The role of rhinovirus infections in young children with cystic fibrosis.

Rhinovirus (RV) is an important virus in children with chronic respiratory conditions such as asthma; however, little is known about its role in CF. Our aim was to examine the prevalence and clinical impact of different RV species in young children with CF. We collected clinical data and nasal swabs on patients at home and in the hospital setting. Parents filled out symptom diaries and collected nasal swabs when their children were symptomatic and asymptomatic. A novel RV typing PCR assay was used to determine the RV species present. We collected 55 nasal swab samples from ten preschool CF patients over a six month period. The quality of parent collected samples at home was sufficient for PCR analysis. RV was the most common virus detected in young children with CF. There was no difference in the frequency of RV species between symptomatic and asymptomatic subjects. However, parental home-sampling is an acceptable and feasible approach to monitoring young children with CF.

Plasma microRNA levels in male and female children with cystic fibrosis.

A gender gap exists in cystic fibrosis (CF). Here we investigate whether plasma microRNA expression profiles differ between the sexes in CF children. MicroRNA expression was quantified in paediatric CF plasma (n = 12; six females; Age range:1-6; Median Age: 3; 9 p.Phe508del homo- or heterozygotes) using TaqMan OpenArray Human miRNA Panels. Principal component analysis indicated differences in male versus female miRNA profiles. The miRNA array analysis revealed two miRNAs which were significantly increased in the female samples (miR-885-5p; fold change (FC):5.07, adjusted p value: 0.026 and miR-193a-5p; FC:2.6, adjusted p value: 0.031), although only miR-885-5p was validated as increased in females using specific qPCR assay (p < 0.0001). Gene ontology analysis of miR-885-5p validated targets identified cell migration, motility and fibrosis as processes potentially affected, with RAC1-mediated signalling featuring significantly. There is a significant increase in miR-885-5p in plasma of females versus males with CF under six years of age.

The Microalbuminuria Education Medication and Optimisation (MEMO) study: 4 years follow-up of multifactorial intervention in high-risk individuals with type 2 diabetes.

AIMS: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P < 0.001), diastolic BP (-2.9 mmHg, 95% CI -5.4, -0.3; P = 0.026), cholesterol (-0.3 mmol/l, 95% CI -0.52,-0.12; P = 0.002), and 10-year coronary heart disease (-5.3, 95% CI -8.2,-2.3; P < 0.001) and stroke risk (-4.4, 95% CI -7.5, -1.3; P < 0.001). CONCLUSION: Multifactorial intervention with structured diabetes self-management education compared with usual diabetes care has benefits for cardio-metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes.

The Prevalence of Pseudomonas Aeruginosa Infection Over a Ten-Year Period in Children with Cystic Fibrosis

Background Pseudomonas aeruginosa (PA) infection is associated with an increased morbidity and adverse prognosis in children with Cystic Fibrosis(CF). The aim of the study was to evaluate the prevalence and characteristics of PA over a ten year period at a single paediatric tertiary referral centre in Ireland. Methods This was a retrospective cross-sectional study. Patient's case notes, microbiology laboratory results and CF Registry of Ireland(CFRI) data were used to collect the data. Results The overall chronic PA infection prevalence was 28.1%(45/160) in 2004 and 21.3%(35/164) in 2014. In 2004, 54/160(33.8%) patients were never infected with PA, 27/160(16.9%) were free for 12 months and 34/160(21.3%) were intermittently infected. In 2014; 80/164(49%) patients, 38/164(23.2%) and 11/164(6.7%) were never infected, free for 12 months and intermittently infected respectively. Conclusion There has been a decline in the overall prevalence of PA infection and a change in the pattern of prevalence over the last decade at our Centre.

Inductively coupled 30 T magnetic field platform for magnetized high-energy-density plasma studies.

A pulsed high magnetic field device based on the inductively coupled coil concept [D. H. Barnak et al., Rev. Sci. Instrum. 89, 033501 (2018)] is described. The device can be used for studying magnetized high-energy-density plasma and is capable of producing a pulsed magnetic field of 30 T inside a single-turn coil with an inner diameter of 6.5 mm and a length of 6.3 mm. The magnetic field is created by discharging a high-voltage capacitor through a multi-turn solenoid, which is inductively coupled to a small single-turn coil. The solenoid electric current pulse of tens of kA and a duration of several µs is inductively transformed to hundreds of kA in the single-turn coil, thus enabling a high magnetic field. Unlike directly driven single-turn systems that require a high-current and low-inductive power supply, the inductively coupled system operates using a relatively low-current power supply with very relaxed requirements for its inductance. This arrangement significantly simplifies the design of the power supply and also makes it possible to place the power supply at a significant distance from the coil. In addition, the device is designed to contain possible wire debris, which makes it attractive for debris-sensitive applications.

Nondestructive X-ray diffraction measurement of warpage in silicon dies embedded in integrated circuit packages.

Transmission X-ray diffraction imaging in both monochromatic and white beam section mode has been used to measure quantitatively the displacement and warpage stress in encapsulated silicon devices. The displacement dependence with position on the die was found to agree well with that predicted from a simple model of warpage stress. For uQFN microcontrollers, glued only at the corners, the measured misorientation contours are consistent with those predicted using finite element analysis. The absolute displacement, measured along a line through the die centre, was comparable to that reported independently by high-resolution X-ray diffraction and optical interferometry of similar samples. It is demonstrated that the precision is greater than the spread of values found in randomly selected batches of commercial devices, making the techniques viable for industrial inspection purposes.

Simultaneous depth-profiling of electrical and elemental properties of ion-implanted arsenic in silicon by combining secondary-ion mass spectrometry with resistivity measurements.

A method is proposed to extract the electrical data for surface doping profiles of semiconductors in unison with the chemical profile acquired by secondary-ion mass spectrometry (SIMS)-a method we call SIMSAR (secondary-ion mass spectrometry and resistivity). The SIMSAR approach utilizes the inherent sputtering process of SIMS, combined with sequential four-point van der Pauw resistivity measurements, to surmise the active doping profile as a function of depth. The technique is demonstrated for the case of ion-implanted arsenic doping profiles in silicon. Complications of the method are identified, explained, and corrections for these are given. While several techniques already exist for chemical dopant profiling and numerous for electrical profiling, since there is no technique which can measure both electrical and chemical profiles in parallel, SIMSAR has significant promise as an extension of the conventional dynamic SIMS technique, particularly for applications in the semiconductor industry.

A secretory leukocyte protease inhibitor variant with improved activity against lung infection.

Secretory leukocyte protease inhibitor (SLPI) is an important respiratory tract host defense protein, which is proteolytically inactivated by excessive neutrophil elastase (NE) during chronic Pseudomonas infection in the cystic fibrosis (CF) lung. We generated two putative NE-resistant variants of SLPI by site-directed mutagenesis, SLPI-A16G and SLPI-S15G-A16G, with a view to improving SLPI's proteolytic stability. Both variants showed enhanced resistance to degradation in the presence of excess NE as well as CF patient sputum compared with SLPI-wild type (SLPI-WT). The ability of both variants to bind bacterial lipopolysaccharides and interact with nuclear factor-κB DNA binding sites was also preserved. Finally, we demonstrate increased anti-inflammatory activity of the SLPI-A16G protein compared with SLPI-WT in a murine model of pulmonary Pseudomonas infection. This study demonstrates the increased stability of these SLPI variants compared with SLPI-WT and their therapeutic potential as a putative anti-inflammatory treatment for CF lung disease.

Local strain and defects in silicon wafers due to nanoindentation revealed by full-field X-ray microdiffraction imaging.

Quantitative characterization of local strain in silicon wafers is critical in view of issues such as wafer handling during manufacturing and strain engineering. In this work, full-field X-ray microdiffraction imaging using synchrotron radiation is employed to investigate the long-range distribution of strain fields in silicon wafers induced by indents under different conditions in order to simulate wafer fabrication damage. The technique provides a detailed quantitative mapping of strain and defect characterization at the micrometer spatial resolution and holds some advantages over conventional methods.

Diagnosis and treatment of sleep related breathing disorders in children: 2007 to 2011.

Sleep related breathing disorders (SRBD) have historically been under-recognised and under-treated. Obstructive sleep apnoea (OSA) affects approximately 3% of children. In line with the increased recognition of SRBD there has been an increase in demand for diagnostic services. We determined the awareness of SRBD amongst Irish paediatricians, examined the provision of sleep services to children throughout the country between 2007 and 2011 and audited diagnostic sleep services in a tertiary centre in 2011. Amongst respondents there was an awareness of SRBD but a poor understanding of diagnostic evaluation with 31/46 (67) referring to inappropriate services. There has been a sharp increase in both diagnostic sleep tests (433-1793 [414]) and in the use of non-invasive ventilation (NIV) (31-186 [627]) for treatment of SRBD between 2007 and 2011. Paediatric sleep services are organized in an ad-hoc manner nationally with significant service variation. The use of domiciliary overnight oximetry reduced the requirement for more formal polysomnography by 70%.

Influence of substrate metal alloy type on the properties of hydroxyapatite coatings deposited using a novel ambient temperature deposition technique.

Hydroxyapatite (HA) coatings are applied widely to enhance the level of osteointegration onto orthopedic implants. Atmospheric plasma spray (APS) is typically used for the deposition of these coatings; however, HA crystalline changes regularly occur during this high-thermal process. This article reports on the evaluation of a novel low-temperature (<47°C) HA deposition technique, called CoBlast, for the application of crystalline HA coatings. To-date, reports on the CoBlast technique have been limited to titanium alloy substrates. This study addresses the suitability of the CoBlast technique for the deposition of HA coatings on a number of alternative metal alloys utilized in the fabrication of orthopedic devices. In addition to titanium grade 5, both cobalt chromium and stainless steel 316 were investigated. In this study, HA coatings were deposited using both the CoBlast and the plasma sprayed techniques, and the resultant HA coating and substrate properties were evaluated and compared. The CoBlast-deposited HA coatings were found to present similar surface morphologies, interfacial properties, and composition irrespective of the substrate alloy type. Coating thickness however displayed some variation with the substrate alloy, ranging from 2.0 to 3.0 µm. This perhaps is associated with the electronegativity of the metal alloys. The APS-treated samples exhibited evidence of both coating, and significantly, substrate phase alterations for two metal alloys; titanium grade 5 and cobalt chrome. Conversely, the CoBlast-processed samples exhibited no phase changes in the substrates after depositions. The APS alterations were attributed to the brief, but high-intensity temperatures experienced during processing.

Soft x-ray spectroscopic investigation of Zn doped CuCl produced by pulsed dc magnetron sputtering.

We report on a systematic investigation of the electronic properties of UV-light emitting Zn doped CuCl thin films implemented using near edge x-ray absorption fine structures (NEXAFS) and high-resolution x-ray photoemission spectroscopy. A clear shift of the valence band maximum towards higher binding energy by 0.2 ± 0.1 eV was observed in Zn doped CuCl as compared to undoped CuCl. This shift is in correlation with the increase in conductivity measured by the Hall effect measurements. A decrease in the optical band gap of CuCl film is also observed as a function of Zn doping. The profound changes in the full width at half maximum and the gradual disappearance of satellite features of Cu 2p core level photoemission as a function of Zn dopant are attributed to the reduced presence of the surface layer of Cu(2+) species with d(9) configuration in the doped films. These investigations help us to understand the doping mechanisms and underlying physics. The reduced presence of the Cu(2+) related surface layer as a function of Zn doping is also verified using NEXAFS.

Hemoptysis from bronchial varices associated with pulmonary vein stenosis: role of surgical repair.

We present the case of a 6-year-old child who presented with an episode of life threatening hemoptysis. Investigations revealed multiple areas of endobronchial varices and abnormal pleural vessels as well as severe left pulmonary vein stenosis and an atrial septal defect (ASD). After extensive work up and consultation he underwent repair of the left pulmonary vein using a sutureless technique and ASD closure. This resulted in a marked improvement in the appearances of the left lung. The bronchial varices in the right lung remain unchanged. No further hemoptysis has occurred and the child continues to be monitored.

Ectopic prolactin secretion secondary to an ovarian tumour.

UNLABELLED: Ectopic hormone secretion is a well-recognised phenomenon; however, ectopic prolactin secretion is exceptionally rare. Hoffman and colleagues reported the first ever well-documented case of ectopic prolactin secretion secondary to a gonadoblastoma. We report a lady who presented with galactorrhoea and a large ovarian tumour that was found to secrete high levels of prolactin. LEARNING POINTS: Aim of this case report is to highlight the occurrence of this condition.Lack of awareness can often lead to a diagnostic conundrum.

Association of cardiac and non-cardiac chronic disease comorbidity on glycaemic control in a multi-ethnic population with type 1 and type 2 diabetes.

AIMS: To determine the prevalence of chronic disease comorbidity in south Asians (SAs) and white Europeans (WEs) with diabetes and to quantify the relationship of cardiac disease comorbidity (CDCM) and non-cardiac disease comorbidity (NCCM) to glycaemic control in SAs and WEs with type 1 and type 2 diabetes mellitus. METHODS: A cross-sectional study using a database of patients of SA (25.5%) and WE (74.5%) origin attending a specialist diabetes clinic in the UK between 2003 and 2005 (n=5664). RESULTS: The prevalence of SAs and WEs with type 1 diabetes was 12% and 88%, respectively; for those with type 2 diabetes the prevalence was 30% and 70%, respectively. Overall, the prevalence of comorbidity in people with type 1 diabetes was 25.5% and with type 2 diabetes was 47%. NCCM was more prevalent in WEs than SAs (17.6% vs 12.8%, p<0.001). In type 2 diabetes, the prevalence of suboptimal glycaemic control was significantly greater in SAs compared to WEs with NCCM and CDCM (79% vs 62%, p<0.001; 78% vs 65%, p<0.001, respectively). SAs with type 2 diabetes and comorbidity had excess odds of suboptimal glycaemic control compared to WEs: OR 2.27 (95% CI 1.50 to 3.43) for those with NCCM and OR 1.91 (95% CI 1.49 to 2.44) for those with CDCM. CONCLUSIONS: The prevalence of CDCM is higher in SAs compared to WEs with type 2 diabetes, whereas the prevalence of NCCM is higher in WEs compared to SAs. Taking into account comorbidities, SAs (compared to WEs) with type 2 diabetes had an excess risk of having HbA1c ≥7% ranging from 1.86- to 2.27-fold. Further research is needed to identify the reasons for unfavourable metabolic conditions in SAs and also develop and evaluate interventions.

Vitamin D receptor agonists inhibit pro-inflammatory cytokine production from the respiratory epithelium in cystic fibrosis.

BACKGROUND: 1,25-Dihydroxycholecalciferol (1,25(OH)(2)D(3)) has been shown to mitigate epithelial inflammatory responses after antigen exposure. Patients with cystic fibrosis (CF) are at particular risk for vitamin D deficiency. This may contribute to the exaggerated inflammatory response to pulmonary infection in CF. METHODS: CF respiratory epithelial cell lines were exposed to Pseudomonas aeruginosa lipopolysaccharide (LPS) and Pseudomonas conditioned medium (PCM) in the presence or absence of 1,25(OH)(2)D(3) or a range of vitamin D receptor (VDR) agonists. Levels of IL-6 and IL-8 were measured in cell supernatants, and cellular total and phosphorylated IκBα were determined. Levels of human cathelicidin antimicrobial peptide (hCAP18) mRNA and protein were measured in cells after treatment with 1,25(OH)(2)D(3). RESULTS: Pretreatment with 1,25(OH)(2)D(3) was associated with significant reductions in IL-6 and IL-8 protein secretion after antigen exposure, a finding reproduced with a range of low calcaemic VDR agonists. 1,25(OH)(2)D(3) treatment led to a decrease in IκBα phosphorylation and increased total cellular IκBα. Treatment with 1,25(OH)(2)D(3) was associated with an increase in hCAP18/LL-37 mRNA and protein levels. CONCLUSIONS: Both 1,25(OH)(2)D(3) and other VDR agonists significantly reduce the pro-inflammatory response to antigen challenge in CF airway epithelial cells. VDR agonists have significant therapeutic potential in CF.

Multifactorial intervention in individuals with type 2 diabetes and microalbuminuria: the Microalbuminuria Education and Medication Optimisation (MEMO) study.

AIMS: To determine whether tighter cardiovascular risk factor control with structured education in individuals with type 2 diabetes (T2DM) and microalbuminuria benefits cardiovascular risk factors. METHODS: Participants from a multiethnic population, recruited from primary care and specialist clinics were randomised to intensive intervention with structured patient (DESMOND model) education (n=94) or usual care by own health professional (n=95). PRIMARY OUTCOME: change in HbA1c at 18months. SECONDARY OUTCOMES: changes in blood pressure (BP), cholesterol, albuminuria, proportion reaching risk factor targets, modelled cardiovascular risk scores. RESULTS: Mean (SD) age and diabetes duration of participants were 61.5 (10.5) and 11.5 (9.3) years, respectively. At 18months, intensive intervention showed significant improvements in HbA1c (7.1(1.0) vs. 7.8(1.4)%, p<0.0001), systolic BP (129(16) vs. 139(17) mmHg, p<0.0001), diastolic BP (70(11) vs. 76(12) mmHg, p<0.001), total cholesterol (3.7(0.8) vs. 4.1(0.9) mmol/l, p=0.001). Moderate and severe hypoglycaemia was 11.2 vs. 29.0%; p=0.001 and 0 vs. 6.3%; p=0.07, respectively. More intensive participants achieved ≥3 risk factor targets with greater reductions in cardiovascular risk scores. CONCLUSIONS: Intensive intervention showed greater improvements in metabolic control and cardiovascular risk profile with lower rates of moderate and severe hypoglycaemia. Intensive glycaemic interventions should be underpinned by structured education promoting self-management in T2DM.