Karak syndrome: a novel degenerative disorder of the basal ganglia and cerebellum

Two brothers are reported with early onset progressive cerebellar ataxia, dystonia, spasticity, and intellectual decline. • Neuroradiology showed cerebellar atrophy and features compatible with iron deposition in the putamen (including the “eye of the tiger sign”) and substantia nigra. • Diagnosis was compatible with pantothenate kinase associated neuropathy resulting from pantothenate kinase 2 mutation (PKAN due to PANK2) but linkage to PNAK2 was eliminated suggesting Karak syndrome to be a novel disorder. • The “eye of the tiger” sign has previously only been reported to occur in PKAN due to PKAN

Proactive risk assessment of vincristine use process in a teaching and referral hospital in Kenya

Background: The chemotherapy use process is considered as potentially risky for cancer patients due to its complex process, use of agents with narrow therapeutic indeces, multiple drug use and use of potentially toxic compounds adding to morbidity and mortality for patients with cancer. Vincristine, a "High Alert" medicine, has been associated with fatal but preventable medication errors. Objective: To determine hazards associated with vincristine use process by performing proactive risk assessments using Healthcare Failure Mode Effect Analysis (HFMEA). Methods: A multidisciplinary health team identified and evaluated potential failure modes based on vincristine use process flow diagram using a hazard scoring matrix in a leading referral hospital in Kenya treating patients with cancer. The hazard score matrix was based on the published literature. Failure modes were prioritized using decision tree analysis in which recommendations to counteract the risks were determined. Results: The processes evaluated were; prescribing, preparation and dispensing, transportation and storage, administration and monitoring of use. A total of 77 failure modes were identified over the 3 months period of the study, April to June 2017, of which 25 were classified as high risk. Thirteen were adequately covered by existing control measures while the other 12 required the development of mitigation strategies. Two of the 12 failure modes were single-point weaknesses. Conclusions: Multiple medication errors, some with serious consequences, can occur at each stage of the chemotherapy use process making it a high-risk process. HFMEA is a useful tool to identify improvements to medication safety and reduce patient harm. The HFMEA process brings together the multidisciplinary team involved in patient care in actively identifying potential failure modes and therefore owning the recommendations made. This is now being followed up

How toddlers' irritability and fearfulness relate to parenting : a longitudinal study conducted among Quebec families

Although child difficult temperament is a well‐known risk factor for parenting quality, few studies have focused on the association between specific temperament dimensions and parental behaviours. This study focused on negative emotionality, one of the best‐accepted dimensions of temperament, and its subdimensions of irritability and fearfulness. The aim of the present study was to evaluate the predictive value of irritability and fearfulness at 17 months upon parenting practices (involvement, coercion, and overprotection) at 29 months, beyond the influence of other well‐known risk factors (e.g., socio‐economic status and maternal depression). The study used data from the Quebec Longitudinal Study of Child Development, a longitudinal study conducted upon 1,829 families from Quebec (Canada), using self‐report questionnaires and medical files. Structural equation modelling identified irritability as a predictor of coercion, an externally controlling practice, whereas fearfulness predicted overprotection, an internally controlling practice. No significant associations were found after modelling between dimensions of negative emotionality and involvement. These results underline how certain aspects of child temperament may differentially “pull for control” and lead parents to act in a certain way, which may thwart young children's development and need for autonomy. Highlights This article investigates the associations between negative emotionality (i.e., irritability and fearfulness) and parenting (i.e., involvement, coercion, and overprotection). Structural equation modelling was used on data collected during a longitudinal study with a representative sample of 2,223 families. Each dimension of negative emotionality was associated to a different form of controlling parenting 1 year later (i.e., irritability with coercion and fearfulness with overprotection)

Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

Background Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. Methods We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (\u3c32 weeks gestation). Respiratory distress scores were developed to examine the clinical severity of HMPV infections. Demographic and clinical variables were obtained from reviewing electronic medical records. Results A total of 571 preschool children were identified using polymerase chain reaction-confirmed viral respiratory tract infection during the study period. HMPV was identified as a causative organism in 63 cases (11%). Fifty–eight (n = 58) preschool-age children with HMPV infection were included in this study after excluding those with significant comorbidities. Our data demonstrated that 32.7% of children admitted with HMPV had a history of severe prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma. Conclusion Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations

Phenotypical Characterization of Human Rhinovirus Infections in Severely Premature Children

Background: Human Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV. Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤ 3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve (hypoxemia and tachypnea) in young children with HRV infections. Demographic and clinical variables were obtained from reviewing electronic medical records (EMR). Results: This study included a total of 205 children; 71% of these children were born full-term (\u3e 37 weeks gestation), 10% preterm (32–37 weeks) and 19% severely premature (\u3c 32 weeks). Our results demonstrated that: 1) HRV infections in the first 3 years of life were associated with higher overall respiratory distress scores in severely premature children relative to children born preterm or full-term; 2) HRV-infected severely premature children ≤ 3 years old were more likely to have lower airway obstruction than HRV-infected children born preterm or full-term; and 3) other clinical signs of respiratory distress such as tachypnea and hypoxemia were not more common in severely premature than in preterm and full-term children during an HRV infection Conclusions: Our results indicate that HRV infections in severely premature children are associated with lower airway obstruction rather than hypoxemia or tachypnea. The latter suggests that enhanced airway reactivity is the underlying mechanism for the increased susceptibility to HRV in severely premature children. Longitudinal studies are needed to understand why premature babies develop airway hyper-reactivity to HRV and the long-term effects of early HRV infection in this population

Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

Abstract: Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children). Sixty-seven percent of these hospitalizations occurred in children born full-term (\u3e 37 weeks), 12% in preterm (32–37 weeks) and 21% in severely premature children (\u3c 32 weeks). The most common viruses identified were rhinovirus (RV; 60%) and respiratory syncytial virus (RSV; 17%). Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life

Short-wavelength four wave mixing experiments using single and two-color schemes at FERMI

The development of ultra-bright extreme ultraviolet (EUV) and X-ray free electron laser (FEL) sources has enabled the extension of wave-mixing approaches into the short wavelength regime. Such a class of experiments relies upon nonlinear interactions among multiple light pulses offering a unique tool for exploring the dynamics of ultrafast processes and correlations between selected excitations at relevant length and time scales adding elemental and site selectivity as well. Besides the availability of a suitable photon source, the implementation of wave mixing methodology requires efforts in developing the instrumental set-up. We have realized at the FERMI FEL two dedicated set-ups to handle multiple FEL beams with preselected parameters in a non-collinear fashion and control their interaction sequence at the target. These unique apparatuses, combined with the exceptional characteristics of the seeded FERMI FEL, have allowed us to make the first steps into this field and further advances are foreseen in the near future

The PHIN photoinjector for the CTF3 Drive beam

A new photoinjector for the CTF3 drive beam has been designed and is now being constructed by a collaboration among LAL, CCLRC and CERN within PHIN, the second Joint Research Activity of CARE. The photoinjector will provide a train of 2332 pulses at 1.5 GHz with a complex timing structure (sub-trains of 212 pulses spaced from one another by 333 ps or 999 ps) to allow the frequency multiplication scheme, which is one of the features of CLIC, to be tested in CTF3. Each pulse of 2.33 nC will be emitted by a Cs2Te photocathode deposited by a co-evaporation process to allow high quantum efficiency in operation (>3% for a minimum of 40 h). The 3 GHz, 2 1/2 cell RF gun has a 2 port coupler to minimize emittance growth due to asymmetric fields, racetrack profile of the irises and two solenoids to keep the emittance at the output below 20 p.mm.mrad. The laser has to survive very high average powers both within the pulse train (15 kW) and overall (200 W before pulse slicing). Challenging targets are also for amplitude stability (<0.25% rms) and time jitter from pulse to pulse (<1ps rms). An offline test in a dedicated line is foreseen at CERN in 2007

Ultra-Low Threshold cw Lasing in Tensile Strained GeSn Microdisk Cavities

GeSn is proven as a good candidate to achieve CMOS-compatible laser sources on silicon. Lasing demonstrations in this alloy were based on directness of the band structure, this directness being increased with increasing the Sn content above 8 at.%. These past few years the research were consequently focused on incorporating the highest Sn content as possible to achieve high directness and high temperature laser operation. This unfortunately results is increased threshold. In this contribution we discuss the advantages in combining tensile strain engineering with lower Sn content alloys. This approach is motivated by the higher material quality in lower Sn content. The case with Sn content as small as 5.4 at.% Sn will be discussed. The alloy is initially compressively strained, and exhibits an indirect band gap that is turned to direct by applying tensile strain. A specific technology based on transfer On Insulator stressor layer on metal was developed to address strain engineering, thermal cooling and defective interface with the Ge-VS. This led to lasing in Ge0.95Sn0.05 microdisk cavities with dramatically reduced thresholds, by two order of magnitude, as compared to the case with high Sn alloys and as consequence enables cw operation