A novel 11 base pair deletion in KMT2C resulting in Kleefstra syndrome 2.

BACKGROUND: Haploinsufficiency of the Lysine Methyltransferase 2C (KMT2C) gene results in the autosomal dominant disorder, Kleefstra syndrome 2. It is an extremely rare neurodevelopmental condition, with 14 previous reports describing varied clinical manifestations including dysmorphic features, delayed psychomotor development and delayed growth. METHODS: Here, we describe a female with global developmental delay, attention deficit disorder, dyspraxia, short stature and subtle non-specific dysmorphic features. To identify causative mutations, whole exome sequencing was performed on the proband and her younger brother with discrete clinical presentation. RESULTS: Whole exome sequencing identified a novel de novo heterozygous 11 bp deletion in KMT2C (c.1759_1769del), resulting in a frameshift mutation and early termination of the protein (p.Gln587SerfsTer7). This variant is the second-most N-terminal reported mutation, located 4171 amino acids upstream of the critical enzymatically active SET domain (required for chromatin modification and histone methylation). CONCLUSION: The majority of the other reported mutations are frameshift mutations upstream of the SET domain and are predicted to result in protein truncation. It is thought that truncation of the SET domain, results functionally in an inability to modify chromatin through histone methylation. This report expands the clinical and genetic characterisation of Kleefstra syndrome 2.

CyberKnife Xsight versus fiducial-based target-tracking: a novel 3D dosimetric comparison in a dynamic phantom.

BACKGROUND: The CyberKnife Xsight lung-tracking system (XLTS) provides an alternative to fiducial-based target-tracking systems (FTTS) for non-small-cell lung cancer (NSCLC) patients without invasive fiducial insertion procedures. This study provides a method for 3D independent dosimetric verification of the accuracy of the FTTS compared to the XLTS without relying on log-files generated by the CyberKnife system. METHODS: A respiratory motion trace was taken from a 4D-CT of a real lung cancer patient and applied to a modified QUASAR™ respiratory motion phantom. A novel approach to 3D dosimetry was developed using Gafchromic EBT3 film, allowing the 3D dose distribution delivered to the moving phantom to be reconstructed. Treatments were planned using the recommended margins for one and three fiducial markers and XLTS 2-view, 1-view and 0-view target-tracking modalities. The dose delivery accuracy was analysed by comparing the reconstructed dose distributions to the planned dose distributions using gamma index analysis. RESULTS: For the 3%/2 mm gamma criterion, gamma passing rates up to 99.37% were observed for the static deliveries. The 3-fiducial and 1-fiducial-based deliveries exhibited passing rates of 93.74% and 97.82%, respectively, in the absence of target rotation. When target rotation was considered, the passing rate for 1-fiducial tracking degraded to 91.24%. The passing rates observed for XLTS 2-view, 1-view and 0-view target-tracking were 92.78%, 96.22% and 76.08%, respectively. CONCLUSIONS: Except for the XLTS 0-view, the dosimetric accuracy of the XLTS was comparable to the FTTS under equivalent treatment conditions. This study gives us further confidence in the CyberKnife XLTS and FTTS systems.

Comparison of conventional versus customised Eurosil-4 Pink bolus for radiotherapy of the chest wall.

INTRODUCTION: In radiotherapy, the presence of air gaps near a tumour can lead to underdose to the tumour. In this study, the impact of air gaps on dose to the surface was evaluated. 3D-printing was used to construct a Eurosil-4 Pink bolus customised to the patient and its dosimetric properties were compared with that of Paraffin wax bolus. METHODS: Surface dose was measured for flat sheets of Eurosil-4 Pink bolus with different thicknesses. Different air gap thicknesses were inserted between the bolus and the surface, and dose was measured for each air gap using 10 cm × 10 cm fields. This was repeated with the effective field size calculated from the patient plan. Surface dose was measured for varying angles of incidence. A customised chest phantom was used to compare dose for two customised Eurosil-4 Pink boluses, and commonly used Paraffin wax bolus. RESULTS: The surface dose was found to be highest for 1.1 cm thick bolus. The decrease in surface dose for the Eurosil-4 Pink bolus was minimal for the 10 cm × 10 cm field, but higher for the effective field size and larger angles of incidence. For instance, the dose was reduced by 6.2% as a result of 1 cm air gap for the effective field size and 60 degree angle of incidence. The doses measured using Gafchromic film under the customised Eurosil-4 Pink boluses were similar to that of the Paraffin wax bolus, and higher than prescribed dose. CONCLUSIONS: The impact of air gaps can be significant for small field sizes and oblique beams. A customised Eurosil-4 Pink bolus has promising physical and dosimetric properties to ensure sufficient dose to the tumour, even for treatments where larger impact of air gaps is suspected.

They Told Me "This Isn't a Hotel": Young People's Experiences and Perceptions of Care When Presenting to the Emergency Department with Suicide-Related Behaviour.

In Australia, the number of young people presenting to the emergency department with mental health concerns, in particular, suicidal behaviour (defined here as suicidal ideation, thoughts, intent and attempts) is increasing. Little is known about the experiences of Australian young people who present to hospital emergency departments with suicidal behaviour. In this qualitative study, we conducted a series of focus groups with 55 young people aged 16-25 years, with a view to developing a framework for youth suicide prevention for Western Australia. The data were analysed using a general inductive analysis approach. We explored the experiences and perceptions of the care and management of 35 young people presenting to Western Australian hospital emergency departments. Participants described a range of negative experiences relating to the emergency department environment, staff attitudes and their treatment by staff. We argue that adapting ED practices and approaches to young people presenting with suicidal thoughts and behaviours based on these findings will result in lower rates of repeated presentations and admissions to hospital and lower rates of suicide attempts and deaths by suicide.

Investigation of the effects of spinal surgical implants on radiotherapy dosimetry: A study of 3D printed phantoms.

PURPOSE: The use of three-dimensional (3D) printing to develop custom phantoms for dosimetric studies in radiotherapy is increasing. The process allows production of phantoms designed to evaluated specific geometries, patients, or patient groups with a defining feature. The ability to print bone-equivalent phantoms has, however, proved challenging. The purpose of this work was to 3D print a series of three similar spine phantoms containing no surgical implants, implants made of titanium, and implants made of carbon fiber, for future dosimetric and imaging studies. Phantoms were evaluated for (a) tissue and bone equivalence, (b) geometric accuracy compared to design, and (c) similarity to one another. METHODS: Sample blocks of PLA, HIPS, and StoneFil PLA-concrete with different infill densities were printed to evaluate tissue and bone equivalence. The samples were used to develop CT to physical (PD) and effective relative electron density (REDeff ) conversion curves and define the settings for printing the phantoms. CT scans of the printed phantoms were obtained to assess the geometry and densities achieved. Mean distance to agreement (MDA) and DICE coefficient (DSC) values were calculated between contours defining the different materials, obtained from design and like phantom modules. HU values were used to determine PD and REDeff and subsequently evaluate tissue and bone equivalence. RESULTS: Sample objects showed linear relationships between HU and both PD and REDeff for both PLA and StoneFil. The PD and REDeff of the objects calculated using clinical CT conversion curves were not accurate and custom conversion curves were required. PLA printed with 90% infill density was found to have a PD of 1.11 ± 0.03 g.cm-3 and REDeff of 1.04 ± 0.02 and selected for tissue- equivalent phantom elements. StoneFil printed with 100% infill density showed a PD of 1.35 ± 0.03 g.cm-3 and REDeff of 1.24 ± 0.04 and was selected for bone-equivalent elements. Upon evaluation of the final phantoms, the PLA elements displayed PD in the range of 1.10 ± 0.03 g.cm-3 -1.13 ± 0.03 g.cm-3 and REDeff in the range of 1.02 ± 0.03-1.06 ± 0.03. The StoneFil elements showed PD in the range of 1.43 ± 0.04 g.cm-3 -1.46 ± 0.04 g.cm-3 and REDeff in the range of 1.31 ± 0.04-1.33 ± 0.04. The PLA phantom elements were shown to have MDA of ≤1.00 mm and DSC of ≥0.95 compared to design, and ≤0.48 mm and ≥0.91 compared like modules. The StoneFil elements displayed MDA values of ≤0.44 mm and DSC of ≥0.98 compared to design and ≤0.43 mm and ≥0.92 compared like modules. CONCLUSIONS: Phantoms which were radiologically equivalent to tissue and bone were produced with a high level of similarity to design and even higher level of similarity of one another. When used in conjunction with the derived CT to PD or REDeff conversion curves they are suitable for evaluating the effects of spinal surgical implants of varying material of construction.

Homelessness youth and mental health service utilization: A long-term follow-up study.

BACKGROUND: There is currently an incomplete picture of the long-term impact of homelessness on youth with mental health issues. There are also questions regarding homelessness as a predictor of mental health re-admissions. AIMS: To examine the mental health service presentation profile of young people affected by homelessness and mental health issues. METHODS: A retrospective analysis was conducted of the medical records of homeless (n = 29) and non-homeless (n = 32) youth who attended the YouthLink specialist mental health service in 2010. We tracked their pattern of mental health service admissions at five time points during a total period of 10 years, including 2 years prior to, and up to 8 years following the YouthLink presentation. A regression analysis was used to examine factors hypothesized to contribute to mental health re-admissions. RESULTS: Homeless youth had significantly more frequent presentations to inpatient and outpatient mental health services, and emergency departments for mental health reasons. They were 11 times more likely to be re-admitted to a mental health inpatient ward than non-homeless youth. Prior hospital admission was an independent predictor, increasing by a factor of 2.2 for every inpatient admission. CONCLUSION: The impact of homelessness on mental health issues is enduring, and is a long-term predictor of hospital re-admission.

Intensive community treatment and support "Youth Wraparound" service in Western Australia: A case and feasibility study.

BACKGROUND: Multiple services are often needed to address the needs of young people with complex emotional or behavioural needs. The Youth Wraparound model of service aims to provide all health and supportive services from one coordinating agency. While this has been researched overseas, there are currently few examples of this described in the Australian psychiatric context. AIM: To document the implementation and evaluation of a Youth Wraparound service which was provided to a young person with exceptionally complex and challenging needs for 6 months. A single-case study design is presented with an evaluation of the clinical outcome and economic costs. METHODS: We present a description of the service context, principles of the model of care, implementation process, and an evaluation of service utilization data from health and child protection services and mental health records. A single-case longitudinal design compared service utilization data obtained up to 3 years prior to treatment with data collected one and a half years since treatment commenced. RESULTS: There were significant reductions in the number of admissions to emergency departments, mental health wards and secure units, and improvements in mental health and well-being. Yearly average time in institutional settings reduced from 69% to 7%. Cost savings in health utilization were estimated at $2 326 790. CONCLUSIONS: The Youth Wraparound model has the potential to offer improved clinical outcomes, significant cost savings over time, improved coordination between care providers, and an alternative to detention or incarceration.

Providing culturally informed mental health services to Aboriginal youth: The YouthLink model in Western Australia.

AIM: Aboriginal young people are more likely to experience mental health issues and to access mental health services than other young Australians, yet there are few culturally informed mental health programs and services available. This study describes and documents the effectiveness of the culturally sensitive model within YouthLink, a state-wide mental health service program in Western Australia for young people aged 13 to 24 years of age. METHODS: A mixed-method design including a descriptive approach reporting on the YouthLink framework and an empirical research design where 40 Aboriginal clients completed client feedback monitoring measures between 2014 and 2016. RESULTS: The YouthLink culturally informed conceptual framework adheres to best practice principles relevant to work with Indigenous people, family and communities. Aboriginal young people indicated improvement across the treatment period as shown by within-group differences between the first and last session scores on feedback measures. Therapeutic alliance (together with lower baseline acuity and female gender) also contributed significantly to positive treatment outcomes. CONCLUSIONS: Through a strong role of Aboriginal practitioners, relationships with Aboriginal communities, and greater service flexibility that embraces cultural meaning and knowledge, YouthLink has sought to enhance its response to the needs of Aboriginal youth.

12q14 Microdeletions: Additional Case Series with Confirmation of a Macrocephaly Region.

To date, there have been only a few reports of patients carrying a microdeletion in chromosome 12q14. These patients usually present with pre- and postnatal growth retardation, and developmental delay. Here we report on two additional patients with both genotype and phenotype differences. Similar to previously published cases, one patient has haploinsufficiency of the HMGA2 gene and shows severe short stature and developmental delay. The second patient is only one of a handful without the loss of the HMGA2 gene and shows a much better growth profile, but with absolute macrocephaly. This patient's deletion is unique and hence defines a likely macrocephaly locus that contributes to the general phenotype characterising the 12q14 syndrome.

Long-term efficacy of an imidacloprid 10 % / flumethrin 4.5 % polymer matrix collar (Seresto®, Bayer) against the Australian paralysis tick (Ixodes holocyclus) in dogs.

Two placebo-controlled pen studies were conducted to assess the efficacy of an imidacloprid 10 %/flumethrin 4.5 % polymer matrix collar (Seresto®, Bayer; Investigational Veterinary Product (IVP)) against the Australian paralysis tick (Ixodes holocyclus). Dogs assigned to the placebo (n = 8) or IVP (n ≥ 8) groups had collars (placebo or IVP) attached on Day 0 and were infested with 30 unfed, adult, female I. holocyclus at 14­28 day intervals over 227 days. Ticks were counted 24, 48 and 72 h post infestation to determine the acaricidal efficacy of the IVP. The acaricidal efficacy of the IVP 72 h post infestation exceeded 95 % on Days 17 (99.3 %), 59 (99.7 %), 73 (96.6 %), 87 (100.0 %), 101 (96.4 %), 115 (99.1 %) and 171 (95.8 %), but dropped on Days 45 (94.0 %) and 143 (77.8 %), and declined from Day 199 (79.9 %) to 227 (65.5 %). No adverse events related to treatment were observed. This study has demonstrated the excellent acaricidal efficacy (97.9 %) of the IVP collar against I. holocyclus 72 h post infestation over 16 weeks.