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•Allogeneic HCT quickly and durably resolved disease manifestations in patients with CGD, with excellent survival.•HCT should be considered early for CGD before comorbidities affect the performance status.

•This first multicenter trial of MAC haplo-BMT with PTCy in pediatric patients with acute leukemias ahowed 0% TRM and 0% grade 3 or 4 aGVHD.•Our study shows low CuIs of grade 2 aGVHD and moderate-to-severe cGVHD and similar relapse rates as those of matched-donor BMT.

Severe combined immunodeficiency (SCID) is fatal unless durable adaptive immunity is established, most commonly through allogeneic haematopoietic cell transplantation (HCT). The Primary Immune Deficiency Treatment Consortium (PIDTC) explored factors affecting the survival of individuals with SCID over almost four decades, focusing on the effects of population-based newborn screening for SCID that was initiated in 2008 and expanded during 2010–18.

Adenosine deaminase (ADA) deficiency causes ∼13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 patients with ADA-SCID diagnosed between 1982 and 2017 who were enrolled in the Primary Immune Deficiency Treatment Consortium SCID studies. Baseline clinical, immunologic, genetic characteristics, and treatment outcomes were analyzed. First definitive cellular therapy (FDCT) included 56 receiving HCT without preceding ERT (HCT); 31 HCT preceded by ERT (ERT-HCT); and 33 GT preceded by ERT (ERT-GT). Five-year event-free survival (EFS, alive, no need for further ERT or cellular therapy) was 49.5% (HCT), 73% (ERT-HCT), and 75.3% (ERT-GT; P < .01). Overall survival (OS) at 5 years after FDCT was 72.5% (HCT), 79.6% (ERT-HCT), and 100% (ERT-GT; P = .01). Five-year OS was superior for patients undergoing HCT at <3.5 months of age (91.6% vs 68% if ≥3.5 months, P = .02). Active infection at the time of HCT (regardless of ERT) decreased 5-year EFS (33.1% vs 68.2%, P < .01) and OS (64.7% vs 82.3%, P = .02). Five-year EFS (90.5%) and OS (100%) were best for matched sibling and matched family donors (MSD/MFD). For patients treated after the year 2000 and without active infection at the time of FDCT, no difference in 5-year EFS or OS was found between HCT using a variety of transplant approaches and ERT-GT. This suggests alternative donor HCT may be considered when MSD/MFD HCT and GT are not available, particularly when newborn screening identifies patients with ADA-SCID soon after birth and before the onset of infections. This trial was registered at www.clinicaltrials.gov as #NCT01186913 and #NCT01346150.

Single fraction total body irradiation (SFTBI) as part of a myeloablative preparative regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for hematopoietic malignancies was shown to have similar survival compared with fractionated total body irradiation (FTBI)-containing regimens, with less acute toxicity. The objective of this study was to determine long-term toxicity >2 years following SFTBI-based HSCT. Twenty-one patients were evaluated at a median follow-up of 6.8 years. Thyroid dysfunction was found in 21 of patients, 1 of whom (5.2) was symptomatic; 23 had gonadal failure; 50 of patients with growth potential had linear growth disturbance; 27 had mild to moderate pulmonary disease; and 25 had cataracts. Intelligence quotient was stable. cGVHD was present in 28, and 4 patients (19) were on immune suppression 2 years posttransplant. Overall survival subsequent to 2 years posttransplant was 76 in this cohort of patients. No secondary malignancies were observed. In conclusion, the toxicities of SFTBI occurred at similar or reduced frequency compared with FTBI. SFTBI should be considered for patients who may benefit from a radiation-containing HSCT preparative regimen.

The article reports that American Academy of Pediatricians, the Children's Hospital Association, and the American Academy of Child and Adolescent Psychiatry recently stated that children's mental health is a national emergency. It mentions that the NH House approved House Bill1639, relative to the youth risk behavior survey in schools, over the objections of educators, students and advocates for children, mental health and community health centers, and substance use disorder providers.

The article focuses on the Improvements were driven by the customer experience, needs and interests, and inspiring to do better every day should not negate the accomplishments made over time.

X-linked inhibitor of apoptosis (XIAP) deficiency, caused by BIRC4mutations, is described to cause X-linked lymphoproliferative disease (XLP) phenotypes. However, compared with XLP caused by SLAM-Associated Protein deficiency (SH2D1Amutation), XIAP deficiency was originally observed to be associated with a high incidence of hemophagocytic lymphohistiocytosis (HLH) and a lack of lymphoma, suggesting that classification of XIAP deficiency as a cause of XLP may not be entirely accurate. To further characterize XIAP deficiency, we reviewed our experience with 10 patients from 8 unrelated families with BIRC4mutations. Nine of 10 patients developed HLH by 8 years of age. Most patients presented in infancy, and recurrent HLH was common. There were no cases of lymphoma. Lymphocyte defects thought to contribute to HLH development in SLAM-Associated Protein deficiency were not observed in XIAP deficiency. We conclude that XIAP deficiency is a unique primary immunodeficiency that is more appropriately classified as X-linked familial hemophagocytic lymphohistiocytosis.

X-linked inhibitor of apoptosis (XIAP) deficiency, caused by BIRC4 mutations, is described to cause X-linked lymphoproliferative disease (XLP) phenotypes. However, compared with XLP caused by SLAM-Associated Protein deficiency (SH2D1A mutation), XIAP deficiency was originally observed to be associated with a high incidence of hemophagocytic lymphohistiocytosis (HLH) and a lack of lymphoma, suggesting that classification of XIAP deficiency as a cause of XLP may not be entirely accurate. To further characterize XIAP deficiency, we reviewed our experience with 10 patients from 8 unrelated families with BIRC4 mutations. Nine of 10 patients developed HLH by 8 years of age. Most patients presented in infancy, and recurrent HLH was common. There were no cases of lymphoma. Lymphocyte defects thought to contribute to HLH development in SLAM-Associated Protein deficiency were not observed in XIAP deficiency. We conclude that XIAP deficiency is a unique primary immunodeficiency that is more appropriately classified as X-linked familial hemophagocytic lymphohistiocytosis.

Background:Deficiency of Xlinked inhibitor of apoptosis XIAP, caused by BIRC4gene mutations, is the second known cause of Xlinked lymphoproliferative disease XLP, a rare primary immunodeficiency that often presents with lifethreatening hemophagocytic lymphohistiocytosis HLH. Rapid diagnosis of the known genetic causes of HLH, including XIAP deficiency, facilitates the initiation of lifesaving treatment and preparation for allogeneic hematopoietic cell transplantation HCT. Until now, a rapid screening test for XIAP deficiency has not been available.Methods:To develop a flow cytometric screening test for XIAP deficiency, we first used lymphoblastic cell lines generated from controls and patients with BIRC4mutations to identify two commercially available antibodies specific for native intracellular XIAP. Next, we used these antibodies to study control whole blood leukocyte XIAP expression. We then studied XIAP expression in leukocytes from patients with XLP due to BIRC4mutations, maternal carriers, and patients following HCT.Results:XIAP was expressed by the majority of all whole blood nucleated cells in normal controls. In contrast, XIAP was absent or decreased in all lymphocyte subsets, monocytes and granulocytes from four unrelated patients with XLP due to BIRC4mutations. Bimodal distribution of XIAP expression was evident in two maternal carriers, with significant skewing toward cells expressing normal XIAP. Bimodal distribution was also observed in a patient following HCT.Conclusions:Flow cytometric analysis of intracellular XIAP provides a rapid screening test for XLP due to XIAP deficiency. It also allows carrier detection and can be used to monitor donor versus recipient reconstitution following HCT. © 2009 Clinical Cytometry Society

Adenosine deaminase (ADA) deficiency causes ~13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 ADA-SCID patients diagnosed between 1982-2017 who were enrolled in the Primary Immune Deficiency Treatment Consortium (PIDTC) SCID studies. Baseline clinical, immunologic, genetic characteristics and treatment outcomes were analyzed. First definitive cellular therapy (FDCT) included 56 receiving HCT without preceding ERT (HCT); 31 HCT preceded by ERT (ERT-HCT); and 33 GT preceded by ERT (ERT-GT). Five-year event free survival (EFS, alive, no need for further ERT or cellular therapy) was 49.5% (HCT), 73% (ERT-HCT), and 75.3% (ERT-GT) (p<0.01). Overall survival (OS) at 5-years after FDCT was 72.5% (HCT), 79.6% (ERT-HCT), and 100% (ERT-GT) (p=0.01). Five-year OS was superior for patients undergoing HCT at <3.5 months of age (91.6% vs. 68% if ≥3.5 months, p=0.02). Active infection at the time of HCT (regardless of ERT) decreased 5-year EFS (33.1% vs. 68.2%, p<0.01) and OS (64.7% vs. 82.3%, p=0.02). Five-year EFS (90.5%) and OS (100%) were best for matched sibling and matched family donors (MSD/MFD). For patients treated after the year 2000 and without active infection at the time of FDCT, no difference in 5-year EFS or OS was found between HCT using a variety of transplant approaches and ERT-GT. This suggests alternative donor HCT may be considered when MSD/MFD HCT and GT are not available, particularly when newborn screening identifies ADA-SCID patients soon after birth and before the onset of infections. Clinical trials: PIDTC 6901 study: ClinicalTrials.gov NCT01186913 PIDTC 6902 study: ClinicalTrials.gov NCT01346150

The etiology of the central nervous system (CNS) alterations after human immunodeficiency virus (HIV) infection, such as dementia and encephalitis, remains unknown. We have used microarray analysis in a monkey model of neuroAIDS to identify 98 genes, many previously unrecognized in lentiviral CNS pathogenesis, whose expression is significantly up-regulated in the frontal lobe of simian immunodeficiency virus-infected brains. Further, through immunohistochemical illumination, distinct classes of genes were found whose protein products localized to infiltrating macrophages, endothelial cells and resident glia, such as CD163, Glut5, and ISG15. In addition we found proteins induced in cortical neurons (ie, cyclin D3, tissue transglutaminase, α1-antichymotrypsin, and STAT1), which have not previously been described as participating in simian immunodeficiency virus or HIV-related CNS pathology. This molecular phenotyping in the infected brains revealed pathways promoting entry of macrophages into the brain and their subsequent detrimental effects on neurons. These data support the hypothesis that in HIV-induced CNS disease products of activated macrophages and astrocytes lead to CNS dysfunction by directly damaging neurons, as well as by induction of altered gene and protein expression profiles in neurons themselves which are deleterious to their function.

Provides information on the project to construct the corporate headquarters of Public Service of New Hampshire in Manchester. Value of the project; Reason for the delays in the project; use of green products and recycled materials in the construction.

Describes the Mobile Construction Automated Resource Management software from Receptive Technologies. Background of the company; Benefits of the product to construction firms; Key features of the product. INSET: Features and benefits of Receptive Technology's McArm.

Deals with the French Wing atrium built by the Society for the Protection of New Hampshire Forests in Concord incorporating a series of environmentally friendly products and processes. Features; Functions of the atrium; Background on the project.

Reports on the relocation of global information technology (IT) consultancy Auriga Inc. in the U.S. as a response to the shortage of IT specialists in the nation. Services offered by Auriga; Comparison between Russian and U.S. engineers.

Provides information on Xactitudes consulting and resource management firm. Company background; Range of clients; Aspects of the changing marketplace.

Features Rob Yonaitis, founder and president of Hiawatha Island Software. Work experiences of Yonaitis; Products of the company; Board members of the firm; Information on the accessibility issues pertaining to Web page design.

Provides information on the history and development of Greenville Wildlife Park in New Hampshire. Background on the owners and developers, Kathy and Glen Eldridge; Details on the varied animals; Health and maintenance of the animals; Challenges faced in operating the park.

Reports that Merrimack, New Hampshire-based Internet services company Ellacoya Networks Inc. is planning to create a new service provider business model. Reason behind the company's move; Overview on the business model planned to be created by the company; Potential advantages and drawbacks of the business model.

Features the Dirig Software company in the United States. Year established and founders; Growth in revenues; Flagship product; Technology used.

Reports on the production of the computer software Mobius Transportation Technology Solution (TTS) by Cadec Systems Inc. Recognition of the company as a market leader in transportation technology solutions; Company history; Features of Mobius TTS.

Reports on the establishment of CustomPins by Robert Kerens in Portsmouth, New Hampshire. Idea of Kerens from the sale of international flags; Elimination of the inventory after the start of the pin business; Benefit of the focus on design services.

Features Exeter, New Hampshire-based shoes and hats retailer Head Over Heels on Water Street. Business strategies utilized; Features of products offered; Profitability of the business.

Features the Dragon Dictate voice recognition computer software from Compucare Co. Functionality and applications; Price; Advantages offered to computer users.

Features Manchester, New Hampshire-based high technology company Brac Solutions. Products and services offered; Company origin; Growth initiatives undertaken.

Focuses on the technology offered by Full Circle Imaging to create spinning image advertising. Potential applications; Technology features and functions; Niche markets targeted by the company.

Presents a corporate profile of Mainstream Electronic Information Services Inc. located in Merrimack, New Hampshire. Business activity; Shift in focus toward developing commercial Internet applications.

Features WebSites.com Inc., a Derry, New Hampshire-based Web design and production firm. Company history; Key executives; Overview of the company's business operation; Major clients; Growth strategy.

Focuses on the efforts of New Hampshire-based cemetery and mortuary administration and management software developer Hanlon Management Information Services in its transition from DOS-based to Windows-based operating system. Complexity of the software offered by the company; Thirteen modules comprising the software program; Growth of the company.

Reports on the growth of New Hampshire-based computer software company Granite Systems Inc. Company's ranking in the 1999 New England Technology Fast 50; Increase in the company's revenues; Company as provider of engineering and operations support solutions.

Provides information on high technology firm Pragmatech. Revenues of the firm for 1999; Profile on the firm's founders; Profitability of the firm's computer software called the Request For Proposal Machine.

Focuses on the business growth at Hampstead, New Hampshire-based circuit board component maker Johnson & Johnston Associates. Celebration of 25th year in business in 1999; Consolidation of buildings and locations into a single operation; Background on founding in 1974 by partners John Johnston and Eddie Johnson; Agenda for growth outlined by company president Albert Burgun.

Features Dover, New Hampshire-based TTLC Internet. Details on the formation of the company according to founder Steve Viel; Financial and operational difficulties experienced by the company; Sales growth; Services. INSET: Taking, then giving back to the community.

Features Salem, New Hampshire-based telephone systems firm Bizfon. Company background; Products and services offered.

Features Hanover, New Hampshire-based Tally Systems Corp., developer of technology resource management software solutions. Factors leading to systems chaos on the desktop; Ted Jastrzembski as president and chief executive officer; Company history; Reasons for selecting the company's location; Tech and customer support; Construction of a building at Centerra Business and Retail Park.

Reports on the success of Goffstown, New Hampshire-based MuShield Co., a company that designs, makes prototypes and produces magnetic shielding. Usage of a state-of-the-art laser that enables the clean and precise cutting of metals; Factors contributing to the success; Background on the company.

Focuses on the success of Hudson, New Hampshire-based Brookshield Rapid Solutions' President Steve Ettelson and his partners in the rapid prototyping business. Product development support services offered; Factors contributing to the success; Company's range of customers.

Features New Hampshire-based technological firm, GZA GeoEnvironmental Technologies Inc. Developer of computer information systems for environmental health and safety managers; Formation of an Information Systems Division to exploit the World Wide Web; Advantages of using an intranet.

Relates the success story of Greenland, New Hampshire-based digital mapping company Maptech. Company's specialization in land and nautical digital mapping technology; Details of how the company creates digital maps of states; Publication of the maps on CD-ROMs; Company history and operations.

Focuses on DMC's electronics resale depot in New Hampshire. Mascot called Neddy; Development of recycling programs for other companies.

Features the participants to the Seacoast Chambers Business Expo at the Whittemore Center in Durham, New Hampshire on September 18, 1997. Lou Atlman of Customer Connections; Dan Burbank of Order Processing International; David Hodgdon of Portsmouth Computer Group; George Perrine of DuraSys Corp.; Jean Graunke of TMS Architects; Gregory Heyn of Real Estate Tax Services.

Features the Silknet ServiceDesk from Silknet Software Inc., a software system designed to allow companies to deliver excellent customer service. Comment on how the system works and how the problem-resolution database operates by Silknet President, Jay Wood; Various Web tools used by support person; Advantages of the graphics in relaying information; Ranges of license fees for the system.

Reports on the use by 1-800-Courier Inc. of satellite tracking equipment to keep track of deliveries on time. Same-day delivery promise; Training of drivers; Responsibility for driving records; Review of routes the drivers take; Preparation in the database prior to switch to a call center.