U.S. Military Presence in the Persian Gulf: Challenges and Prospects

The author considers the critical questions of U.S. military presence in the Gulf, the challenges it faces, and the prospects that lay ahead. He relies, in his presentation and analysis, on a variety of regional sources including newspaper reports and personal interviews conducted in the United States and the Gulf region, as well as government and academic sources. The result is a comprehensive study, including policy recommendations for U.S. military and civilian decisionmakers that makes intelligible the complex subject of U.S.-Gulf relations.https://press.armywarcollege.edu/monographs/1826/thumbnail.jp

Security Implications of the Proliferation of Weapons of Mass Destruction in the Middle East

This monograph addresses the important question of the security implications for the nations of the region of the proliferation of weapons of mass destruction in the Middle East. The Strategic Studies Institute is pleased to offer the monograph as a contribution to the national security debate on this important issue. The author offers a unique perspective based on extensive interviews that he conducted in the region, and makes specific policy recommendations for U.S. military and civilian decisionmakers.https://press.armywarcollege.edu/monographs/1851/thumbnail.jp

Hizballah: Terrorism, National Liberation, or Menace?

The author reviews the history of Hizballah since its inception in 1982, and examines its role in the recent political turmoil of Lebanon and the region. Not only is Hizballah\u27s role central in the dispute over the Sheb\u27a Farms enclave between Lebanon and Israel, it is part of an entangled set of linkages involving Syria, Iran, the United States, the European Union, and the Palestinians. The challenge that Hizballah poses to U.S. policy in the Middle East involves complicated strategic issues, not merely problems of terrorism that could be dealt with by countermeasures.https://press.armywarcollege.edu/monographs/1818/thumbnail.jp

PRIMARY SPONTANEOUS PNEUMOTHORAX: CLINICAL PROFILE, SEASONALITY AND RECURRENCE OF 132 ADULT PATIENTS IN A UNIVERSITY HOSPITAL, KINGDOM OF SAUDI ARABIA

Objectives: The current study aimed to study the presenting features of Primary Spontaneous Pneumothorax (PSP) patients including demographic (gender, age, smoking, height and weight, Body mass index (BMI)), symptoms and seasonality among adult patients in KKUH during the period from 2010 to 2016. To describe the recurrence of PSP and length of hospital stay in patients who were managed surgically in KKUH during the period from 2010 to 2016. Methods: Quantitative, Observational, Retrospective, Case-series study. 132 Patients was studied who were diagnosed with primary spontaneous pneumothorax disease from Jan 2010 to Dec 2016 in King Khalid University Hospital were studied. Data was collected by reviewing the transfer sheet case report form (CRF), and by reviewing variables in medical records of PSP patients. Results: The mean age was 24.62 (S.D ±8.8) years old. 88.6% of patients were males (11.4% females). 59.8% were smokers and 40.2% were non-smoker. The (BMI) average was 19.4 kg/m2. The season of the attack was more in spring and summer accounting a 29.6% for each. 90.9% of the Patients were treated surgically. The average length of hospital stay after surgical management was 6.45 days (S.D ±3.15), recurrent after surgical management was (4.1%). Conclusion: Based on this case series study, majority of primary spontaneous pneumothorax (PSP) patients were male, at young age group, with low body mass index (BMI). Most of the admissions occurred in warm climate (spring/summer). Furthermore, short hospital stays, and low state of recurrence were noted among the patients treated surgically. Key words: (Primary Spontaneous Pneumothorax, variables, seasonality, recurrence

Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity

Human interleukin (IL) 1 receptor–associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3– and TLR4–interferon (IFN)-a/b pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells (PBMCs) did not induce the 11 non-IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly(I:C). The patients' individual cell subsets from both myeloid (granulocytes, monocytes, monocyte-derived dendritic cells [MDDCs], myeloid DCs [MDCs], and plasmacytoid DCs) and lymphoid (B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly(I:C) and lipopolysaccharide in MDCs and MDDCs. Most patients (22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent (13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease (9 out of 28; 32%). Almost half of the patients died (12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK-4–dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK-4–dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria

Low Penetrance, Broad Resistance, and Favorable Outcome of Interleukin 12 Receptor β1 Deficiency: Medical and Immunological Implications

The clinical phenotype of interleukin 12 receptor β1 chain (IL-12Rβ1) deficiency and the function of human IL-12 in host defense remain largely unknown, due to the small number of patients reported. We now report 41 patients with complete IL-12Rβ1 deficiency from 17 countries. The only opportunistic infections observed, in 34 patients, were of childhood onset and caused by weakly virulent Salmonella or Mycobacteria (Bacille Calmette-Guérin -BCG- and environmental Mycobacteria). Three patients had clinical tuberculosis, one of whom also had salmonellosis. Unlike salmonellosis, mycobacterial infections did not recur. BCG inoculation and BCG disease were both effective against subsequent environmental mycobacteriosis, but not against salmonellosis. Excluding the probands, seven of the 12 affected siblings have remained free of case-definition opportunistic infection. Finally, only five deaths occurred in childhood, and the remaining 36 patients are alive and well. Thus, a diagnosis of IL-12Rβ1 deficiency should be considered in children with opportunistic mycobacteriosis or salmonellosis; healthy siblings of probands and selected cases of tuberculosis should also be investigated. The overall prognosis is good due to broad resistance to infection and the low penetrance and favorable outcome of infections. Unexpectedly, human IL-12 is redundant in protective immunity against most microorganisms other than Mycobacteria and Salmonella. Moreover, IL-12 is redundant for primary immunity to Mycobacteria and Salmonella in many individuals and for secondary immunity to Mycobacteria but not to Salmonella in most

B cell–intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

Engagement of cytokine receptors by specific ligands activate Janus kinase–signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21–induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients

Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia:a descriptive genomic study

BACKGROUND: Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin. METHODS: Full genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85-95%, and four 30-50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done. FINDINGS: Three distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction. INTERPRETATION: We present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed. FUNDING: Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre