An exploration of the psychosocial effects that school-age children with Child Absence Epilepsy (CAE) experience when their condition is misdiagnosed as Attention-Deficit/Hyperactivity Disorder (ADHD)

In today's society, the misdiagnosis of school-age children with the neurological condition Child Absence Epilepsy (CAE) as having Attention-Deficit/Hyperactivity Disorder (ADHD) has a low profile. This may be because of the lack of popular awareness of CAE. The increasing social salience towards the neuropsychological condition of ADHD places these children at risk of experiencing high psychosocial effects. Many symptoms of CAE are also associated with ADHD. However if the condition is misdiagnosed as ADHD, the child with CAE is often mistreated, both medically and socially until the correct diagnosis is made. There is little research available on the psychosocial effects of the misdiagnosis of epilepsy as ADHD, and none available relating to CAE. This research study uses case study methodology to focus on how children with CAE are psychosocially affected at the time of the misdiagnosis of ADHD and subsequently. It also explores the experiences of their parents. An in-depth interview method was adopted to gather the personal recollections of these effects directly from the ten participants in this study. The participants were found with the assistance of Epilepsy Australia and constituted one adolescent from five different families who had experienced the sequence of events and effects under investigation, and a parent (guardian) who cared for these children during this period. The findings of this research indicate that as a result of labelling, these children were misjudged in their communities, leaving strong psychosocial effects on each of the child participants who had previously been misdiagnosed with ADHD. These effects include low self-esteem, insecurity and fear experienced most often in the company of peers. As a result, when reaching adulthood, most of these participants chose to isolate themselves from social contact whenever possible. The findings offer a basis for further research in the area

Long survival of primary diffuse leptomeningeal gliomatosis following radiotherapy and temozolomide: case report and literature review

<p>Abstract</p> <p>Objective</p> <p>Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare neoplasm with a short survival time of a few months. there is currently no standardized therapeutic approach for PDLG.</p> <p>Materials and methods</p> <p>We report on a 53-year-old male patient who presented with epileptic seizures, gait disturbance, paraparesis and sensory deficits in the dermatomes T8-10.</p> <p>Results</p> <p>Magnetic resonance imaging (MRI) revealing numerous spinal and cranial gadolinium-enhancing nodules in the meninges and histopathology led us to diagnose primary diffuse leptomeningeal gliomatosis with WHO grade III astrocytic cells. Consecutively, the patient underwent craniospinal radiotherapy (30 Gy) and 11 sequential cycles of temozolomide. This regimen led to partial tumor regression. Thirteen months later, spinal MRI revealed tumor progression. Second-line chemotherapy with 5 cycles of irinotecan and bevacizumab did not prevent further clinical deterioration. The patient died twenty-two months after diagnosis, being the longest survival time described thus far with respect to PDLG consisting of astrocytic tumor cells.</p> <p>Conclusions</p> <p>Radiochemotherapy including temozolomide, as established standard therapy for brain malignant astrocytomas, might be valid as a basic therapeutic strategy for this PDLG subtype.</p

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up.

PurposeIn the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P &lt; 0.001]. Herein, we report results overall and by subgroups with extended follow-up.MethodsIn this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).ResultsAfter a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P &lt; 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained.ConclusionsWith approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427

The Future of Parenting Programs: II Implementation

This article examines the role that implementation science can play in evidence-based parenting programs. Although parenting programs can support parents in their caregiving roles, adapting and taking an evidence-based approach from one place to another without attending to implementation factors may contribute to poor impact in a new setting. Implementation science enables researchers to move beyond monitoring and evaluation of outcomes of a parenting program to understanding the process of putting the program into practice. Factors such as whether the program meets the needs of families and communities, how to secure buy-in from key stakeholders, what training and supervision are needed for the workforce, and ways that parenting programs can be integrated in existing infrastructure are all critical to successful implementation. Quality improvement can be built into the implementation process through feedback loops that inform rapid changes and testing cycles over time as a program is implemented. If researchers lead initial implementation of parenting programs, they must determine how the program can continue to work when using community workers and local systems rather than researchers. Open access components are especially important for the implementation of parenting programs in low- and middle-income countries to avoid prohibitive costs of proprietary programs and to benefit from flexibility in adapting components to meet the needs of particular local populations. Parenting programs benefit when policy makers, program leaders, and researchers attend not only to the what but also to the how of implementation.Objective.Design.Results.Conclusions

Aspects of ABJM orbifolds with discrete torsion

We analyze orbifolds with discrete torsion of the ABJM theory by a finite subgroup $\Gamma$ of $SU(2)\times SU(2)$ . Discrete torsion is implemented by twisting the crossed product algebra resulting after orbifolding. It is shown that, in general, the order $m$ of the cocycle we chose to twist the algebra by enters in a non trivial way in the moduli space. To be precise, the M-theory fiber is multiplied by a factor of $m$ in addition to the other effects that were found before in the literature. Therefore we got a $\mathbb{Z}_{\frac{k|\Gamma|}{m}}$ action on the fiber. We present a general analysis on how this quotient arises along with a detailed analysis of the cases where $\Gamma$ is abelian

Pathogen quantitation in complex matrices: a multi-operator comparison of DNA extraction methods with a novel assessment of PCR inhibition

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Mycobacterium bovis is the aetiological agent of bovine tuberculosis (bTB), an important recrudescent zoonosis, significantly increasing in British herds in recent years. Wildlife reservoirs have been identified for this disease but the mode of transmission to cattle remains unclear. There is evidence that viable M. bovis cells can survive in soil and faeces for over a year. METHODOLOGY/PRINCIPAL FINDINGS: We report a multi-operator blinded trial for a rigorous comparison of five DNA extraction methods from a variety of soil and faecal samples to assess recovery of M. bovis via real-time PCR detection. The methods included four commercial kits: the QIAamp Stool Mini kit with a pre-treatment step, the FastDNA® Spin kit, the UltraClean™ and PowerSoil™ soil kits and a published manual method based on phenol:chloroform purification, termed Griffiths. M. bovis BCG Pasteur spiked samples were extracted by four operators and evaluated using a specific real-time PCR assay. A novel inhibition control assay was used alongside spectrophotometric ratios to monitor the level of inhibitory compounds affecting PCR, DNA yield, and purity. There were statistically significant differences in M. bovis detection between methods of extraction and types of environmental samples; no significant differences were observed between operators. Processing times and costs were also evaluated. To improve M. bovis detection further, the two best performing methods, FastDNA® Spin kit and Griffiths, were optimised and the ABI TaqMan environmental PCR Master mix was adopted, leading to improved sensitivities. CONCLUSIONS: M. bovis was successfully detected in all environmental samples; DNA extraction using FastDNA® Spin kit was the most sensitive method with highest recoveries from all soil types tested. For troublesome faecal samples, we have used and recommend an improved assay based on a reduced volume, resulting in detection limits of 4.25×10(5) cells g(-1) using Griffiths and 4.25×10(6) cells g(-1) using FastDNA® Spin kit.This work was supported by Biotechnology and Biological Sciences Research Council BBSRCBB/E020925/1 grant to OC and EMHW, and Department for Environment, Food and Rural Affairs, DEFRA SE3231 grant to EMHW and OC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Measurement of migration of a humeral head resurfacing prosthesis using radiostereometry without implant marking: An experimental study

Today, the shoulder joint is the third most commonly replaced joint after the hip and knee joints and the incidence is increasing. In Sweden, 1863 primary Shoulder Arthroplasties and 195 revisions were performed in 2017. The most common diagnoses are Osteoarthritis and irreparable tears of the rotator cuff, with or without arthropathy, often referred to as cuff tear arthropathy. Different Shoulder Arthroplasty (SA) concepts include anatomical total shoulder arthroplasty (TSA), hemiarthroplasty (HSA) and reversed shoulder arthroplasty, but also humeral head resurfacing (HHR) and stemless arthroplasties. All concepts offer pain relief, improvement of function and in quality of life for the different diagnoses. Unfortunately, there are sometimes complications after SA. They involve periprosthetic joint infection, humeral and glenoid fractures, stress shielding, loosening of the glenoid and humeral component but also glenoid erosion and cuff rupture. Some of these complications are most common within 1 year after operation, some after several years, both may lead to a revision. This, together with the fact that new designs of implants and methods of fixation of SA continues to develop, stresses the importance of continuous monitoring of implant survival and follow-up. The overall aim of this thesis was to describe clinical examples of different methods to assess the outcome after Shoulder Arthroplasty. The most common methods are clinical examination, radiographic assessment, Patient Reported Outcome Measure (PROM), National Joint registries, where revisions are an important outcome, but also Clinical Trials. All of these methods are used in one or more of the 4 papers in this thesis and shows the complexity of the topic and the practical work. In paper I we used Radio Stereometric Analysis (RSA) in an experimental set-up and concluded that marker-free RSA can be used for a humeral head resurfacing arthroplasty. In paper II we used data from the Swedish Shoulder Arthroplasty Registry (SSAR) with PROM and revisions to conclude that age is the only factor that affects revision when comparing HSA and HHR. Paper III is a long-time follow-up of a Randomized controlled study where we used radiological assessment, PROM and revisions. The conclusion was that both TSA and HSA develop severe radiological changes 10 year after primary operation. Paper IV is a prospective RSA cohort study where we also evaluated PROM and revisions. The conclusion is that HHR seems to obtain a secure fixation in the humerus, after an initial migration. But also that the prostheses shows continuous glenoid wear. The main conclusion of this thesis is that patient’s operated with SA needs continuous monitoring and several methods may be used to evaluate the outcome

Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study

Purpose: Although chemotherapy is standard of care for met- astatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a “cold” tumor. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine derived from 7 tumor- associated antigens (TAA) frequently expressed in mCRC. This study assessed PolyPEPI1018 combined with first-line maintenance therapy in patients with MSS mCRC. Patients and Methods: Eleven patients with MSS mCRC received PolyPEPI1018 and Montanide ISA51VG adjuvant subcutaneously, combined with fluoropyrimidine/biologic follow- ing first-line induction with chemotherapy and a biologic (NCT03391232). In Part A of the study, 5 patients received a single dose; in Part B, 6 patients received up to three doses of Poly- PEPI1018 every 12 weeks. The primary objective was safety; sec- ondary objectives were preliminary efficacy, immunogenicity at peripheral and tumor level, and immune correlates. Results: PolyPEPI1018 vaccination was safe and well tolerated. No vaccine-related serious adverse event occurred. Eighty percent of patients had CD8þ T-cell responses against ≥3 TAAs. Increased density of tumor-infiltrating lymphocytes were detected post- treatment for 3 of 4 patients’ liver biopsies, combined with increased expression of immune-related gene signatures. Three patients had objective response according to RECISTv1.1, and 2 patients qual- ified for curative surgery. Longer median progression-free survival for patients receiving multiple doses compared with a single dose (12.5 vs. 4.6 months; P 1⁄4 0.017) suggested a dose–efficacy correlation. The host HLA genotype predicted multi-antigen– specific T-cell responses (P 1⁄4 0.01) indicative of clinical outcome. Conclusions: PolyPEPI1018 added to maintenance chemother- apy for patients with unresectable, MSS mCRC was safe and associated with specific immune responses and antitumor activity warranting further confirmation in a randomized, controlled setting

BPS Spectrum, Indices and Wall Crossing in N=4 Supersymmetric Yang-Mills Theories

BPS states in N=4 supersymmetric SU(N) gauge theories in four dimensions can be represented as planar string networks with ends lying on D3-branes. We introduce several protected indices which capture information on the spectrum and various quantum numbers of these states, give their wall crossing formula and describe how using the wall crossing formula we can compute all the indices at all points in the moduli space.Comment: LaTeX file, 33 pages, 15 figure

Results from Beam Commissioning of an SRF Plug Gun Cavity Photoinjector

Superconducting rf photo electron injectors SRF photoinjectors hold the promise to deliver high brightness, high average current electron beams for future light sources or other applications demanding continuous wave operation of an electron injector. This paper discusses results from beam commissioning of a hybrid SRF photoinjector based on a Pb coated plug and a Nb rf gun cavity for beam energies up to 2.5MeV at Helmholtz Zentrum Berlin HZB . Emittance measurements and transverse phase space characterization with solenoid scan and slitmask methods will be presente