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ABSTRACTIn response to extreme violence and psychological abuse, survivors of modern slavery and human trafficking can experience complex mental health problems. Despite being a major public health issue, the evidence base for post-slavery mental health support needs and service provision is lacking. The aim of this study was to scope the mental health provisions available to survivors globally. A single point-in-time, Internet-based scoping study of on-line evidence sources was performed, guided by Levac and colleagues’ six-staged framework. Three hundred and twenty five service providers met the criteria. Most were located in Asia and South America, catered for a female population, and could be categorized as Christian Faith Based. Two overarching themes (Characteristics of Provision and Types of Mental Health Support) accounted for the results, each including ten sub-themes. Survivors’ mental healthcare was found to be informed by various models and to exist within a nexus of care whereby several services are offered to different vulnerable populations. Little information of evidence-based interventions and monitoring and evaluation was found. The study’s results are limited in scope of influence due to the Internet-based design and should be taken cautiously. More empirical, multidisciplinary, and multi-stakeholder research is required to improve understanding survivors’ support needs and to inform policies and practices that are culturally competent, survivor-centered, gender-inclusive and empowering.

Childhood cancer and its treatment often impact the haematopoietic and lymphatic systems, with immunological consequences. Immunological assessments are not routinely included in surveillance guidelines for most survivors of childhood cancer, although a robust body of literature describes immunological outcomes, testing recommendations, and revaccination guidelines after allogeneic haematopoietic cell transplantation. Survivorship care providers might not fully consider the impaired recovery of a child's immune system after cancer treatment if the child has not undergone haematopoietic cell transplantation. We did a scoping review to collate the existing literature describing immune function after childhood cancer therapy, including both standard-dose chemotherapy and high-dose chemotherapy with haematopoietic cell rescue. This Review aims to summarise: the principles of immunology and testing of immune function; the body of literature describing immunological outcomes after childhood cancer therapy, with an emphasis on the risk of infection, when is testing indicated, and preventive strategies; and knowledge gaps and opportunities for future research.

The detection of genomic sequences and their alterations is crucial for basic research and clinical diagnostics. However, current methodologies are costly and time-consuming and require outsourcing sample preparation, processing, and analysis to genomic companies. Here, we establish One-pot DTECT, a platform that expedites the detection of genetic signatures, only requiring a short incubation of a PCR product in an optimized one-pot mixture. One-pot DTECT enables qualitative, quantitative, and visual detection of biologically relevant variants, such as cancer mutations, and nucleotide changes introduced by prime editing and base editing into cancer cells and human primary T cells. Notably, One-pot DTECT achieves quantification accuracy for targeted genetic signatures comparable with Sanger and next-generation sequencing. Furthermore, its effectiveness as a diagnostic platform is demonstrated by successfully detecting sickle cell variants in blood and saliva samples. Altogether, One-pot DTECT offers an efficient, versatile, adaptable, and cost-effective alternative to traditional methods for detecting genomic signatures.

•FLC-MS can detect persistent light chains in a significant proportion of patients in a conventional hematologic CR.•Patients with no detectable FLC by FLC-MS have significantly better OS and organ response irrespective of conventional hematologic response.

Toll-like receptor 8 gain-of-function (TLR8 GOF) is a recently described inborn error of immunity due to germline or somatic mutations in the TLR8gene and characterized by severe neutropenia, infections, lymphoproliferation, humoral immune defects, and in some cases, bone marrow failure. Treatment of TLR8 GOF has been challenging to date, and guidance for optimal therapy is lacking. We describe the clinical characteristics and management of 10 patients with TLR8 GOF variants, including the first female patient and further clinical outcome on the 6 patients initially reported with this disease with a focus on the role of allogeneic hematopoietic cell transplantation (HCT).

Nontransfusion-dependent β-thalassemia (NTDβT) syndromes consist of β-thalassemia intermedia and moderate hemoglobin E/β thalassemias. They are characterized by varying degrees of chronic anemia and a wide spectrum of complications due to ineffective erythropoiesis and iron overload from chronic transfusions. Hydroxyurea (HU), an oral chemotherapeutic drug, is anticipated to decrease disease severity.

Aims and methodTwo police liaison and section 136 schemes were developed alongside police services at different sites within the same NHS trust. In one, a mental health nurse worked with frontline police attending incidents related to mental health. The other involved nurses providing advice from the police control room. Section 136 detentions were measured over two 6-month periods (6 months apart) before and after practice change. Data analysed included total numbers of section 136 assessments, outcomes following subsequent assessment, and relevant diagnostic and demographic factors. Association of any change in section 136 total numbers and proportion subsequently admitted was investigated in both sites.ResultsThe model involving a nurse alongside frontline police showed significant reduction in section 136 numbers (38%, P<0.01) as well as greater admission rates (P= 0.01). The scheme involving support within the police control room did not show any change in section 136 detention but showed a non-significant (P= 0.16) decrease in subsequent admission.Clinical implicationsMental health nurses working alongside frontline police officers can help improve section 136 numbers and outcomes.

SummaryTaking risks is a fundamental part of the human experience that supports personal growth. Therapeutic risk-taking enables patients to make decisions about their level of safety and to pursue goals. Promoting therapeutic risk-taking can be complex. Professionals can experience tension striving for a balance between the interests of the individual and societal pressures to control risk. This article examines therapeutic risk-taking, recognising the challenges to supporting it in practice and debating how they may be overcome.Learning Objectives• Be able to explain what therapeutic risk-taking is and discuss its application to psychiatric practice• Understand the factors that challenge and enable therapeutic risk-taking in psychiatric practice• Describe the association between therapeutic risk-taking and recovery

Aims and methodTwo police liaison and section 136 schemes were developed alongside police services at different sites within the same NHS trust. In one, a mental health nurse worked with frontline police attending incidents related to mental health. The other involved nurses providing advice from the police control room. Section 136 detentions were measured over two 6-month periods (6 months apart) before and after practice change. Data analysed included total numbers of section 136 assessments, outcomes following subsequent assessment, and relevant diagnostic and demographic factors. Association of any change in section 136 total numbers and proportion subsequently admitted was investigated in both sites.ResultsThe model involving a nurse alongside frontline police showed significant reduction in section 136 numbers (38%, P< 0.01) as well as greater admission rates (P= 0.01). The scheme involving support within the police control room did not show any change in section 136 detention but showed a non-significant (P= 0.16) decrease in subsequent admission.Clinical implicationsMental health nurses working alongside frontline police officers can help improve section 136 numbers and outcomes.

ADAGEN, a bovine-based enzyme replacement therapy (ERT), has been used to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2018, ADAGEN was replaced by REVCOVI (elapegademase), a modified bovine recombinant protein.

Workplace stress is prevalent among nurses. Healthcare employers have implemented complementary and alternative therapies (CATs) for relaxation and stress management within workplace wellbeing programmes. In-depth interviews were conducted with 12 registered nurses to explore the perceptions and experiences of nurses towards accessing CATs in and outside the workplace. Interviews were audio recorded and transcribed verbatim. Data were analysed using conventional, qualitative thematic techniques. Themes identified were ‘perceptions of complementary and alternative therapies for stress management’ and ‘engagement with workplace wellness schemes’. CATs have a role within workplace wellbeing programmes and nurses are not averse to accessing them, although there are barriers to access that need to be addressed.

This article discusses several models of Psychosis, research on Cognitive Behavior Therapy for Psychosis (CBTp) and recent developments and new directions in the theory and practice of CBTp. Throughout the article we focus on the evolution of the field of CBTp as well as issues and opportunities for the field. We have highlighted the evolution of a more humanistic and strengths-based approach to recovery in psychosis, which focuses to a greater extent on personal values and goals rather than symptoms, as compared to earlier CBT models for psychosis. We have also consolidated information related to trends and innovations in CBTp. In the spirit of clinical utility, we have emphasized and referenced clinical resources and practical materials on CBTp interventions. Finally, we highlight the need for further research, enhanced consumer involvement, and increased access and resources for those with lived experience of psychosis.

ABSTRACTThe acquisition of superantigen-encoding genes by Streptococcus pyogeneshas been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equiis linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equisubsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equisubsp. zooepidemicusstrains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel superantigen-encoding genes. The products of szeF, szeN, and szePshare 59%, 49%, and 34% amino acid sequence identity with SPEH, SPEM, and SPEL, respectively. Recombinant SzeF, SzeN, and SzeP stimulated the proliferation of equine peripheral blood mononuclear cells, and tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) production, in vitro. Although none of these superantigen genes were encoded within functional prophage elements, szeNand szePwere located next to a prophage remnant, suggesting that they were acquired by horizontal transfer. Eighty-one of 165 diverse S. equisubsp. zooepidemicusstrains screened, including 7 out of 15 isolates from cases of disease in humans, contained at least one of these new superantigen-encoding genes. The presence of szeNor szeP, but not szeF, was significantly associated with mitogenic activity in the S. equisubsp. zooepidemicuspopulation (P< 0.000001, P< 0.000001, and P= 0.104, respectively). We conclude that horizontal transfer of these novel superantigens from and within the diverse S. equisubsp. zooepidemicuspopulation is likely to have implications for veterinary and human disease.

The acquisition of superantigen-encoding genes by Streptococcus pyogenes has been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equi is linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equi subsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equi subsp. zooepidemicus strains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel superantigen-encoding genes. The products of szeF, szeN, and szeP share 59%, 49%, and 34% amino acid sequence identity with SPEH, SPEM, and SPEL, respectively. Recombinant SzeF, SzeN, and SzeP stimulated the proliferation of equine peripheral blood mononuclear cells, and tumor necrosis factor alpha (TNF-) and gamma interferon (IFN-) production, in vitro. Although none of these superantigen genes were encoded within functional prophage elements, szeN and szeP were located next to a prophage remnant, suggesting that they were acquired by horizontal transfer. Eighty-one of 165 diverse S. equi subsp. zooepidemicus strains screened, including 7 out of 15 isolates from cases of disease in humans, contained at least one of these new superantigen-encoding genes. The presence of szeN or szeP, but not szeF, was significantly associated with mitogenic activity in the S. equi subsp. zooepidemicus population (P < 0.000001, P < 0.000001, and P = 0.104, respectively). We conclude that horizontal transfer of these novel superantigens from and within the diverse S. equi subsp. zooepidemicus population is likely to have implications for veterinary and human disease.

ABSTRACTStreptococcus equiis the causative agent of strangles, the most frequently diagnosed infectious disease of horses worldwide. The disease is characterized by abscessation and swelling of the lymph nodes of the head and neck, which can literally strangle the horse to death. S. equiproduces four recently acquired phage-associated bacterial superantigens (sAgs; SeeH, SeeI, SeeL, and SeeM) that share homology with the mitogenic toxins of Streptococcus pyogenes. The aim of this study was to characterize the contribution of each of these S. equisAgs to mitogenic activity in vitroand quantify the sAg-neutralizing capacity of sera from naturally infected horses in order to better understand their role in pathogenicity. Each of the sAgs was successfully cloned, and soluble proteins were produced in Escherichia coli. SeeI, SeeL, and SeeM induced a dose-dependent proliferative response in equine CD4 T lymphocytes and synthesis of gamma interferon (IFN-γ). SeeH did not stimulate equine peripheral blood mononuclear cells (PBMC) but induced proliferation of asinine PBMC. Allelic replacement mutants of S. equistrain 4047 with sequential deletion of the superantigen genes were generated. Deletion of seeI, seeL, and seeMcompletely abrogated the mitogenic activity and synthesis of IFN-γ, in equine PBMC, of the strain 4047 culture supernatant. Sera from naturally infected convalescent horses had only limited sAg-neutralizing activities. We propose that S. equisAgs play an important role in S. equipathogenicity by stimulating an overzealous and inappropriate Th1 response that may interfere with the development of an effective immune response.

Streptococcus equi is the causative agent of strangles, the most frequently diagnosed infectious disease of horses worldwide. The disease is characterized by abscessation and swelling of the lymph nodes of the head and neck, which can literally strangle the horse to death. S. equi produces four recently acquired phage-associated bacterial superantigens (sAgs; SeeH, SeeI, SeeL, and SeeM) that share homology with the mitogenic toxins of Streptococcus pyogenes. The aim of this study was to characterize the contribution of each of these S. equi sAgs to mitogenic activity in vitro and quantify the sAg-neutralizing capacity of sera from naturally infected horses in order to better understand their role in pathogenicity. Each of the sAgs was successfully cloned, and soluble proteins were produced in Escherichia coli. SeeI, SeeL, and SeeM induced a dose-dependent proliferative response in equine CD4 T lymphocytes and synthesis of gamma interferon (IFN-). SeeH did not stimulate equine peripheral blood mononuclear cells (PBMC) but induced proliferation of asinine PBMC. Allelic replacement mutants of S. equi strain 4047 with sequential deletion of the superantigen genes were generated. Deletion of seeI, seeL, and seeM completely abrogated the mitogenic activity and synthesis of IFN-, in equine PBMC, of the strain 4047 culture supernatant. Sera from naturally infected convalescent horses had only limited sAg-neutralizing activities. We propose that S. equi sAgs play an important role in S. equi pathogenicity by stimulating an overzealous and inappropriate Th1 response that may interfere with the development of an effective immune response.

Chronic granulomatous disease (CGD), an immunodeficiency with recurrent pyogenic infections and granulomatous inflammation, results from loss of phagocyte superoxide production by recessive mutations in any 1 of 4 genes encoding subunits of the phagocyte NADPH oxidase. These include gp91phox and p22phox, which form the membrane-integrated flavocytochrome b, and cytosolic subunits p47phox and p67phox. A fifth subunit, p40phox, plays an important role in phagocytosis-induced superoxide production via a phox homology (PX) domain that binds to phosphatidylinositol 3-phosphate (PtdIns(3)P). We report the first case of autosomal recessive mutations in NCF4, the gene encoding p40phox, in a boy who presented with granulomatous colitis. His neutrophils showed a substantial defect in intracellular superoxide production during phagocytosis, whereas extracellular release of superoxide elicited by phorbol ester or formyl-methionyl-leucyl-phenylalanine (fMLF) was unaffected. Genetic analysis of NCF4 showed compound heterozygosity for a frameshift mutation with premature stop codon and a missense mutation predicting a R105Q substitution in the PX domain. Parents and a sibling were healthy heterozygous carriers. p40phoxR105Q lacked binding to PtdIns(3)P and failed to reconstitute phagocytosis-induced oxidase activity in p40phox-deficient granulocytes, with premature loss of p40phoxR105Q from phagosomes. Thus, p40phox binding to PtdIns(3)P is essential for phagocytosis-induced oxidant production in human neutrophils and its absence can be associated with disease.

Chronic granulomatous disease (CGD), an immunodeficiency with recurrent pyogenic infections and granulomatous inflammation, results from loss of phagocyte superoxide production by recessive mutations in any 1 of 4 genes encoding subunits of the phagocyte NADPH oxidase. These include gp91phoxand p22phox, which form the membrane-integrated flavocytochrome b, and cytosolic subunits p47phoxand p67phox. A fifth subunit, p40phox, plays an important role in phagocytosis-induced superoxide production via a phox homology (PX) domain that binds to phosphatidylinositol 3-phosphate (PtdIns(3)P). We report the first case of autosomal recessive mutations in NCF4, the gene encoding p40phox, in a boy who presented with granulomatous colitis. His neutrophils showed a substantial defect in intracellular superoxide production during phagocytosis, whereas extracellular release of superoxide elicited by phorbol ester or formyl-methionyl-leucyl-phenylalanine (fMLF) was unaffected. Genetic analysis of NCF4showed compound heterozygosity for a frameshift mutation with premature stop codon and a missense mutation predicting a R105Q substitution in the PX domain. Parents and a sibling were healthy heterozygous carriers. p40phoxR105Q lacked binding to PtdIns(3)P and failed to reconstitute phagocytosis-induced oxidase activity in p40phox-deficient granulocytes, with premature loss of p40phoxR105Q from phagosomes. Thus, p40phoxbinding to PtdIns(3)P is essential for phagocytosis-induced oxidant production in human neutrophils and its absence can be associated with disease.

OBJECTIVE: To assess changes in functional status in patients with rheumatoid arthritis (RA) receiving the interleukin-1 receptor antagonist anakinra in addition to a disease modifying antirheumatic drug (DMARD). METHODS: In this large, multicenter, open-label, single-arm study, adult patients with RA receiving methotrexate, sulfasalazine, or hydroxychloroquine for ≥ 3 months were given anakinra 100 mg once daily for up to 36 weeks. The primary objective was to evaluate changes from baseline to week 36 in the Health Assessment Questionnaire (HAQ) disability index and subscales. Changes in the 28-joint Disease Activity Score (DAS28), proportion of patients meeting European League Against Rheumatism (EULAR) response criteria, and the safety of each combination regimen were also assessed. RESULTS: A total of 1207 patients were enrolled, received ≥ 1 dose of anakinra, and were included in the efficacy and safety analyses. A statistically significant change in the HAQ disability index was observed (p = 0.0001); no significant differences were seen among the 3 DMARD groups. A clinically meaningful improvement in HAQ (> 0.22) was observed in 51% of patients. Mean improvement in DAS28 was 1.5 (p < 0.0001), and 64% of patients achieved a good or moderate EULAR response score. Injection site reaction was the most frequently (62%) reported adverse event. The incidence of infections (24%), most commonly respiratory infection, was similar across treatment groups. No notable changes were observed in laboratory findings and vital signs. CONCLUSION: These findings indicate that anakinra 100 mg/day in combination with DMARD therapy safely improved functional status in patients with active RA.

Background:The transmissibility of vaccine-strain viruses from immunocompromised patients, such as those with severe combined immune deficiency (SCID) is unknown. The infection control management of a patient diagnosed with SCID and infected with vaccine-strain varicella zoster virus (VZV) and measles virus is described below. A previously healthy, full-term boy was vaccinated at 14 months with measles mumps rubella varicella (MMR) vaccine. He had received prior vaccinations, including rotavirus, without adverse effects. During the 6 weeks after vaccination, the patient developed signs and symptoms clinically consistent with chicken pox and measles. An immune work-up revealed SCID. Methods:The Alberta Health Services (AHS) SCID protocol was followed to manage the patient upon admission at 17 months of age. Multiple meetings with various stakeholders were held to ensure appropriate precautions were followed to minimize the risk of pathogen transmission. Results:The patient was placed on airborne and contact precautions in a negative-pressure room. The pressure differential of the room to the corridor was continually monitored and displayed at the entry to the room. Staff known to be immune to VZV or measles were not required to wear an N95 respirator. All intrahospital movement of the patient was coordinated with the respective care teams and departments, including infection prevention and control, facilities maintenance and engineering, respiratory therapy, and diagnostic imaging. A mask was placed on the patient when movement outside the room was required. VZV testing was positive for the Oka/vaccine strain on all samples tested (ie, nasopharyngeal, skin, blood, and cerebrospinal fluid). Nasopharyngeal swabs and blood were PCR positive for measles genotype A/vaccine strain virus. Both viruses were persistently positive in spite of treatment with acyclovir, valganciclovir, varicella zoster immune globulin, and intravenous immune globulin. Conclusions:There is currently no documented transmission of measles vaccine-strain virus, and transmission of VZV vaccine-strain virus is rare. According to the AHS SCID protocol, the use of airborne and contact precautions for a patient identified with measles and/or VZV supersedes the use of a positive-pressure room for patients identified with SCID. Newborn screening for SCID was implemented in Alberta in June 2019. As a result, more SCID patients will be diagnosed earlier in their course, and therefore prior to most routine vaccinations. However, newborn screening will not pick up some types of combined immune deficiencies. Some children may still be at risk of vaccine-associated illnesses due to undiagnosed underlying immune deficiencies.Funding:NoneDisclosures:None

Introduction

Giles: The Binding Site: Research Funding. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company. Wright: The Binding Site: Current Employment. Cook: Pfizer: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding. Morgan: BMS: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Cairns: Takeda: Research Funding; Amgen: Research Funding; Merck Sharpe and Dohme: Research Funding; Celgene / BMS: Other: travel support, Research Funding. Menzies: Celgene / BMS: Research Funding; Amgen: Research Funding; Merck Sharpe and Dohme: Research Funding. Kaiser: AbbVie: Consultancy; Janssen: Consultancy, Other: Educational support, Research Funding; Karyopharm: Consultancy, Research Funding; Pfizer: Consultancy; Amgen: Honoraria; Seattle Genetics: Consultancy; Takeda: Consultancy, Other: Educational support; GSK: Consultancy; BMS/Celgene: Consultancy, Other: Travel support, Research Funding. Pawlyn: Amgen: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Jackson: oncopeptides: Consultancy; celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; amgen: Consultancy, Honoraria, Speakers Bureau; takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; J and J: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau. Pratt: Janssen: Consultancy; Gilead: Consultancy; Binding Site: Consultancy; Amgen: Consultancy; Takeda: Consultancy; BMS/Celgene: Consultancy.

Up to 80% of children with autism spectrum disorder (ASD) experience sleep disturbance. Poor sleep impairs executive functioning (EF), a lifelong difficulty in ASD. Evidence suggests EF difficulties in ASD are exacerbated by poor sleep. We examine whether early childhood sleep disturbances are associated with worsening EF trajectories in school-aged children with ASD. A subsample (n= 217) from the Pathways in ASDlongitudinal study was analyzed. The Children’s Sleep Habits Questionnairecaptured sleep duration, onset, and night awakenings before age 5 (mean = 3.5 years). Metacognition (MI) and Behavioral Regulation (BRI) indices, on the Teacher Behavior Rating Inventory of Executive Functioning, were used to measure cognitive and affective components of EF respectively at four time-points (7.8–11.8 years). We applied latent growth curve models to examine associations between sleep and EF, accounting for relevant covariates, including school-age sleep (mean = 6.7 years). Sleep traits had different age-related impacts on behavioral regulation, but not metacognition. Longer sleep onset at 3.5 years was associated with a worsening BRI difficulties slope (b= 2.07, p< 0.04), but conversely associated with lower BRI difficulties at 7.7 years (b= −4.14, p= 0.04). A longer sleep onset at 6.7 years was related to higher BRI difficulties at 7.7 years (b= 7.78, p< 0.01). Longer sleep duration at 6.7 years was associated with higher BRI difficulties at age 7.7 (b= 3.15, p= 0.01), but subscale analyses revealed shorter sleep duration at age 6.7 was linked to a worsening inhibition slope (b= −0.60, p= 0.01). Sleep onset is a robust early correlate of behavior regulation in children with ASD, whereas sleep duration is a later childhood correlate.

The article reports on the UK Research Reserve (UKRR), which is a coordinated, collaborative and sustainable strategy for securing the long-term maintenance, storage and access to printed research journals that are not often used. The three goals of the UKRR are: the protection of the long-term future of printed research journals; a quick and easy access to the research journals; and the efficient use of resources. The first phase of the project will include the development of a prototype system and testing an operational service for researchers. The second phase will open the UKRR system to all college libraries.

Background:

No relevant conflicts of interest to declare.

Chronic Granulomatous Disease is an inherited immunodeficiency resulting from a defect in one of 5 proteins necessary for the production of NADPH oxidase, an important component in managing infections by neutrophils. The most common form of the disease is X-linked due to mutations in the GP91 protein. Patients with CGD are thus prone to various infections from specific bacteria and/or fungi, but generally have normal viral responses. They are also prone to inflammatory diseases, including sarcoid, lupus, and colitis. Allogeneic hematopoieitic transplantation has been shown to be curative and will arrest or even reverse some of the inflammatory problems and is now more commonly used in patients with a history of inflammation or recurrent infections.

Off Label Use: Hydroxyurea is used in thalassemia for over two decades to reduce transfusion requirements and other purposes but its indications in thalassemia are not well recognized and accepted.. Viprakasit:Novartis: Honoraria, Research Funding; Shire co.: investigator in clinical trials, investigator in clinical trials Other.

Background:

Off Label Use: Hydroxyurea for β-Thalassemia.

Off Label Use: Hydroxyurea for β-Thalassemia.

Background

Background