. The modified lab includes elements of inquiry without completely overhauling the original activity to allow for both skill-based and conceptual knowledge development. With a few alterations, this instructional sequence could easily be tailored to suit similar microbiology labs. This instructional sequence could also be used to modify biology labs into inquiry lessons at any grade level. [ABSTRACT FROM AUTHOR]

The increase in youth and adult use of pornography has led to increased research on the possible effects and implications of such use. A few prior studies have examined the relationship between age at first exposure to pornography and related problems later in life, including more problematic use of pornography. The current study used a sample of 924 males and females at a university in the Southern United States to examine the relationship between age and type of first pornography exposure to problematic use of pornography in young adulthood. Results indicated significant relationships between age at first exposure, first exposure type, and problematic pornography use in young adulthood. The findings highlight the importance of early intervention around pornography exposure and the causes of intentional pornography use at early ages. [ABSTRACT FROM AUTHOR]

Researchers have found that both women and men engage in verbal and physical sexually coercive behaviours (Black et al. [2011]. The National Intimate Partner and Sexual Violence Survey (NISVS): 2010 summary report. National Center for Injury Prevention and Control, Centers for Disease Control and Prevention; Bouffard et al. [2016]. Examining the correlates of women's use of sexual coercion: Proposing an explanatory model. Journal of Interpersonal Violence, 31(13), 2360–2382. ). Risk factors such as rape myth acceptance and prior victimisation related to sexual coercion have been identified however, no research has examined how potential protective factors may impact engaging in this kind of behaviour. The current study examined how risk and protective factors related to the incidence of sexual coercion among a sample of 713 college women from a southern university. The results of the study supported previous findings on risk factors such as higher rape myth acceptance, having experienced prior sexual victimisation, and having a lower belief in the law, were significantly related to engaging in sexual coercion for the women in this sample. Findings indicated several protective factors were significantly related to lower chances of having engaged in sexual coercion, such as increased ability to control thoughts and behaviour and having positive social support. The significance of these findings and implications are discussed. Practice impact statement: This article can assist educators and professionals with developing sexual assault prevention programmes by explaining what factors are significant to college-aged women's willingness to engage in coercive behaviour. [ABSTRACT FROM AUTHOR]

Over the last 10,000 y, humans have manipulated fallow deer populations with varying outcomes. Persian fallow deer (Dama mesopotamica) are now endangered. European fallow deer (Dama dama) are globally widespread and are simultaneously considered wild, domestic, endangered, invasive and are even the national animal of Barbuda and Antigua. Despite their close association with people, there is no consensus regarding their natural ranges or the timing and circumstances of their human-mediated translocations and extirpations. Our mitochondrial analyses of modern and archaeological specimens revealed two distinct clades of European fallow deer present in Anatolia and the Balkans. Zooarchaeological evidence suggests these regions were their sole glacial refugia. By combining biomolecular analyses with archaeological and textual evidence, we chart the declining distribution of Persian fallow deer and demonstrate that humans repeatedly translocated European fallow deer, sourced from the most geographically distant populations. Deer taken to Neolithic Chios and Rhodes derived not from nearby Anatolia, but from the Balkans. Though fallow deer were translocated throughout the Mediterranean as part of their association with the Greco-Roman goddesses Artemis and Diana, deer taken to Roman Mallorca were not locally available Dama dama, but Dama mesopotamica. Romans also initially introduced fallow deer to Northern Europe but the species became extinct and was reintroduced in the medieval period, this time from Anatolia. European colonial powers then transported deer populations across the globe. The biocultural histories of fallow deer challenge preconceptions about the divisions between wild and domestic species and provide information that should underpin modern management strategies. [ABSTRACT FROM AUTHOR]

Research on pornography use and sexual coercion has provided inconsistent results. One explanation for this is the lack of a valid, reliable, and comprehensive measure of pornography use. This study seeks to address this need by developing a comprehensive pornography use instrument consisting of four domains identified in research: type of pornography used, sexual scripts, habits, and compulsivity. A sample of 324 college men was used. Results of the study yielded factor structures for these domains and evidence of reliability and validity. Findings present the initial development of a pornography use instrument that could improve research in this area and aid practitioners in treatment and supervision decisions. [ABSTRACT FROM AUTHOR]

The current study explores the relationship between psychopathy, cognitive distortions that could promote sexual coercion, i.e., rape myth acceptance (RMA) and misperception of sexual intent (MPSI), and one's level of sexual arousal on the intentions to use sexual coercion. Using a sample of 218 college men (aged 18–69) and a hypothetical vignette design, we examine potential direct and indirect effects of psychopathy on coercion intentions. Psychopathy directly related to coercion intentions and also operated indirectly through RMA. Furthermore, RMA was related to coercion intentions through MPSI. Implications for understanding sexual coercion pathways and prevention efforts are discussed. [ABSTRACT FROM AUTHOR]