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Introduction: High demand for speech-language pathology means children sometimes wait over 12 months for services, missing out on timely support. Waiting can be a time of stress, concern, and powerlessness for caregivers. Provision of information via a website may support families and encourage active waiting. Objective: The aim of this study was to compare children’s speech, intelligibility, language, and literacy outcomes, and caregivers’ satisfaction and empowerment in active versus passive waiting conditions. Methods: Ninety-seven preschool-aged children referred to a community health speech-language pathology service in Australia were screened for eligibility. Eligible children (n =42) with speech/language difficulties were randomly allocated to: (a) active waiting (provision of a purpose-built website; n = 20), or (b) passive waiting (control group; n = 22). Pre- and post-assessments (after 6 months on a waiting list) were completed with children and caregivers by a speech-language pathologist blinded to group allocations. Results: Intention to treat (n =36) and per-protocol analyses (n =30) were conducted to measure group differences in child and caregiver outcomes at post-assessment using one-way ANCOVA, controlling for baseline scores. There were no statistically significant differences between groups for children’s speech, intelligibility, language, and literacy, or caregivers’ empowerment and satisfaction. Children in both groups made minimal gains over 6 months. Conclusions: Provision of an active waiting website did not lead to statistically significant change in child or caregiver outcomes, and children in both groups made little progress over a 6-month period. Early speech-language pathology intervention delivered with appropriate dosage is needed to optimise children’s outcomes. Until timely and effective speech-language pathology intervention can be provided for all who need it, provision of early assessments may be beneficial. There remains a need for effective ways to support children and families on waiting lists.

Much of our understanding of GH’s action stems from animal models and the generation and characterization of genetically altered or modified mice. Manipulation of genes in the GH/IGF1 family in animals started in 1982 when the first GH transgenic mice were produced. Since then, multiple laboratories have altered mouse DNA to globally disrupt Gh, Ghr, and other genes upstream or downstream of GH or its receptor. The ability to stay current with the various genetically manipulated mouse lines within the realm of GH/IGF1 research has been daunting. As such, this review attempts to consolidate and summarize the literature related to the initial characterization of many of the known gene-manipulated mice relating to the actions of GH, PRL and IGF1. We have organized the mouse lines by modifications made to constituents of the GH/IGF1 family either upstream or downstream of GHR or to the GHR itself. Available data on the effect of altered gene expression on growth, GH/IGF1 levels, body composition, reproduction, diabetes, metabolism, cancer, and aging are summarized. For the ease of finding this information, key words are highlighted in bold throughout the main text for each mouse line and this information is summarized in Tables 1, 2, 3 and 4. Most importantly, the collective data derived from and reported for these mice have enhanced our understanding of GH action.

Objective:Healthcare personnel (HCP) were recruited to provide serum samples, which were tested for antibodies against Ebola or Lassa virus to evaluate for asymptomatic seroconversion.Setting:From 2014 to 2016, 4 patients with Ebola virus disease (EVD) and 1 patient with Lassa fever (LF) were treated in the Serious Communicable Diseases Unit (SCDU) at Emory University Hospital. Strict infection control and clinical biosafety practices were implemented to prevent nosocomial transmission of EVD or LF to HCP.Participants:All personnel who entered the SCDU who were required to measure their temperatures and complete a symptom questionnaire twice daily were eligible.Results:No employee developed symptomatic EVD or LF. EVD and LF antibody studies were performed on sera samples from 42 HCP. The 6 participants who had received investigational vaccination with a chimpanzee adenovirus type 3 vectored Ebola glycoprotein vaccine had high antibody titers to Ebola glycoprotein, but none had a response to Ebola nucleoprotein or VP40, or a response to LF antigens.Conclusions:Patients infected with filoviruses and arenaviruses can be managed successfully without causing occupation-related symptomatic or asymptomatic infections. Meticulous attention to infection control and clinical biosafety practices by highly motivated, trained staff is critical to the safe care of patients with an infection from a special pathogen.

The output of the retina is organized into many detector grids, called 'mosaics', that signal different features of visual scenes to the brain1-4. Each mosaic comprises a single type of retinal ganglion cell (RGC), whose receptive fields tile visual space. Many mosaics arise as pairs, signalling increments (ON) and decrements (OFF), respectively, of a particular visual feature5. Here we use a model of efficient coding6 to determine how such mosaic pairs should be arranged to optimize the encoding of natural scenes. We find that information is maximized when these mosaic pairs are anti-aligned, meaning that the distances between the receptive field centres across mosaics are greater than expected by chance. We tested this prediction across multiple receptive field mosaics acquired using large-scale measurements of the light responses of rat and primate RGCs. ON and OFF RGC pairs with similar feature selectivity had anti-aligned receptive field mosaics, consistent with this prediction. ON and OFF RGC types that encode distinct features have independent mosaics. These results extend efficient coding theory beyond individual cells to predict how populations of diverse types of RGC are spatially arranged.

Nursing education is continuously evolving to meet Nursing and Midwifery Council (NMC) requirements for registered nurses. NMC standards state that all registered nurses are responsible for the student learning experience. However, newly qualified nurses can feel underprepared to support pre-registration student learning in the clinical area as the university setting does not facilitate formal peer support. This article will discuss the implementation of a peer facilitation scheme for pre-registration nursing students undertaking the BSc (Hons) and PGDip programmes in a higher education institution in London. The scheme trained second-year nursing students to be peer facilitators for first-year clinical skills sessions. This article will also consider the benefits of the scheme for both first and second-year student nurses.

Purpose: To compare children’s speech, language and early literacy outcomes, and caregivers' empowerment and satisfaction following provision of 12 sessions of direct intervention (therapy), or face-to-face advice or a purpose-built website (device) while waiting for therapy. Method: A four-stage randomised controlled trial was undertaken involving three- to six-year-old children referred to speech-language pathology waiting lists at two Australian community health centres over eight months (n = 222). Stage 1 (screening): 149 were eligible to participate. Stage 2 (pre-assessment): 117 were assessed. Stage 3 (intervention): 110 were randomised to advice (33), device (39) or therapy (38). Stage 4 (post-assessment): 101 were re-assessed by a speech-language pathologist blinded to the intervention condition. Result: After controlling for baseline levels, children’s speech (percentage of consonants correct) was significantly higher in the therapy group compared to the advice and device conditions. Caregivers' satisfaction was also significantly higher in the therapy condition compared to the device condition. There were no significant differences between the three conditions for children’s intelligibility, language and early literacy or caregivers' empowerment. Conclusion: Therapy resulted in significantly higher speech outcomes than the advice and device conditions and was associated with significantly greater caregiver satisfaction. Provision of a website containing evidence-based material or a single session of advice may be a viable alternative while children wait for therapy targeting intelligibility, language and early literacy, and to empower caregivers.

In the 11 years since the 2006 publication of the International Writing Center Association's (IWCA) Position Statements on Disability and Diversity, writing center scholars have continued to explore how disability issues intersect with writing center work including the development of accessible web content and interfaces (Hawkes, 2010). Recent studies have found that university websites were ineffectively designed, difficult to navigate, and omitting any representation or acknowledgment of students with disabilities (Gabel et al., 2016; Gabel & Miskovic, 2014; Meyer, 2008; Miskovic & Gabel, 2012). In this study, the primary author and four undergraduate student-researchers study where and how disability support is explicitly articulated on writing center websites from regional Institutions of Higher Education (IHEs) and how digital resources have been designed for students with disabilities. Results show that two out of the 35 writing center offices that exist at the 55 universities analyzed have a mission statement that explicitly articulates a support for students with disabilities. Writing center websites also ineffectively incorporate pictures, simple text, simple navigation, and other accessible features (71% of the 35 writing centers analyzed had websites where 21 – 70% of the content is inaccessible). Recommendations to address these problems are provided.

Dynamic spatial light modulators (SLMs) are capable of precisely modulating a beam of light by tuning the phase or intensity of an array of pixels in parallel. They can be utilized in applications ranging from image projection to beam front aberration and microscopic particle manipulation with optical tweezers. However, conventional dynamic SLMs are typically incompatible with high-power sources, as they contain easily damaged optically absorbing components. To address this, we present an SLM that utilizes a viscous film with a local thickness controlled via thermocapillary dewetting. The film is reflowable and can cycle through different patterns, representing, to the best of our knowledge, the first steps towards a dynamic optical device based on the thermocapillary dewetting mechanism.

Background: Immune checkpoint inhibitors (ICIs) provide benefit for immunogenic cancers that naturally attract T cell infiltration, but have limited benefit for patients with tumors that lack natural T cells in the tumor microenvironment (TME) including many breast cancers. Suboptimal and inconsistent immune responsiveness in many cancers is likely the result of a lack of tumor antigen expression and/or recognition together with multiple suppressive signals within the TME that provide a formidable barrier to T cell infiltration. Emerging data suggest that these factors can be overcome by combining epigenetic modulation that reprograms myeloid-derived suppressor cells (MDSCs) and upregulate T cell-attracting signals within the TME, with ICIs. Our paralleled preclinical and clinical trial investigates the mechanisms and efficacy of the epigenetic modulator, entinostat (ENT) to reprogram the immune suppressive cells within the TME. Methods: We conducted a multicenter phase 1 clinical trial (NCT02453620) of entinostat combined with nivolumab +/- ipilimumab in patients with advanced cancers including hormone-receptor positive or triple-negative breast cancer (TNBC). Mandatory tumor samples are being obtained pre-treatment, post-treatment with 2 weeks of entinostat, and 8 weeks post combination therapy with ICIs. We used immunohistochemical (IHC) for CD8 and FoxP3 to determine a ratio representative of immune infiltration in response to therapy. Preclinical studies utilize mouse models of breast cancer (NeuN and 4T1) and mirror the treatment scheme used in the clinical trial. We employed multiparameter flow cytometry, single cell RNA sequencing, bulk RNA sequencing of tumor specimens and patient samples to specifically interrogate the role of ENT in modulating STAT3 as a master regulator of downstream inflammatory pathways. Results: With regard to the clinical trial, out of 35 patients enrolled, 11 were diagnosed with breast cancer. We observed 4 partial responses, 2 responses in patients with breast cancer, with an ORR of 12%. We have almost completed accrual of our expansion cohort of 15 patients with advanced HER2 negative breast cancer. The primary outcomes of the clinical trial will be reported elsewhere, here we are focusing on important correlative findings which suggest a combination of ENT with ICIs alters CD8/FoxP3 ratios in certain patients. Bulk-RNA sequencing or patient samples is underway. Preliminary data from animal models obtained using scRNA-seq has begun to elucidate altered MDSC signaling pathways, and to identify gene expression changes in immune, stromal, and tumor cells following treatment with ENT. These data are also expected to identify new targets for ICI sensitization. Conclusions: Preliminary results with IHC staining suggests increased immune infiltration with combination therapy. Sequencing analysis will likely provide deeper insight into mechanisms driving response. The mechanisms of response to ICIs in patients with breast cancer have yet to be elucidated. These studies will provide the necessary scientific evidence to uncover mechanisms behind the transformation of the immunosuppressive TME and provide new targets that could improve clinical response to ICIs to maximize patient survival. The core biological themes explored will likely have a broad impact in the field of breast cancer and affect the paradigm of therapies available to patients in the clinic. These findings will help determine how treatment with ICIs will be successful to obtain durable responses for breast cancer patients. Citation Format: Evanthia T Roussos Torres, Luciane Tsukamoto Kagohara, Emily Davis, Christine Rafie, Brian Christmas, Qingfeng Zhu, Chenguang Wang, David Lim, Robert Anders, Elana Fertig, Vincent Chung, Patricia Lorusso, Adam Brufsky, Elizabeth M Jaffee, Vered Stearns, Roisin Connolly. Reprogramming the suppressive tumor microenvironment of breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-06.

Background Community health workers play an important role in health service delivery and are increasingly involved in behaviour change interventions, including for hygiene-related behaviour change. However, their role and capacity to deliver behaviour change interventions, particularly in high-density urban settlements, remain under-researched. This study examines the behaviour change-related activities of community health volunteers (CHVs)—community health workers affiliated with the Kenyan Ministry of Health—in a peri-urban settlement in Kenya, in order to assess their capabilities, opportunities to work effectively, and sources of motivation. Methods This mixed-methods study included a census of 16 CHVs who work in the study area. All CHVs participated in structured observations of their daily duties, structured questionnaires, in-depth interviews, and two focus group discussions. Structured data were analysed descriptively. Thematic content analysis was followed for qualitative data. Results were synthesized and interpreted using the capability, opportunity, motivation for behaviour change framework, COM-B. Results In addition to their responsibilities with the Ministry of Health, CHVs partnered with a range of non-governmental organizations engaged in health and development programming, often receiving small stipends from these organizations. CHVs reported employing a limited number of behaviour change techniques when interacting with community members at the household level. Capability: While supervision and support from the MOH was robust, CHV training was inconsistent and inadequate with regard to behaviour change and CHVs often lacked material resources necessary for their work. Opportunity: CHVs spent very little time with the households in their allocated catchment area. The number of households contacted per day was insufficient to reach all assigned households within a given month as required and the brief time spent with households limited the quality of engagement. Motivation: Lack of compensation was noted as a demotivating factor for CHVs. This was compounded by the challenging social environment and CHVs’ low motivation to encourage behaviour change in local communities. Conclusions In a complex urban environment, CHVs faced challenges that limited their capacity to be involved in behaviour change interventions. More resources, better coordination, and additional training in modern behaviour change approaches are needed to ensure their optimal performance in implementing health programmes.

The Santa Cruz/Silicon Valley New Teacher Project -- under the aegis of the New Teacher Center -- devised a program to train teacher mentors to help new teachers incorporate the Common Core standards into their teaching. The three-year program yielded five critical lessons: Mentors need ongoing support to develop their readiness and willingness to guide new teachers in implementing the Common Core; mentors need to be grand generalists of the Common Core so they can work with teachers in many contexts; rolling out the Common Core requires leveraging resources and relationships in new ways; working with new teachers is a balancing act; and mentors and new teachers can quickly become Common Core leaders.

Childhood diarrhea is one of the leading causes of morbidity and mortality in children under five in low and middle-income countries, second only to respiratory illness. The mouthing behavior that is common in children exposes them to fecal-orally transmitted pathogens that can result in diarrhea; however, there is a need for further evidence on specific exposure routes. This study describes the frequency and diversity of two important routes of enteric pathogen exposure among infants 3-9 months of age: infant oral contact behavior and caregiver handwashing behavior. Data were collected through structured observations of 25 index infants for the oral contact data and 25 households for the caregiver handwashing data in a peri-urban setting in Kisumu (Obunga), Kenya. Breast was the most common type of oral contact event with an average of 3.00 per observation period and 0.5 events per hour. This was followed by a range of physical objects with an average of 2.49 per observation and 0.4 events per hour. The "infant's own hands" was the third most common oral contact, with an average of 2.16 events per hour, and 0.4 oral contact events per hour. Food and liquids were the 4th and 5th most common oral contact events with an average of 1.64 food contacts and 0.52 liquid oral contact events per observation period. Feeding events, including breastfeeding, were the most commonly observed key juncture-71% of total junctures observed were caregivers feeding children. This was followed by child cleaning (23%), caregiver toilet uses at (4%), and lastly food preparation at 2%. HWWS was observed only once before a feeding event (1%), twice after cleaning a child (9%), and twice after caregiver toilet use (40%). The combined implication of data from observing oral contact behavior in children and hand hygiene of caregivers suggests that caregiver hand hygiene prior to feeding events and after cleaning a child are priority interventions.

The purpose of this study is to identify how the epigenetic modulator entinostat reprograms myeloid derived suppressor cells (MDSCs) to prime the tumor microenvironment (TME) and modulate immunotherapy response. Early trials investigating single agent ICIs, anti-CTLA-4 and anti-PD-1/PD-L1, resulted in overall response rates of 5-20% in patients with metastatic HER2 positive breast cancer but little is understood about use of these therapies in patients with early stage/ primary disease. Suboptimal and inconsistent immune responsiveness is likely the result of multiple suppressive signals within the TME that provide a formidable barrier to T cell infiltration leading to an opportunity for TME modulation to potentially improve response. We and others have shown that immunosuppressive factors can be overcome by adding the class 1 histone deacetylase inhibitor, entinostat, to ICIs to reprogram MDSCs and upregulate T cell attracting signals within the TME. We hypothesize that gene expression signatures of reprogrammed MDSCs are predictive of response with subsequent immunotherapy treatment. To test this hypothesis, we used the neu-N syngeneic mouse model of HER2 positive breast cancer. We investigated differences in survival and tumor burden in response to combinations of entinostat with anti-PD-1 and anti-CTLA-4. Having previously identified MDSCs as important targets of entinostat that modulate response to ICIs, we used methods we developed to study MDSC function. Given the broad effects of entinostat on global gene expression including that of MDSCs, we used single cell RNA-seq (scRNA-seq) on primary tumors and isolated intratumoral MDSCs to determine what is driving changes in MDSC function in primary tumors. We plan to use data obtained from scRNA-seq to develop signatures of response and identify changes in responders vs. non-responders to help develop biomarkers of response in primary disease. Our results thus far show that treatment with entinostat + ICIs improves survival, and decreases tumor burden in primary tumors. Ex-vivo studies of MDSCs demonstrate changes in immunosuppressive capabilities of MDSCs and show differences in infiltration and function of granulocytic vs. monocytic MDSCs. We expect that evaluation of the ongoing sequencing data will identify more specific immune targets within primary TME and help us understand the importance of targeting MDSCs in early disease. We predict this work will identify additional candidate targets for therapeutic testing to convert breast cancers into immune responsive tumors, and that this will facilitate improved response to ICIs that will ultimately translate into improved survival of patients with breast cancer. Citation Format: Evanthia T. Roussos Torres, Christine Rafie, Emily Davis, Luciane T. Kagohara, Elana J. Fertig, Elizabeth M. Jaffee. Sequencing the tumor microenvironment and myeloid derived suppressor cells to understand response to immunotherapy in primary HER2 positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5027.

The purpose of this study was to assess the effectiveness of non contact low‐frequency ultrasound on the healing of suspected deep tissue injury (SDTI). Participants were adults ranging in age from 28 to 93 years old, with multiple diagnoses including anaemia, diabetes mellitus and hypertension. Data were examined retrospectively on 85 patients (intervention group = 43 and non intervention group = 42) with 127 SDTI (intervention group = 64 and non intervention group = 63). Participants in both groups received standard of care for treating pressure ulcers. A severity score was used to assess SDTI severity before treatment and healing/progression after treatment. This scale measures surface area, wound colour/tissue assessment, and skin integrity with potential scores of 3 to 18 (higher scores indicate greater severity). A significant difference in changes in wound severity was found (t = 5·67, P < 0.000). Difference in mean change scores was 2·52 on the 3–18 severity scale. The decrease in wound severity for the intervention group was 1·45. Severity in the non intervention group increased by 1·06. This exploratory study of the effect of the non contact low‐frequency ultrasound provides initial findings that support its use with SDTI.

We present a scheme for locking optical cavities with arbitrary detuning by many linewidths from resonance using an electro-optic modulator that can provide arbitrary ratios of amplitude-to-phase modulation. We demonstrate our scheme on a Fabry–Perot cavity, and show that a well-behaved linear error signal can be obtained by demodulating the reflected light from a cavity that is detuned by several linewidths., National Science Foundation (U.S.) (PHY-0757058)

Introduction Ventolin Nebules® (reference product; GlaxoSmithKline) was the first licensed nebulizer solution containing the rapid-onset, short-acting β2-agonist salbutamol. Salbutamol Steri-Neb™ (comparator; Teva Pharmaceuticals, Inc.) has the same chemical composition as the reference product. This study evaluated whether the effectiveness of the comparator is non-inferior to the reference product alongside concomitant medications during real-life clinical management of COPD exacerbations. Safety in terms of adverse events (AEs) was also examined. Methods This matched (1:1) historical cohort study evaluated data from 2 UK primary care databases on patients prescribed the salbutamol comparator or reference. The study included a 1-year baseline period, starting 1 year before the index prescription date, and 1-year outcome period. Cohorts were matched for baseline COPD respiratory medications. The primary outcome was analysis of non-inferiority for the comparator versus reference product for the rate of moderate and severe COPD exacerbations. Non-inferiority was satisfied if the 95% confidence interval (CI) upper limit for mean differences in proportions between treatments was

BACKGROUND AND OBJECTIVES: Although intrauterine devices (IUDs) and subdermal implants (SDI) are recommended as first-line contraception for the majority of women by the American College of Obstetrics and Gynecology these methods of long-acting reversible contraception (LARC) are underutilized. Some concerns regarding their use include cost of placement side effects and perception of frequent early removal. This study evaluated satisfaction with LARC frequency and reasons behind early removal in a family medicine setting. METHODS: Women > 18 years seen for placement of removal of an IUD or SDI were identified from billing data and surveyed via telephone to determine satisfaction and side effects with LARC. Additional demographic information was extracted from the electronic health record. RESULTS: Of the 132 respondents (response rate 61.4%) 58.3% had IUDs and 41.7% had SDIs placed. Early removal occurred in 24.2% of women and 72.7% were satisfied with their contraceptive choice. Younger and nulliparous women were more likely to have an SDI placed whereas older and multiparous women chose the IUD. Younger nulliparous women were less likely to have LARC removed early. Pain (more commonly reported with the IUD) and increased frequency in bleeding (more commonly reported with the SDI) were associated with early removal rates. CONCLUSIONS: Most women who received LARC were satisfied with their contraceptive choice and only one in four had the LARC removed early. This is significantly better than continuation rates with other contraceptive methods. Younger nulliparous women were good candidates for LARC continuing their use more than older multiparous women. Improved counseling regarding pain and changes in menstrual bleeding patterns may impact early removal of IUDs and SDIs respectively.

Prescribing patterns in chronic obstructive pulmonary disease (COPD) are often inconsistent with published guidelines. This retrospective, observational study utilised data from the Optimum Patient Care Research Database to examine the changes in COPD prescribing patterns over time and to identify predictors of physician treatment choice for patients newly diagnosed with COPD. Initial therapy was defined as the treatment(s) prescribed at or within 1 year before COPD diagnosis. Changes over time were assessed in three cohorts based on the date of diagnosis: (1) 1997–2001; (2) 2002–2006; and (3) 2007–2010. Factors affecting the odds of being prescribed any initial therapy or any initial maintenance therapy were identified by univariable and multivariable logistic regression. The analysis included 20,154 patients, 45% of whom were prescribed an initial regimen containing an inhaled corticosteroid (ICS), whereas 28% received no initial pharmacological treatment. Prescribing of ICS monotherapy decreased over time, as did the proportion of patients receiving no therapy at or within 1 year before diagnosis. Comorbid asthma, a high exacerbation rate, increased symptoms and poor lung function each increased the likelihood of being prescribed any initial therapy or initial maintenance therapy; comorbid asthma and an annual rate of ⩾3 exacerbations were the strongest predictors. In conclusion, our analyses revealed major differences between actual prescribing behaviour and guideline recommendations for patients with newly diagnosed COPD, with many patients receiving no treatment and large numbers of patients receiving ICS-containing regimens. Predictors of initial therapy were identified.

We introduce NetKet, a comprehensive open source framework for the study of many-body quantum systems using machine learning techniques. The framework is built around a general and flexible implementation of neural-network quantum states, which are used as a variational ansatz for quantum wavefunctions. NetKet provides algorithms for several key tasks in quantum many-body physics and quantum technology, namely quantum state tomography, supervised learning from wavefunction data, and ground state searches for a wide range of customizable lattice models. Our aim is to provide a common platform for open research and to stimulate the collaborative development of computational methods at the interface of machine learning and many-body physics., SoftwareX, 10, ISSN:2352-7110