ABSTRACT
BACKGROUND: A modified grass allergen subcutaneous immunotherapy (SCIT) product with MicroCrystalline Tyrosine and monophosphoryl lipid-A as an adjuvant system (Grass MATA MPL [PQ Grass]) is being developed as short-course treatment of grass-pollen allergic rhinitis (SAR) and/or rhinoconjunctivitis. We sought to evaluate the combined symptom and medication score (CSMS) of the optimized cumulative dose of 27,600 standardized units (SU) PQ Grass in a field setting prior to embarking on a pivotal Phase III trial. METHODS: In this exploratory, randomized, double-blind, placebo-controlled trial subjects were enrolled across 14 sites (Germany and the United States of America). Six pre-seasonal subcutaneous injections of PQ Grass (using conventional or extended regimens) or placebo were administered to 119 subjects (aged 18-65 years) with moderate-to-severe SAR with or without asthma that was well-controlled. The primary efficacy endpoint was CSMS during peak grass pollen season (GPS). Secondary endpoints included Rhinoconjunctivitis Quality of Life Questionnaire standardized (RQLQ-S) and allergen-specific IgG4 response. RESULTS: The mean CSMS compared to placebo was 33.1% (p = .0325) and 39.5% (p = .0112) for the conventional and extended regimens, respectively. An increase in IgG4 was shown for both regimens (p < .01) as well as an improvement in total RQLQ-S for the extended regimen (mean change -0.72, p = .02). Both regimens were well-tolerated. CONCLUSIONS: This trial demonstrated a clinically relevant and statistically significant efficacy response to PQ Grass. Unprecedented effect sizes were reached for grass allergy of up to ≈40% compared to placebo for CSMS after only six PQ Grass injections. Both PQ Grass regimens were considered equally safe and well-tolerated. Based on enhanced efficacy profile extended regime will be progressed to the pivotal Phase III trial.
ABSTRACT
BACKGROUND: Excessive fascial tension is a major cause of ventral hernia recurrence. Although hernias are commonly characterized by area, the tension experienced by fascia is directly proportional to the surrounding tissue stiffness. We demonstrate an accurate and simple technique for intra-operative measurement of fascial closing tension and quantify the decrease in tension following Component Separation (CS). METHODS: A tensiometer was created using a spring with a known recoil constant (k) and a surgical clamp. Using Hooke's law (Force = kX; X = spring displacement), fascial tension was calculated. This method was first validated on a bench-top model and then applied to the anterior fascia of 4 fresh cadavers (8 hemi-abdomens) over a range of simulated hernia defect sizes. When fascia could no longer reach midline, CS was performed and measures repeated. Tissue stiffness was calculated by plotting defect size versus resulting tension. RESULTS: Fascial defects ranged from 1- to 18-cm wide with average midline closing tension prior to release 36.1 N (range 17-48) and 8.2 N (range 5-11) after CS, a mean 76% decrease (range 70%-85%). Mean R2 values between defect size and tension for the synthetic and cadaver models were 0.99 (p < 0.01) and 0.91 (p = 0.01; all hemi-abdomen measurements significant). Inter-rater Pearson's correlation consistently found R2 values > 0.95 (p < 0.01) for each hemi-abdomen, showing high precision and reproducibility. CONCLUSION: We have applied a cheap, simple, and precise method to sterilely assess fascial tension during herniorrhaphy and also quantified the decrease in tension following component separation. This technique may be rapidly translated into the operating room with minimal equipment to provide objective data critical for intraoperative decision-making.
Subject(s)
Hernia, Ventral , Herniorrhaphy , Cadaver , Fascia , Hernia, Ventral/surgery , Humans , Reproducibility of Results , Surgical MeshABSTRACT
Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle-aged women. It usually lasts for several years (> 1 year in 25-75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1 -antihistamines, even at higher doses, and third- and fourth-line therapies (omalizumab and ciclosporin) control the disease only in two-thirds of H1 -antihistamine-resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health-related quality of life (HRQoL), particularly when CSU is associated with angio-oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio-oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
Subject(s)
Chronic Urticaria , Urticaria , Chronic Disease , Europe , Female , Humans , Middle Aged , Omalizumab/therapeutic use , Quality of Life , Urticaria/drug therapy , Urticaria/epidemiologyABSTRACT
Background: Spinal cord stimulation is an established treatment option for certain chronic pain conditions which have been previously unresponsive to conservative therapies or potentially for a subset of patients who have not improved following spine surgery. Prior to permanent lead implantation, stimulator lead trials are performed to ensure adequate patient benefit. During these trials, one of the most common complications and reasons for failure is the displacement and migration of the trial leads, resulting in lost therapeutic coverage. Other complications include infection and dislodged bulky dressings. There is a paucity of literature describing an adequate procedural method to prevent these common complications. Objective: This study utilizes a series of 19 patients to evaluate a new technique for securing percutaneous spinal cord simulator trial leads, which may minimize dislodgement and migration complications and improve the rate of trial success. Study Design: Retrospective case series. Setting: New Jersey Medical School, Department of Anesthesiology, Pain Management Division. Methods: A retrospective chart review was conducted on 19 consecutive patients undergoing placement of the percutaneous thoracic spinal cord stimulator trial leads for pain associated with lumbar spine pathology over a two-year period (2010-2012). Results: Of the 19 patients in our cohort, there was one trial lead displacement, no lead migrations, and no site infections. Thirteen patients went on to permanent lead implantation. This improved trial lead placement technique had a high success rate with a low number of complications. Limitations: Small sample size, retrospective case series, and no control group for comparison. Conclusion: This case series was able to demonstrate that our described novel spinal cord stimulator trial lead placement and dressing technique can decrease the incidence of lead displacement and migration, thus improving trial success.
Subject(s)
Electrodes, Implanted/adverse effects , Foreign-Body Migration/prevention & control , Neurosurgical Procedures/methods , Spinal Cord Stimulation/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pain Management/methods , Retrospective StudiesABSTRACT
There have been case reports of proximal femur insufficiency fractures in patients who have previously undergone bariatric surgery. We present a follow-up case of a patient who developed bilateral complete proximal femur insufficiency fractures several years after bariatric surgery. Our patient underwent bilateral intramedullary fixation with a satisfactory postoperative outcome. We review and discuss the definition and pathogenesis of atypical femur fractures (AFFs), which may represent a larger category of insufficiency fractures not exclusive to bisphosphonate use, which includes patients with fractures after bariatric surgery.
Subject(s)
Gastric Bypass/adverse effects , Hip Fractures/etiology , Postoperative Complications/etiology , Female , Fracture Fixation, Intramedullary , Hip Fractures/diagnostic imaging , Hip Fractures/surgery , Humans , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/surgery , Radiography , Tomography, X-Ray ComputedABSTRACT
We report the case of a 24-year-old woman with a large hepatic adenoma diagnosed in the third trimester of pregnancy. The adenoma was at risk of rupture. She underwent scheduled preterm cesarean delivery under combined spinal-epidural anesthesia, followed by transarterial embolization on post-partum day six. Definitive resection of the adenoma took place two months postpartum.
Subject(s)
Adenoma/therapy , Anesthesia, Obstetrical/methods , Liver Neoplasms/therapy , Pregnancy Complications, Neoplastic/therapy , Adult , Anesthesia, Epidural , Anesthesia, Spinal , Embolization, Therapeutic , Female , Humans , PregnancyABSTRACT
The concept of quaternary prevention, resulting from a reflection on the doctor-patient relationship, is presented as a renewal of the ageold ethical requirement: first, a doctor must not harm; second, the doctor must control himself/herself. The origin of the concept, its endorsement by the World Organization of Family Doctors (WONCA) and the European Union of General Practitioners (UEMO), its dissemination, and the debates to which it has given rise, are presented by a panel of authors from 12 countries and 3 continents. This collective text deals more specifically with the ethics of prevention, the importance of teaching Quaternary prevention and Evidence Based Medicine, the social and political implications of the concept of quaternary prevention, and its anthropological dimensions.
Le concept de prévention quaternaire, issu d'une réflexion sur la relation médecin-patient, est présenté d'une part comme un renouvellement d'une exigence éthique séculaire ; d'abord ne pas nuire et d'autre part comme un plaidoyer pour un autocontrôle du médecin. L'origine du concept, son approbation par l'Organisation Mondiale des Médecins de Famille (WONCA) et l'Union Européenne des Médecins Omnipraticiens (UEMO), sa diffusion et les débats auxquels il a donné lieu, sont présentés par un panel d'auteurs de 12 pays et trois continents. Ce texte collectif traite plus spécifiquement de l'éthique de la prévention, de l'importance de l'enseignement de la prévention quaternaire et de la médecine factuelle, des implications sociales et politiques du concept de prévention quaternaire et de ses dimensions anthropologiques.
Subject(s)
Preventive Health Services , Anthropology , Humans , Politics , Preventive Health Services/ethics , Sociological FactorsABSTRACT
BACKGROUND: Effective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo. METHODS: OPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks. RESULTS: A total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated. CONCLUSIONS: Although this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
Subject(s)
Angioedemas, Hereditary/prevention & control , Enzyme Inhibitors/therapeutic use , Plasma Kallikrein/antagonists & inhibitors , Administration, Oral , Adult , Angioedemas, Hereditary/diagnosis , Angioedemas, Hereditary/drug therapy , Disease Progression , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Enzyme Inhibitors/pharmacokinetics , Female , Humans , Male , Middle Aged , Quality of Life , Recurrence , Treatment OutcomeABSTRACT
This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.
Subject(s)
Urticaria/diagnosis , Urticaria/therapy , Disease Management , Europe , Health Services Needs and Demand , Humans , Research , Urticaria/etiologyABSTRACT
BACKGROUND: Workplace exposure to trimellitic anhydride (TMA) can elicit TMA-specific IgE (sIgE), which may lead to occupational asthma (OA). An occupational immunosurveillance program (OISP) has been implemented to monitor TMA exposure and immunologic outcomes. The purpose of this study was to determine whether TMA-specific IgG (sIgG) responses can discriminate between TMA-exposed workers with and without sIgE responses. METHODS: Serum TMA-specific antibody (IgG, IgG4, and IgE) levels were estimated longitudinally (years 2006 to 2014) in TMA-exposed workers recruited in low, medium, and high exposure areas. sIgG and sIgE titers plotted against exposure duration were compared between workers with (a) sIgG only and (b) with sIgG who developed sIgE. RESULTS: Among 92 TMA-exposed workers continuously monitored for sIgG and sIgE, 38 developed sIgG; 11 developed a sIgE response 342.38 ± 186.03 days posthire and were removed from exposure. The average detection time of sIgG in removed workers (159 ± 92 days) was significantly shorter than for actively exposed workers with only sIgG (346 ± 187 days). Workers with earlier sIgG responses of higher titer (mean value 42.25 µg/mL) compared to delayed responders with lower sIgG titers (mean value 14.79 µg/mL) more frequently developed sIgE responses. Hierarchical clustering showed the initial magnitude and exposure time required for detectable sIgG production discriminated between workers with only sIgG from workers who subsequently produced sIgE. CONCLUSIONS: This study demonstrates the utility of longitudinally monitoring TMA-specific antibodies in an OISP as exposed workers with early sIgG responses and of higher magnitude are more likely to develop TMA sIgE sensitization.
Subject(s)
Asthma, Occupational/diagnosis , Immunoglobulin G/blood , Monitoring, Immunologic/methods , Occupational Exposure/analysis , Phthalic Anhydrides/adverse effects , Asthma, Occupational/blood , Asthma, Occupational/chemically induced , Humans , Immunoglobulin E , Occupational Exposure/adverse effects , Phthalic Anhydrides/immunologyABSTRACT
BACKGROUND: Most cardiac arrest (CA) patients remain comatose post-resuscitation, prompting goals-of-care (GOC) conversations. The impact of these conversations on patient outcomes has not been well described. METHODS: Patients (n=385) treated for CA in Columbia University ICUs between 2008-2015 were retrospectively categorized into various modes of survival and death based on documented GOC discussions. Patients were deemed "medically unstable" if there was evidence of hemodynamic instability at the time of discussion. Cerebral performance category (CPC) greater than 2 was defined as poor outcome at discharge and one-year post-arrest. RESULTS: The survival rate was 31% (n=118); most commonly after early recovery without any discussions (57%, n=67), followed by survival due to family wishes despite physicians predicting poor neurological prognosis (20%, n=24), and then survival after physician/family agreement of favorable prognosis (17%, n=20). The survivors due to family wishes had significantly worse outcomes compared to the early recovery group (discharge: p=0.01; one-year: p=0.06) and agreement group (p<0.001; p<0.001), though 2 patients did achieve favorable recovery. Among nonsurvivors (n=267), withdrawal of life-sustaining therapy (WLST) while medically unstable was most common (31%; n=83), followed by death after care was capped (24%, n=65), then WLST while medically stable (17%, n=45). Death despite full support, brain death and WLST due to advanced directives were less common causes. CONCLUSIONS: Most survivors due to family wishes despite poor neurological prognosis die or have poor outcomes at one-year. However, a small number achieve favorable recovery, demonstrating limitations with current prognostication methods. Among nonsurvivors, most WLST occurs while medically unstable, suggesting an overestimation of WLST due to unfavorable neurological prognosis.
Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest/mortality , Withholding Treatment/statistics & numerical data , Clinical Decision-Making/methods , Coma/etiology , Family , Heart Arrest/classification , Humans , Nervous System Diseases/etiology , Outcome and Process Assessment, Health Care , Prognosis , Recovery of Function , Retrospective Studies , Survival RateABSTRACT
Escalating obesity rates have become a significant public health problem in the Middle East and North Africa (MENA) region and have been associated with shifts towards a westernized diet. This integrative review aimed to examine the current dietary trends and transitions and their association with obesity in Arabic-speaking countries of the MENA region. Relevant databases were searched for studies in MENA countries between 1998 and 2014 that investigated obesity trends and changes in dietary patterns at the regional level in all age groups. A total of 39 articles fulfilled the inclusion criteria. All the articles noted that obesity was increasingly prevalent and that there was a significant dietary shift away from traditional dietary patterns; 51% reported a shift towards a westernized diet and half found that the western diet was correlated with increased obesity. Culturally relevant dietary health education and health promotion strategies are warranted to address both the dietary shifts towards the westernized diet and the increasing obesity.
Subject(s)
Diet/trends , Obesity/etiology , Adolescent , Adult , Africa, Northern/epidemiology , Bibliometrics , Child , Diet, Western/adverse effects , Feeding Behavior , Humans , Middle East/epidemiology , Obesity/epidemiology , Public Health , Young AdultABSTRACT
BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF.
Subject(s)
Abnormalities, Multiple/genetics , Dandy-Walker Syndrome/genetics , Developmental Disabilities/genetics , Facial Bones/abnormalities , Repressor Proteins/genetics , Abnormalities, Multiple/physiopathology , Bronchomalacia/genetics , Bronchomalacia/physiopathology , Dandy-Walker Syndrome/physiopathology , Developmental Disabilities/physiopathology , Exome/genetics , Face/physiopathology , Facial Bones/physiopathology , Female , Hallux Valgus/genetics , Hallux Valgus/physiopathology , High-Throughput Nucleotide Sequencing , Humans , Infant, Newborn , Male , PhenotypeABSTRACT
BACKGROUND: Approximately 50% of patients with chronic idiopathic/spontaneous urticaria (CIU/CSU) report hives and angioedema; some experience hives/angioedema only. OBJECTIVE: Assess omalizumab's effect on angioedema and quality of life (QoL) in subgroups with refractory CIU/CSU: those with and without angioedema. METHODS: Patients received omalizumab (75, 150 or 300 mg) or placebo every 4 weeks for 12/24 weeks. Angioedema and QoL were assessed [Urticaria Patient Daily Diary and Dermatology Quality of Life Index (DLQI)]. Subgroups were based on the presence/absence of baseline angioedema 7 days prior to randomization. RESULTS: Patients with baseline angioedema randomized to omalizumab 300 mg had a greater reduction in mean weekly incidence of angioedema and mean number of days/week with angioedema vs. placebo at 12 and 24 weeks. A 3.3- to 4.5-point greater mean reduction in DLQI score was achieved with omalizumab 300 mg treatment vs. placebo, above the minimal clinically important difference threshold. Results with lower doses vs. placebo were variable. CONCLUSION: Compared with placebo, omalizumab 300 mg treatment over 12-24 weeks resulted in marked reduction in incidence and number of days/week with angioedema accompanied by clinically relevant improvement in QoL.
Subject(s)
Angioedema/drug therapy , Omalizumab/therapeutic use , Quality of Life , Urticaria/drug therapy , Adult , Angioedema/complications , Female , Humans , Male , Middle Aged , Placebos , Urticaria/complications , Urticaria/physiopathologyABSTRACT
Escalating obesity rates have become a significant public health problem in the Middle East and North Africa [MENA] region and have been associated with shifts towards a westernized diet. This integrative review aimed to examine the current dietary trends and transitions and their association with obesity in Arabic-speaking countries of the MENA region. Relevant databases were searched for studies in MENA countries between 1998 and 2014 that investigated obesity trends and changes in dietary patterns at the regional level in all age groups. A total of 39 articles fulfilled the inclusion criteria. All the articles noted that obesity was increasingly prevalent and that there was a significant dietary shift away from traditional dietary patterns; 51% reported a shift towards a westernized diet and half found that the western diet was correlated with increased obesity. Culturally relevant dietary health education and health promotion strategies are warranted to address both the dietary shifts towards the westernized diet and the increasing obesity
L'augmentation rapide des taux d'obésité est devenue un problème de santé publique significatif dans la région du Moyen-Orient et de l'Afrique du Nord [MENA] et est associée à une occidentalisation des habitudes alimentaires. Le présent examen intégratif visait à étudier les tendances et les transitions alimentaires actuelles ainsi que leurs associations à l'obésité dans des pays arabophones de la région MENA. Des recherches ont été menées dans des bases de données pertinentes afin de trouver des études réalisées dans les pays de la région MENA entre 1998 et 2014 portant sur les tendances de l'obésité et les changements d'habitudes alimentaires parmi tous les groupes d'âge au niveau régional. Au total, 39 articles répondaient au critère d'inclusion. Tous les articles mentionnaient que l'obésité était de plus en plus prévalente et qu'un éloignement notable des habitudes alimentaires traditionnelles s'opérait. En effet, 51% des articles rapportaient une occidentalisation de l'alimentation, et la moitié concluait qu'il y avait une corrélation entre l'alimentation occidentale et l'augmentation de l'obésité. Une éducation en santé alimentaire et des stratégies de promotion de la santé pertinentes d'un point de vue culturel sont requises pour s'attaquer à la question de l'occidentalisation des habitudes alimentaires et de l'augmentation de l'obésité
Subject(s)
Obesity , Public Health , Diet, Healthy , Health Education , Health PromotionABSTRACT
SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR) <10th percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.
ABSTRACT
We report the experimental observation and computational analysis of the binary tin-carbon gas phase species. These novel ionic compounds are generated by impact of C60(-) anions on a clean tin target at some kiloelectronvolts kinetic energies. Positive Sn(m)C(n)(+) (m = 1-12, 1 ≤ n ≤ 8) ions were detected mass spectrometrically following ejection from the surface. Impact induced shattering of the C60(-) ion followed by sub-surface penetration of the resulting atomic carbon flux forces efficient mixing between target and projectile atoms even though the two elements (Sn/C) are completely immiscible in the bulk. This approach of C60(-) ion beam induced synthesis can be considered as an effective way for producing novel metal-carbon species of the so-called non-carbide forming elements, thus exploring the possible onset of molecular level miscibility in these systems. Sn2C2(+) was found to be the most abundant carbide cluster ion. Its instantaneous formation kinetics and its measured kinetic energy distribution while exiting the surface demonstrate a single impact formation/emission event (on the sub-ps time scale). Optimal geometries were calculated for both neutral and positively charged species using Born-Oppenheimer molecular dynamics for identifying global minima, followed by density functional theory (DFT) structure optimization and energy calculations at the coupled cluster singles, doubles and perturbative triples [CCSD(T)] level. The calculated structures reflect two distinct binding tendencies. The carbon rich species exhibit polyynic/cummulenic nature (tin end capped carbon chains) while the more stoichiometrically balanced species have larger contributions of metal-metal bonding, sometimes resulting in distinct tin and carbon moieties attached to each other (segregated structures). The Sn2C(n) (n = 3-8) and Sn2C(n)(+) (n = 2-8) are polyynic/cummulenic while all neutral Sn(m)C(n) structures (m = 3-4) could be described as small tin clusters (dimer, trimer, and tetramer, correspondingly) attached to a nearly linear carbon chain. For example, the 1:1 (Sn:C) Sn3C3 and Sn4C4 clusters are composed of all-tin triangle and rhombus, correspondingly, with a short carbon chain (C3, C4) attached on top. The cationic Sn3C(n)(+) (n = 1-5) and Sn4C(n)(+) (n = 1-4) species exhibit various intermediate geometries. Structure calculations at the CCSD(T) level are essential since the segregation effect is not as easily evident based on the most stable structures calculated by DFT alone. Dependences of bond energies (per atom) reflect the evolution of the segregation effect. The mass spectral abundances could be reasonably rationalized in terms of calculated stabilities of the cluster ions with respect to various dissociation channels.