Three novel Er blood group system alleles and insights from protein modeling.

BACKGROUND: The Er blood group system was recently shown to be defined by PIEZO1. The system consists of high prevalence antigens Era, Er3, ERSA, and ERAMA; and low prevalence antigen Erb. Era/Erb are antithetical with Er(a-b+) defined by the ER*B allele [c.7180G>A p.(Gly2394Ser)]. A nonsense variant c.5289C>G p.(Tyr1763*) is associated with a predicted Ernull phenotype, and a missense variant c.7174G>A p.(Glu2392Lys) in close proximity to p.2394 causes loss of both Era and Erb expression. STUDY DESIGN AND METHODS: We investigated PIEZO1 in four Er(a-) individuals who presented with anti-Era. Whole genome sequencing (WGS) and Sanger sequencing were performed. The location and structural differences of predicted protein changes were visualized using the predicted 3-D structure of Piezo1 created using AlphaFold2. RESULTS: One individual was homozygous for the reported ER*B. A second had a novel heterozygous nonsense variant c.3331C>T p.(Gln1111*), but a second allelic variant was not found. In the remaining two individuals, two different heterozygous novel missense variants, c.7184C>T p.(Ala2395Val) or c.7195G>A p.(Gly2399Ser), were in trans to the reported c.7180G>A variant, ER*B. AlphaFold2 protein modeling showed that each of the missense variants is predicted to encode an altered structural conformation near Era and Erb. CONCLUSIONS: Investigation of archived samples resulted in the identification of three novel PIEZO1 alleles including a predicted Ernull and two missense variants. Structural modeling suggests that the missense changes potentially alter Era/Erb epitope expression with p.2399Ser resulting in a small increase in the negative electrostatic potential.

ABO Genotyping finds more A2 to B kidney transplant opportunities than lectin-based subtyping.

ABO compatibility is important for kidney transplantation, with longer waitlist times for blood group B kidney transplant candidates. However, kidneys from non-A1 (eg, A2) subtype donors, which express less A antigen, can be safely transplanted into group B recipients. ABO subtyping is routinely performed using anti-A1 lectin, but DNA-based genotyping is also possible. Here, we compare lectin and genotyping testing. Lectin and genotype subtyping was performed on 554 group A deceased donor samples at 2 transplant laboratories. The findings were supported by 2 additional data sets of 210 group A living kidney donors and 124 samples with unclear lectin testing sent to a reference laboratory. In deceased donors, genotyping found 65% more A2 donors than lectin testing, most with weak lectin reactivity, a finding supported in living donors and samples sent for reference testing. DNA sequencing and flow cytometry showed that the discordances were because of several factors, including transfusion, small variability in A antigen levels, and rare ABO∗A2.06 and ABO∗A2.16 sequences. Although lectin testing is the current standard for transplantation subtyping, genotyping is accurate and could increase A2 kidney transplant opportunities for group B candidates, a difference that should reduce group B wait times and improve transplant equity.

Multiple GYPB gene deletions associated with the U- phenotype in those of African ancestry.

BACKGROUND: The MNS blood group system is defined by three homologous genes: GYPA, GYPB, and GYPE. GYPB encodes for glycophorin B (GPB) carrying S/s and the "universal" antigen U. RBCs of approximately 1% of individuals of African ancestry are U- due to absence of GPB. The U- phenotype has long been attributed to a deletion encompassing GYPB exons 2 to 5 and GYPE exon 1 (GYPB*01N). STUDY DESIGN AND METHODS: Samples from two U-individuals underwent Illumina short read whole genome sequencing (WGS) and Nanopore long read WGS. In addition, two existing WGS datasets, MedSeq (n = 110) and 1000 Genomes (1000G, n = 2535), were analyzed for GYPB deletions. Deletions were confirmed by Sanger sequencing. Twenty known U- donor samples were tested by a PCR assay to determine the specific deletion alleles present in African Americans. RESULTS: Two large GYPB deletions in U- samples of African ancestry were identified: a 110 kb deletion extending left of GYPB (DEL_B_LEFT) and a 103 kb deletion extending right (DEL_B_RIGHT). DEL_B_LEFT and DEL_B_RIGHT were the most common GYPB deletions in the 1000 Genomes Project 669 African genomes (allele frequencies 0.04 and 0.02). Seven additional deletions involving GYPB were seen in African, Admixed American, and South Asian samples. No samples analyzed had GYPB*01N. CONCLUSIONS: The U- phenotype in those of African ancestry is primarily associated with two different complete deletions of GYPB (with intact GYPE). Seven additional less common GYPB deletion backgrounds were found. GYPB*01N, long assumed to be the allele commonly encoding U- phenotypes, appears to be rare.

Overcoming the challenges of interpreting complex and uncommon RH alleles from whole genomes.

BACKGROUND AND OBJECTIVES: Rh is one of the most diverse and complex blood group systems. Recently, next generation sequencing (NGS) has proven to be a viable option for RH genotyping. We have developed automated software (bloodTyper) for determining alleles encoding RBC antigens from NGS-based whole genome sequencing (WGS). The bloodTyper algorithm has not yet been optimized and evaluated for complex and uncommon RH alleles. MATERIALS AND METHODS: Twenty-two samples with previous polymerase chain reaction (PCR) and Sanger sequencing-based RH genotyping underwent WGS. bloodTyper was used to detect RH alleles including those defined by structural variation (SV) using a combination of three independent strategies: sequence read depth of coverage, split reads and paired reads. RESULTS: bloodTyper was programmed to identify D negative and positive phenotypes as well as the presence of alleles encoding weak D, partial D and variant RHCE. Sequence read depth of coverage calculation accurately determined RHD zygosity and detected the presence of RHD/RHCE hybrids. RHCE*C was determined by sequence read depth of coverage and by split read methods. RHD hybrid alleles and RHCE*C were confirmed by using a paired read approach. Small SVs present in RHCE*CeRN and RHCE*ceHAR were detected by a combined read depth of coverage and paired read approach. CONCLUSIONS: The combination of several different interpretive approaches allowed for automated software based-RH genotyping of WGS data including RHD zygosity and complex compound RHD and RHCE heterozygotes. The scalable nature of this automated analysis will enable RH genotyping in large genomic sequencing projects.

A whole genome approach for discovering the genetic basis of blood group antigens: independent confirmation for P1 and Xga.

BACKGROUND: Although P1 and Xga are known to be associated with the A4GALT and XG genes, respectively, the genetic basis of antigen expression has been elusive. Recent reports link both P1 and Xga expression with nucleotide changes in the promotor regions and with antigen-negative phenotypes due to disruption of transcription factor binding. STUDY DESIGN AND METHODS: Whole genome sequencing was performed on 113 individuals as part of the MedSeq Project with serologic RBC antigen typing for P1 (n = 77) and Xga (n = 15). Genomic data were analyzed by two approaches, nucleotide frequency correlation and serologic correlation, to find A4GALT and XG changes associated with P1 and Xga expression. RESULTS: For P1, the frequency approach identified 29 possible associated nucleotide changes, and the serologic approach revealed four among them correlating with the P1+/P1- phenotype: chr22:43,115,523_43,115,520AAAG/delAAAG (rs66781836); chr 22:43,114,551C/T (rs8138197); chr22:43,114,020 T/G (rs2143918); and chr22:43,113,793G/T (rs5751348). For Xga , the frequency approach identified 82 possible associated nucleotide changes, and among these the serologic approach revealed one correlating with the Xg(a+)/Xg(a-) phenotype: chrX:2,666,384G/C (rs311103). CONCLUSION: A bioinformatics analysis pipeline was created to identify genetic changes responsible for RBC antigen expression. This study, in progress before the recently published reports, independently confirms the basis for P1 and Xga . Although this enabled molecular typing of these antigens, the Y chromosome PAR1 region interfered with Xga typing in males. This approach could be used to identify and confirm the genetic basis of antigens, potentially replacing the historical approach using family pedigrees as genomic sequencing becomes commonplace.

Automated typing of red blood cell and platelet antigens from whole exome sequences.

BACKGROUND: Genotyping has expanded the number red blood cell (RBC) and platelet (PLT) antigens that can readily be typed, but often represents an additional testing cost. The analysis of existing genomic data offers a cost-effective approach. We recently developed automated software (bloodTyper) for determination of RBC and PLT antigens from whole genome sequencing. Here we extend the algorithm to whole exome sequencing (WES). STUDY DESIGN AND METHODS: Whole exome sequencing was performed on samples from 75 individuals. WES-based bloodTyper RBC and PLT typing was compared to conventional polymerase chain reaction (PCR) RHD zygosity testing and serologic and single-nucleotide polymorphism (SNP) typing for 38 RBC antigens in 12 systems (17 serologic and 35 SNPs) and 22 PLT antigens (22 SNPs). Samples from the first 20 individuals were used to modify bloodTyper to interpret WES followed by blinded typing of 55 samples. RESULTS: Over the first 20 samples, discordances were noted for C, M, and N antigens, which were due to WES-specific biases. After modification, bloodTyper was 100% accurate on blinded evaluation of the last 55 samples and outperformed both serologic (99.67% accurate) and SNP typing (99.97% accurate) reflected by two Fyb and one N serologic typing errors and one undetected SNP encoding a Jknull phenotype. RHD zygosity testing by bloodTyper was 100% concordant with a combination of hybrid Rhesus box PCR and PCR-restriction fragment length polymorphism for all samples. CONCLUSION: The automated bloodTyper software was modified for WES biases to allow for accurate RBC and PLT antigen typing. Such analysis could become a routing part of future WES efforts.

Underutilization of the current clinical capacity to provide buprenorphine treatment for opioid use disorders within the Veterans Health Administration.

BACKGROUND: Opioid use disorder (OUD) is a critical concern among US veterans. The Veterans Health Administration (VHA) recommends buprenorphine as a first-line treatment for OUD; however, only 35% of veterans with an OUD currently receive medication treatment. Practical barriers, including the capacity of providers to prescribe, may affect delivery of buprenorphine. We examined the current state of buprenorphine treatment within the VHA. METHODS: National VHA administrative databases were queried to identify all providers credentialed to prescribe buprenorphine as of January 2018. Data were extracted on providers' prescribing capacity (30, 100, or 275 patients concurrently) and number of patients who received buprenorphine in the prior 180 days. RESULTS: A total of 1458 VHA providers were credentialed to prescribe buprenorphine. Forty-three percent of providers had not prescribed buprenorphine to any VHA patients in the past 180 days. Of those that prescribed to at least 1 patient, providers still prescribed to fewer patients than their capacity, regardless of their patient panel size (30, 100, or 275), prescribing to 18.5 patients on average. CONCLUSIONS: VHA providers are prescribing buprenorphine below their capacity. A multipronged approach to increase the number of credentialed providers and address barriers to prescribing is needed to ensure that veterans get effective treatment for OUD.

What changes when? The course of improvement during a stage-based treatment for suicidal and self-injuring women with borderline personality disorder and PTSD.

OBJECTIVE: Dialectical Behavior Therapy (DBT) with the DBT Prolonged Exposure (DBT PE) protocol is an integrated treatment for suicidal and self-injuring individuals with PTSD and borderline personality disorder (BPD) that occurs in three stages: Stage 1 targets behavioral dyscontrol, Stage 2 targets posttraumatic stress disorder (PTSD) via the DBT PE protocol, and Stage 3 addresses remaining problems. We evaluated the course of change in multiple outcomes across these three stages and compared them to changes found in DBT alone. METHOD: Participants were 38 women with BPD, PTSD and recent suicidal and/or non-suicidal self-injury. Data were collected weekly or bi-weekly to assess PTSD, BPD, global well-being, state dissociation, and urges to engage in problem behaviors. RESULTS: In DBT + DBT PE, there was a significant improvement in PTSD in Stage 2 and in PTSD, BPD, and state dissociation in Stage 3. Compared to DBT, DBT + DBT PE led to significantly higher global well-being and moderately, but non-significantly, lower PTSD and BPD in Stages 2 and/or 3. CONCLUSIONS: PTSD does not improve until it is directly targeted and changes in other comorbid problems occur after PTSD is treated. Adding the DBT PE protocol to DBT was associated with improvement rather than worsening of outcomes.

Blackout Drinking Predicts Sexual Revictimization in a College Sample of Binge-Drinking Women.

Sexual victimization is prevalent on U.S. college campuses. Some women experience multiple sexual victimizations with heightened risk among those with prior victimization histories. One risk factor for sexual revictimization is alcohol use. Most research has focused on associations between alcohol consumption and revictimization. The current study's objective was to understand potential mechanisms by which drinking confers risk for revictimization. We hypothesized that specific drinking consequences would predict risk for revictimization above and beyond the quantity of alcohol consumed. There were 162 binge-drinking female students (mean age = 20.21 years, 71.3% White, 36.9% juniors) from the University of Washington who were assessed for baseline victimization (categorized as childhood vs. adolescent victimization), quantity of alcohol consumed, and drinking consequences experienced, then assessed 30 days later for revictimization. There were 40 (24.6%) women who were revictimized in the following 30 days. Results showed that blackout drinking at baseline predicted incapacitated sexual revictimization among women previously victimized as adolescents, after accounting for quantity of alcohol consumed (OR = 1.79, 95% CI [1.07, 3.01]). Other drinking consequences were not strongly predictive of revictimization. Adolescent sexual victimization was an important predictor of sexual revictimization in college women; blackout drinking may confer unique risk for revictimization.

Treatment-related beliefs and reactions among trauma-focused therapy completers and discontinuers: A qualitative examination.

Prolonged exposure (PE) and cognitive processing therapy (CPT) for posttraumatic stress disorder (PTSD) are effective, but some patients do not respond adequately, and dropout rates are high. Patients' beliefs about treatment and perceptions of treatment components influence treatment outcomes and may be amenable to change through intervention. The present study sought to identify beliefs and reactions to PE and CPT that differentiated completers who screened negative for a PTSD diagnosis after treatment (PTSD-), completers who screened positive for a PTSD diagnosis after treatment (PTSD+), and discontinuers who attended six or fewer sessions. Thematic analysis was used to identify themes in qualitative data collected via retrospective semistructured interviews with 51 completers (19 PTSD- after treatment, 32 PTSD+ after treatment) and 66 discontinuers of PE/CPT. Participants were demographically diverse veterans across service eras. Treatment-related beliefs and reactions differentiating these groups included perceived helpfulness of treatment, self-efficacy in engaging in treatment, anticipatory anxiety and concerns, interpretations of ongoing symptoms, and perceived consequences of treatment on functioning. Further, some patterns seemed to differ in early treatment sessions compared to during the active components of treatment. Findings point to potentially malleable targets that could be intervened upon to improve trauma-focused treatment outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Antibody depletion for the treatment of crossmatch-positive pediatric heart transplant recipients.

Sensitization to HLA is a risk factor for adverse outcomes after heart transplantation. Requiring a negative prospective CM results in longer waiting times and increased waitlist mortality. We report outcomes in a cohort of sensitized children who underwent transplant despite a positive CDC CM+ using a protocol of antibody depletion at time of transplant, followed by serial IVIG administration. All patients <21 yrs old who underwent heart transplantation at Boston Children's Hospital from 1/1998 to 1/2011 were included. We compared freedom from allograft loss, allograft rejection, and serious infection between CM+ and CM- recipients. Of 134 patients in the cohort, 33 (25%) were sensitized prior to transplantation and 12 (9%) received a CM+ heart transplant. Serious infection in the first post-transplant year was more prevalent in the CM+ patients compared with CM- patients (50% vs. 16%; p = 0.005), as was HD-AMR (50% vs. 2%; p < 0.001). There was no difference in freedom from allograft loss or any rejection. At our center, children transplanted despite a positive CM had acceptable allograft survival and risk of any rejection, but a higher risk of HD-AMR and serious infection.

Provider perceptions of their patients' dropout from trauma-focused therapy for PTSD in the U.S. Veterans Health Administration.

OBJECTIVE: Many patients who initiate prolonged exposure (PE) and cognitive processing therapy (CPT) do not complete a full course, although little is known about how providers view PE and CPT dropout among their own patients. METHOD: Semistructured interviews were conducted with providers (n = 29) in the Veterans Health Administration to understand each provider's experience of dropout by a specific patient whom they treated using PE or CPT. Content analysis was used to categorize perceptions of dropout as negative, somewhat negative, or not negative. Themes associated with somewhat or not negative views of dropout were identified via inductive coding. RESULTS: Fourteen percent of providers viewed their patient's dropout from PE or CPT as wholly negative, 38% as somewhat negative, and 48% as not a negative outcome. Themes associated with viewing dropout as something other than wholly negative included belief that the patient would not benefit from treatment if they were not ready, the importance of maintaining the therapeutic relationship, the view that trauma-focused therapy was not what the patient needed or that the patient could benefit from other approaches, the impression that the patient had made some gains, and that patients are responsible for treatment engagement and have the right to disengage. CONCLUSIONS: Providers' perceptions of dropout from PE or CPT for individual patients were rarely viewed as entirely negative. Research is needed to help providers determine when patient dropout is an undesirable outcome and when efforts to reengage patients in trauma-focused treatment are warranted. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Divergent experiences of U.S. veterans who did and did not complete trauma-focused therapies for PTSD: A national qualitative study of treatment dropout.

Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) are first-line treatments for posttraumatic stress disorder (PTSD) and have been disseminated throughout the U.S. Veterans Health Administration. Treatment non-completion is common and lessens clinical effectiveness; however, prior work has failed to identify factors consistently associated with non-completion. Semi-structured interviews were conducted with a national sample of veterans who recently completed (n = 60) or did not complete (n = 66) PE or CPT. Non-completer interviews focused on factors that contributed to veterans' decisions to drop out and efforts undertaken to complete PE/CPT. Completer interviews focused on challenges faced in completing treatment and facilitators of completion. Transcripts were coded using a mixed deductive/inductive approach; constant comparison was used to identify differences between completers and non-completers. Completers and non-completers differed in the extent of treatment-specific therapist support received, therapists' flexibility in treatment delivery, the type of encouragement offered by the care team and social supports, their interpretation of symptom worsening, the perceived impact of treatment on functioning, and the impact of stressors on their treatment engagement. Treatment-specific therapist support, more patient-centered and flexible treatment delivery, leveraging the full care team, and addressing functional concerns are potential targets for PE and CPT engagement interventions.

PIGG defines the Emm blood group system.

Emm is a high incidence red cell antigen with eight previously reported Emm- probands. Anti-Emm appears to be naturally occurring yet responsible for a clinically significant acute hemolytic transfusion reaction. Previous work suggests that Emm is located on a GPI-anchored protein, but the antigenic epitope and genetic basis have been elusive. We investigated samples from a South Asian Indian family with two Emm- brothers by whole genome sequencing (WGS). Additionally, samples from four unrelated Emm- individuals were investigated for variants in the candidate gene. Filtering for homozygous variants found in the Emm- brothers and by gnomAD frequency of < 0.001 resulted in 1818 variants with one of high impact; a 2-bp deletion causing a frameshift and premature stop codon in PIGG [NM_001127178.3:c.2624_2625delTA, p.(Leu875*), rs771819481]. PIGG encodes for a transferase, GPI-ethanolaminephosphate transferase II, which adds ethanolamine phosphate (EtNP) to the second mannose in a GPI-anchor. The four additional unrelated Emm- individuals had various PIGG mutations; deletion of Exons 2-3, deletion of Exons 7-9, insertion/deletion (indel) in Exon 3, and new stop codon in Exon 5. The Emm- phenotype is associated with a rare deficiency of PIGG, potentially defining a new Emm blood group system composed of EtNP bound to mannose, part of the GPI-anchor. The results are consistent with the known PI-linked association of the Emm antigen, and may explain the production of the antibody in the absence of RBC transfusion. Any association with neurologic phenotypes requires further research.

Effectiveness of training methods for delivery of evidence-based psychotherapies: a systematic review.

BACKGROUND: Extensive efforts have been made to train mental health providers in evidence-based psychotherapies (EBPs); there is increasing attention focused on the methods through which providers are trained to deliver EBPs. Evaluating EBP training methods is an important step in determining which methods are most effective in increasing provider skill and improving client outcomes. METHODS: We searched MEDLINE (Ovid) and PsycINFO for randomized controlled trials published from 1990 through June 2019 that evaluated EBP training methods to determine the effectiveness of EBP training modalities on implementation (provider and cost) and client outcomes. Eligible studies (N = 28) were evaluated for risk of bias, and the overall strength of evidence was assessed for each outcome. Data was extracted by a single investigator and confirmed by a second; risk of bias and strength of evidence were independently rated by two investigators and determined by consensus. RESULTS: Overall, EBP training improved short-term provider satisfaction, EBP knowledge, and adherence compared to no training or self-study of training materials (low to moderate strength of evidence). Training in an EBP did not increase treatment adoption compared to no training or self-study. No specific active EBP training modality was found to consistently increase provider EBP knowledge, skill acquisition/adherence, competence, adoption, or satisfaction compared to another active training modality. Findings were mixed regarding the additive benefit of post-training consultation on these outcomes. No studies evaluated changes in provider outcomes with regards to training costs and few studies reported on client outcomes. LIMITATIONS: The majority of included studies had a moderate risk of bias and strength of evidence for the outcomes of interest was generally low or insufficient. Few studies reported effect sizes. The ability to identify the most effective EBP training methods was limited by low strength of evidence for the outcomes of interest and substantial heterogeneity among studies. CONCLUSIONS: EBP training may have increased short-term provider satisfaction, EBP knowledge, and adherence though not adoption. Evidence was insufficient on training costs and client outcomes. Future research is needed on EBP training methods, implementation, sustainability, client outcomes, and costs to ensure efforts to train providers in EBPs are effective, efficient, and durable. TRIAL REGISTRATION: The protocol for this review is registered in PROSPERO (CRD42018093381).

Feasibility pilot of a brief mindfulness intervention for college students with posttraumatic stress symptoms and problem drinking.

OBJECTIVE: A significant subset of college students experience PTSD symptoms, and many engage in problematic alcohol use. Some college students with PTSD symptoms may use alcohol and other substances to cope with their symptoms, and those with PTSD experience more negative alcohol and drug consequences than those without PTSD. Mindfulness-Based Interventions (MBIs) have been successfully utilized for individuals with PTSD or substance use disorders. However, to date, no studies have evaluated MBIs for college students with co-occurring PTSD symptoms and problem drinking. METHOD: This study was a feasibility pilot of a 4-week group loving-kindness meditation (LKM) intervention, a practice of intentionally directing well wishes to oneself and others. LKM was compared to referral to treatment as usual (RTAU) for non-treatment seeking college students (N=75) with PTSD symptoms and problem drinking. RESULTS: Overall, the LKM group had low to moderate feasibility and acceptability among college students, as recruitment was lower than expected and attendance at LKM groups was modest. Participants' PTSD symptoms, drinking quantity, and negative drinking consequences decreased, and state mindfulness increased over the course of the study, but there were no significant differences between LKM and RTAU on these outcomes. Additionally, higher coping drinking motives predicted greater PTSD symptoms and more drinking consequences over the course of the study. CONCLUSIONS: Effective interventions for college students with PTSD symptoms and problematic alcohol use are needed, especially for individuals who drink to cope with their PTSD symptoms. Future research on LKM that addresses the limitations of the current study is warranted.

Gender differences in rates and predictors of individual psychotherapy initiation and completion among Veterans Health Administration users recently diagnosed with PTSD.

OBJECTIVE: Most veterans with posttraumatic stress disorder (PTSD) who receive care from the Veterans Health Administration (VHA) do not receive individual psychotherapy. The purpose of this study was to explore gender differences in initiation and completion of a sufficient course (defined as attending 8 or more sessions) of individual psychotherapy among male and female VHA users recently diagnosed with PTSD. METHOD: Participants (N = 7,218) were veterans in a prospective national cohort survey of VHA users diagnosed with PTSD; oversampling was used to increase representation of women and minority veterans. RESULTS: Forty-two percent of the sample (40.1% of men, 52.3% of women) initiated individual psychotherapy within 6 months of their index PTSD diagnosis. Of those who initiated, 12.1% (10.8% of men, 17.7% of women) completed a sufficient course of individual psychotherapy. Women were generally more likely than men to initiate individual psychotherapy. However, we found an interaction between gender and age, such that younger men were more likely to initiate psychotherapy than older men; age was not significantly associated with initiation among women. Regarding completion of individual psychotherapy, an interaction between gender and beliefs about psychotherapy was found, such that men were less likely to complete individual psychotherapy when they held more negative beliefs about psychotherapy; these beliefs did not significantly impact female veterans' likelihood of completing psychotherapy. CONCLUSIONS: Overall, while female veterans are more likely than male veterans with PTSD to initiate individual psychotherapy, rates of initiation and completion of individual psychotherapy for both genders remain relatively low. Interventions are needed to increase engagement in individual psychotherapy, particularly for male veterans with PTSD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Renal transplantation in patients with positive lymphocytotoxicity crossmatches: one center's experience.

BACKGROUND: Sensitization to human leukocyte antigens remains an important barrier to successful renal transplantation. MATERIALS AND METHODS: Herein we describe our center's experience with a plasmapheresis-based desensitization protocol for highly sensitized patients. Twenty-nine patients had a positive T-cell or positive B-cell lymphocytotoxicity crossmatch against their donors. In some cases, baseline crossmatches were of high titer (e.g., 11 had baseline titers > or =1:32). RESULTS: Twenty-eight of 29 patients were rendered T-cell crossmatch negative and B-cell crossmatch negative/low positive and transplanted. None had hyperacute rejection but 11 (39%) had acute antibody mediated rejection. Median follow-up is 22 months: 25 of the 28 (89%) of allografts are still functioning with mean plasma creatinine 1.5 mg/dL. There was one death because of the transplant or immunsuppression, one case of cytomegalovirus disease and no cases of lymphoproliferative disease. CONCLUSION: This series provides further evidence of the high efficacy of plasmapheresis-based desensitization protocols. Even patients with high baseline crossmatch titers can be successfully desensitized and transplanted. Short- and medium-term outcomes are encouraging but longer-term data are needed.

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

BACKGROUND: There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens. METHODS: This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons. FINDINGS: We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage). INTERPRETATION: By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. FUNDING: National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

Effects of trauma and PTSD on self-reported physical functioning in sexual minority women.

OBJECTIVE: Sexual minority women (lesbians, bisexual women, and women who partner with women) experience high rates of trauma exposure, are more likely to develop posttraumatic stress disorder (PTSD), and have high rates of physical health problems compared with heterosexual women. The present study tested whether PTSD may be the mechanism through which trauma exposure affects self-reported physical functioning in this population. METHOD: In a sample of 857 sexual minority women, we examined the association between trauma exposure and worsening physical functioning (measured using the 12-item Short Form Health Survey) 2 years later, whether PTSD mediated this relationship, and if so, which PTSD symptom clusters best accounted for this mediation. RESULTS: Results showed that more Criterion A traumatic events experienced (based on DSM-IV) predicted greater decline in physical functioning 2 years later, and PTSD symptoms mediated this relationship, explaining 73% of the total effect. The arousal/reactivity symptom cluster was the only significant mediator, explaining 68% of the total effect. CONCLUSIONS: Results show that PTSD, and arousal/reactivity symptoms in particular, may be the mechanism through which traumatic events negatively impact self-reported physical functioning. These findings provide further evidence that, for this at risk population, treating PTSD as soon as possible after onset may improve long term physical functioning. (PsycINFO Database Record