Assessing diet in a university student population: a longitudinal food card transaction data approach.

Starting university is an important time with respect to dietary changes. This study reports a novel approach to assessing student diet by utilising student-level food transaction data to explore dietary patterns. First-year students living in catered accommodation at the University of Leeds (UK) received pre-credited food cards for use in university catering facilities. Food card transaction data were obtained for semester 1, 2016 and linked with student age and sex. k-Means cluster analysis was applied to the transaction data to identify clusters of food purchasing behaviours. Differences in demographic and behavioural characteristics across clusters were examined using χ2 tests. The semester was divided into three time periods to explore longitudinal changes in purchasing patterns. Seven dietary clusters were identified: 'Vegetarian', 'Omnivores', 'Dieters', 'Dish of the Day', 'Grab-and-Go', 'Carb Lovers' and 'Snackers'. There were statistically significant differences in sex (P < 0·001), with women dominating the Vegetarian and Dieters, age (P = 0·003), with over 20s representing a high proportion of the Omnivores and time of day of transactions (P < 0·001), with Dieters and Snackers purchasing least at breakfast. Many students (n 474, 60·4 %) changed dietary cluster across the semester. This study demonstrates that transactional data present a feasible method for dietary assessment, collecting detailed dietary information over time and at scale, while eliminating participant burden and possible bias from self-selection, observation and attrition. It revealed that student diets are complex and that simplistic measures of diet, focusing on narrow food groups in isolation, are unlikely to adequately capture dietary behaviours.

Feature analysis of ultrasound elastography image for quantitative assessment of cutaneous carcinoma.

BACKGROUND: To evaluate the feasibility of using quantitative texture features computed from high frequency ultrasound and ultrasound elastography (USE) images in the discrimination of benign from malignant skin lesions. METHODS: A commercial ultrasound system with a 14 MHz transducer was used to visualize skin lesions requiring biopsy on clinical evaluation. Patients were enrolled over a 6-month period and imaged prospectively by operators blind to the histopathologic diagnosis. Anatomic ultrasound and USE imaging of the skin lesions was performed using a 2-4 mm gel standoff pad before biopsy and histopathologic evaluation. The ElastoAnalysis software developed for the texture analysis of USE images was provided by Hitachi. The software computes thirteen texture features within a region of interest (ROI), which have demonstrated promise in diagnostic characterization of liver fibrosis staging and in quantitative elastography of breast cancer. This approach has not yet been studied in the quantitative assessment of skin cancer. Results were retrospectively compared to the histopathologic diagnosis and a diagnostic criteria with the goal of maximizing sensitivity was evaluated for each textural feature. RESULTS: Of the 37 lesions included, among 30 patients who participated, 12 lesions were malignant and 25 were benign. Eleven out of thirteen textural metrics computed by the software were useful in differentiating benign from malignant lesions with 100% sensitivity and specificities ranging from 28% to 85%. CONCLUSIONS: This feasibility study demonstrated that feature analysis of USE may be useful in quantitatively differentiating cancerous from benign primary solitary skin lesions prior to biopsy.

Interaction between cytokines and inflammatory cells in islet dysfunction, insulin resistance and vascular disease.

Inflammation is an established pathogenic player in insulin resistance, islet demise and atherosclerosis. The complex interactions between cytokines, immune cells and affected tissues result in sustained inflammation in diabetes and atherosclerosis. 12- and 15-lipoxygenase (LO), such as 12/15-LO, produces a variety of metabolites through peroxidation of fatty acids and potentially contributes to the complex molecular crosstalk at the site of inflammation. 12- and 15-LO pathways are frequently activated in tissues affected by diabetes and atherosclerosis including adipose tissue (AT), islets and the vasculature. Moreover, mice with whole body and tissue-specific knockout of 12/15-LO are protected against insulin resistance, hyperglycaemia and atherosclerosis supporting functional contribution of 12- and 15-LO pathways in diabetes and atherosclerosis. Recently, it has emerged that there is a temporal regulation of the particular isoforms of 12- and 15-LO in human AT and islets during the development of type 1 and type 2 diabetes and obesity. Analyses of tissues affected by diabetes and atherosclerosis also implied the roles of interleukin (IL)-12 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX-1) in islets and IL-17A in atherosclerosis. Future studies should aim to test the efficacy of inhibitions of these mediators for treatment of diabetes and atherosclerosis.

Progress Towards Using Linked Population-Based Data For Geohealth Research: Comparisons Of Aotearoa New Zealand And The United Kingdom.

Globally, geospatial concepts are becoming increasingly important in epidemiological and public health research. Individual level linked population-based data afford researchers with opportunities to undertake complex analyses unrivalled by other sources. However, there are significant challenges associated with using such data for impactful geohealth research. Issues range from extracting, linking and anonymising data, to the translation of findings into policy whilst working to often conflicting agendas of government and academia. Innovative organisational partnerships are therefore central to effective data use. To extend and develop existing collaborations between the institutions, in June 2019, authors from the Leeds Institute for Data Analytics and the Alan Turing Institute, London, visited the Geohealth Laboratory based at the University of Canterbury, New Zealand. This paper provides an overview of insight shared during a two-day workshop considering aspects of linked population-based data for impactful geohealth research. Specifically, we discuss both the collaborative partnership between New Zealand's Ministry of Health (MoH) and the University of Canterbury's GeoHealth Lab and novel infrastructure, and commercial partnerships enabled through the Leeds Institute for Data Analytics and the Alan Turing Institute in the UK. We consider the New Zealand Integrated Data Infrastructure as a case study approach to population-based linked health data and compare similar approaches taken by the UK towards integrated data infrastructures, including the ESRC Big Data Network centres, the UK Biobank, and longitudinal cohorts. We reflect on and compare the geohealth landscapes in New Zealand and the UK to set out recommendations and considerations for this rapidly evolving discipline.

De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features.

Loss-of-function mutations of MECP2 are responsible for Rett syndrome (RTT), an X-linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single-strand conformation analysis (SSCA) and multiplex ligation-dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X-chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation.

Accreditation of the PGD laboratory.

Accreditation according to an internationally recognized standard is increasingly acknowledged as the single most effective route to comprehensive laboratory quality assurance, and many countries are progressively moving towards compulsory accreditation of medical testing laboratories. The ESHRE PGD Consortium and some regulatory bodies recommend that all PGD laboratories should be accredited or working actively towards accreditation, according to the internationally recognized standard ISO 15189, 'Medical laboratories-Particular requirements for quality and competence'. ISO 15189 requires comprehensive quality assurance. Detailed management and technical requirements are defined in the two major chapters. The management requirements address quality management including the quality policy and manual, document control, non-conformities and corrective actions, continual improvement, auditing, management review, contracts, referrals and resolution of complaints. Technical requirements include personnel competence (both technical and medical), equipment, accommodation and environment, and pre-analytical, analytical and post-analytical processes. Emphasis is placed on the particular requirements of patient care: notably sample identification and traceability, test validation and interpretation and reporting of results. Quality indicators must be developed to monitor contributions to patient care and continual improvement. We discuss the implementation of ISO 15189 with a specific emphasis on the PGD laboratory, highlight elements of particular importance or difficulty and provide suggestions of effective and efficient ways to obtain accreditation. The focus is on the European environment although the principles are globally applicable.

The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening.

BACKGROUND: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. METHODS: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. CONCLUSIONS: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.

Surgical decision-making in infants with suspected UPJ obstruction: stakeholder perspectives.

INTRODUCTION: Although there are significant demographic and clinical variations in treatment decisions for infants with high-grade hydronephrosis concerning for ureteropelvic junction obstruction (UPJO), there has been little research on the roles of parents and surgeons in the surgical decision-making (DM) process. OBJECTIVE: The purpose of this study was to understand parents' and surgeons' perceived roles in the surgical DM process for infants with high-grade hydronephrosis. STUDY DESIGN: Semistructured interviews were conducted with pediatric urologists from three regionally diverse tertiary referral sites and parents of infants diagnosed and treated for unilateral Society for Fetal Urology grade 3 or 4 hydronephrosis at one tertiary pediatric urology practice. Purposive sampling was used to ensure adequate representation of parents based on treatment choice, patient gender, race/ethnicity, and distance from the practice. Survey domains included (1) discussions about diagnosis and treatment options, (2) factors guiding treatment choice, and (3) participants' role in the DM process. Transcribed data and field notes were analyzed using a team-based, inductive grounded theory qualitative approach. RESULTS: Thirteen physicians and 32 parents were interviewed between November 2016 and November 2017. Parents and surgeons agreed that the surgeon was best equipped to guide treatment decisions because of their clinical knowledge and experience. Parents reported that their trust in the surgeon was the primary factor in their decisions. Surgeons reported tailoring discussions with parents to not only educate them about treatment options but also to develop an ongoing relationship with parents. Both parents and surgeons reported being satisfied with their roles in the DM process. DISCUSSION: This study suggests that parental trust in the surgeon and surgeon recommendations drive DM. This may be due to a lack of explicit discussion of options or of parental values and preferences for care. Limited discussions may also impact parental understanding of risks and potential complications. These findings are similar to those of prior studies in adults and children considering elective surgery. CONCLUSIONS: In this study, parents and surgeons reported that surgeon recommendations, rather than parent preferences, guide treatment choices for infants with suspected UPJO. Both parents and surgeons are satisfied with a physician-driven approach to DM, suggesting that, in situations where the perceived risk is low and parental knowledge is limited, parents may find a physician-led approach beneficial. Data gleaned from this study will be used to inform future quantitative studies evaluating factors guiding surgeon recommendations for treatment and their associations with underlying treatment variation.

Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors.

Molecular analysis of F8 in Lebanese haemophilia A patients: novel mutations and phenotype-genotype correlation.

Haemophilia A (HA) is an X-linked recessive hereditary bleeding disorder affecting one in 5000 men, resulting from mutations in the F8 gene. Our objective was to identify the spectrum of mutations of the F8 gene in Lebanese patients, and to perform genotype/phenotype correlations. A group of 79 HA patients from 55 unrelated families was studied. Patients were screened for intron 22 and intron 1 inversion using PCR. In the absence of mutations in both introns, a dHPLC screening followed by a DNA sequencing of all coding regions was performed. When patients presented novel mutations, 150 control chromosomes were tested to exclude common polymorphisms. Large deletions were confirmed by MLPA technique. The mRNA was specifically studied whenever a splice site mutation was detected. In addition, studies of the putative biochemical function and FVIII 3D structures were conducted. Thirty-four mutations were identified in this study of which 21 were novel: 11 missense, two nonsense, two splice sites, five small deletions and one large deletion. Inhibitor found in three over 75 patients correlated with large deletion, intron 22 inversion, and nonsense mutations. We were able to identify all causative mutations in those HA patients. This knowledge represents a huge step for genetic counselling.

Mesoporous silicas impregnated with cobalt and nickel oxide nanoparticles and the growth of carbon nanotubes there from.

Metal oxide-based nanoparticles of cobalt or nickel were deposited inside the pores and on the surface of hexagonal mesoporous silicas by a direct synthesis technique using Pluronic P85 and P123 surfactants as structure directing agents with the appropriate metal phthalocyanine as a metal precursor. Metal loadings were between 0.4-3.2 wt.%. XPS studies showed that the initial form of the metal oxide nanoparticles were [CoO] and [NiO] respectively. Samples of these materials formed from the P85 surfactant and 3.0 wt.% were used to grow carbon nanotubes (CNTs) from acetylene feedstock in a catalytic chemical vapour deposition (CCVD) reactor at 800 degrees C. CNT growth appeared to be random and the CNTs had diameters ranging from < 10 to > 90 nm. Treatment of the metal impregnated silicas with nitric acid produced materials which, under the same CNT growth conditions, afforded more uniform CNTs with diameters between 5-15 nm. No significant loss in mesophase ordering was seen in the TEM, PXRD or nitrogen physisorption analysis of the acid washed samples. CNTs grown with cobalt impregnated silicas formed with the P123 surfactant had diameters in the range 15-25 nm. Raman spectroscopy of the CNT products showed the nanotubes were highly graphitised and of good quality.

Cytotoxic antibodies to cloned rat islet cells in serum of patients with diabetes mellitus.

We have found complement-dependent cytotoxic antibodies in the serum of 8 of 24 patients with insulin-dependent diabetes mellitus using a 51Cr cytotoxicity assay with monolayers of cloned rat islet cells (clones RINm 5F and RINm 14B). In contrast, complement-dependent cytotoxicity with 51Cr release greater than 24% was found with sera from 34 controls or from 5 patients with polyglandular failure without diabetes, and was present in only 1 serum our of 12 from patients with insulin-independent diabetes mellitus. The prevalence of antibodies appears to decrease with duration of insulin-dependent diabetes, and in one patient studied, cytotoxic antibodies were present at the time of diagnosis of diabetes. Cytotoxicity is independent of insulin synthesis, as evidenced by the linear correlation of cytotoxicity of sera for the insulin-producing clone RINm 5F and the somatostatin-producing clone RINm 14B. The present study identifies nonspecies-specific cytotoxic antibodies in the serum of patients with diabetes mellitus, and the assay used should facilitate studies of humoral immunity in the pathogenesis of diabetes mellitus.

Deletion of the fibrinogen [correction of fibrogen] alpha-chain gene (FGA) causes congenital afibrogenemia.

Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. Uncontrolled bleeding after birth from the umbilical cord is common, and spontaneous intracerebral bleeding and splenic rupture can occur throughout life. Patients respond well to fibrinogen replacement therapy, either prophylactically or on demand. Because the half-life of infused fibrinogen is essentially normal, the genetic defect is assumed to be at the level of synthesis, but no responsible locus has been identified. Preliminary studies using Southern blotting suggested that no gross structural changes of the fibrinogen genes were present in patients. We report the identification of causative mutations in a nonconsanguineous Swiss family with congenital afibrinogenemia. The four affected male individuals (two brothers and their two first cousins) have homozygous deletions of approximately 11 kb of the fibrinogen alpha-chain gene (FGA). Haplotype data suggest that these deletions occurred separately, on three distinct ancestral chromosomes, implying that the FGA region of the fibrinogen locus is susceptible to deletion by a common mechanism. Furthermore, our results demonstrate that humans, like mice, may be born without the capacity to synthesize functional fibrinogen.

Potential of FeAlCr intermetallics reinforced with nanoparticles as new biomaterials for medical devices.

Novel FeAlCr oxide dispersion strengthened intermetallics that are processed by powder metallurgy have been developed as potential biomaterials. The alloys exhibit a small grain size and a fine dispersion of yttria provides the material with a high yield strength and depending on the alloy composition good ductility (up to 5%). The biocompatibility of the alloy was assessed in comparison with commercial alumina. Saos-2 osteoblast-like cells were either challenged with mechanically alloyed particles, or seeded onto solid samples. Viability and proliferation of cells were substantially unaffected by the presence of a high concentration of particles (1 mg/mL). Solid samples of novel FeAlCr intermetallic have shown a good biocompatibility in vitro, often approaching the behavior of materials well known for their biological acceptance (e.g. alumina). It has been found that osteoblasts are able to produce ALP, a specific marker of cells with bone-forming activity. In this respect, ALUSI alloys hold the promise to be suitable substrate for bone integration. The finding of no cytotoxic effect in the presence of the alloy particles is a reliable proof of the absence of acute toxicity of the material.

The remarkable reaction of N2O with a binary component lanthanide oxide mixture.

The interaction of N2O with a Sm2O3-PrO(2-x) mixed oxide proceeds via the unexpected production of a new bulk phase that has been tenatively assigned to a new cis-hyponitrite compound.

Polymeric Based Therapeutic Delivery Systems Prepared Using Electrohydrodynamic Processes.

The development of therapeutic dosage (e.g. pharmaceutical) systems is an ongoing process which, in recent times has incorporated several emerging disciplines and themes at timely intervals. While the concepts surrounding dosage forms have developed and evolved, many polymeric excipients remain as the preferred choice of materials over existing counterparts, serving functions as matrix materials, coatings and providing other specific functional properties (e.g. adhesion, controlled release and mechanical properties). There have been, however, developments in the deployment of synthetic polymeric materials (e.g. polycaprolactone, poly lactic co-glycolic acid) when compared to naturally occurring materials (e.g. lactose, gelatin). Advances in pharmaceutical process technologies have also provided novel engineering platforms to develop a host of exciting structure based materials ranging from the nanometer to the macro scales. Some of these structure enabling technologies include spray drying, super critical processing, microfluidics and even wet chemical methods. More recently electrohydrodynamic (EHDA) engineering methods have emerged as robust technologies offering potential to fabricate a plethora of generic structures (e.g. particles, fibres, bubbles and pre-determined patterns) on a broad scale range. This review focuses on key developments using various EHDA technologies for the pharmaceutical and biomaterial remits when selecting synthetic and/or naturally occurring polymers as pharmaceutical (and therapeutic) excipients. In addition, the underlying EHDA process principles are discussed along with key parameters and variables (both materials and engineering). EHDA technologies are operational at ambient conditions and recent developments have also demonstrated their viability for large scale production. These are promising technologies which have potential in established (e.g. films, dressings and microparticles) and emerging scientific themes (e.g. nanomedicines and tissue engineering).

Mechanical properties and biocompatibility of the sputtered Ti doped hydroxyapatite.

The hydroxyapatite enriched with Ti were prepared as possible candidates for biomedical applications especially for implantable devices that are in direct contact to the bone. The hydroxyapatites with different Ti content were prepared by RF magnetron sputtering on Ti-6Al-4V alloy using pure hydroxyapatite and TiO2 targets. The content of Ti was modified by changing the RF power fed on TiO2 target. The XPS and FTIR analyses revealed the presence of hydroxyapatite structure. The hardness and elastic modulus of the hydroxyapatite were increased by Ti addition. After 5 days of culture, the cell viability of the Ti-6Al-4V was enhanced by depositing with undoped or doped hydroxyapatite. The Ti additions led to an increase in cell viability of hydroxyapatite, after 5 days of culture. The electron microscopy showed the presence of more cells on the surface of Ti-enriched hydroxyapatite than those observed on the surface of the uncoated alloys or undoped hydroxyapatite.

Differential sensitivity to beta-cell secretagogues in "early," type I diabetes mellitus.

The insulin secretory response to various beta-cell secretagogues was studied in four children (ages 11, 11, 12, and 10 yr) in "early" stages or remission of type I diabetes mellitus. One child was an anti-islet antibody positive monozygotic twin of a type I diabetic subject, two children had impaired glucose tolerance and elevated levels of Ia-positive T-cells, and the fourth was in remission (off insulin) of type I diabetes 6 mo after immunotherapy. The peak first-phase (0-10 min) insulin increment after intravenous (i.v.) glucose was negligible in each patient, whereas the peak responses to i.v. glucagon, tolbutamide, arginine, and oral glucose ranged between 10% and 43% of median responses in normal control subjects. The rank order of response to a variety of secretagogues was remarkably similar in all four subjects: i.v. arginine greater than i.v. glucagon greater than oral glucose greater than i.v. tolbutamide greater than i.v. glucose. These studies indicate that a "functional" beta-cell defect, namely a complete loss of response to i.v. glucose and a partial loss to other secretagogues, exists in type I diabetic patients before complete beta-cell destruction. This alteration in beta-cell responsiveness probably underlies our prior observation of slowly progressive loss of i.v.-glucose-induced insulin release in islet cell antibody-positive siblings to type I diabetic subjects.

Parental origin of the deletion 22q11.2 and brain development in velocardiofacial syndrome: a preliminary study.

BACKGROUND: As children with velocardiofacial syndrome (VCFS) develop, they are at increased risk for psychopathology; one third will eventually develop schizophrenia. Because VCFS and the concomitant symptomatology result from a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associations among genes, brain development, and behavior. The purpose of this study was to investigate the effect of the parental origin of the 22q11.2 microdeletion on the brain development of children and adolescents with VCFS. METHODS: Eighteen persons with VCFS and 18 normal control subjects were matched individually for age and sex. Results of DNA polymorphism analyses determined the parental origin of the deletion. Nine persons with VCFS had a deletion on the maternally derived chromosome 22; 9 persons, on the paternally derived chromosome 22. High-resolution magnetic resonance imaging scans were analyzed to provide quantitative measures of gray and white matter brain tissue. RESULTS: Total brain volume was approximately 11% smaller in the VCFS group than in controls. Comparisons between VCFS subgroups (maternal vs paternal microdeletion 22q11.2) indicated a significant 9% volumetric difference in total volume of cerebral gray matter (volume was greater in patients with paternal microdeletion) but not cerebral white matter. Significant age-related changes in gray matter were detected for subjects whose 22q11.2 deletion was on the maternal chromosome. CONCLUSIONS: Children and adolescents with VCFS experience major alterations in brain volumes. Significant reduction in gray matter development is attributable to presence of 22q11.2 microdeletion on the maternal chromosome.