Global services and support for children with developmental delays and disabilities: Bridging research and policy gaps

Summary: 1. The United Nations Sustainable Development Goals and the UN Convention on the Rights of the Child (CRC) envision an inclusive society in which health and education contribute to the well-being of all. To achieve this vision, children with developmental delays and behavioral, cognitive, mental, and neurological disabilities need greater access to health care, early childhood care and development services, and education. 2. Improved population-level detection, alongside screening, assessment, and linkage to evidence-based, intersectoral services in the first years of life, can help maximize capabilities and increase the chances of social inclusion for children with developmental delays and disabilities. 3. Educational programs for children with delays and disabilities whose service delivery structure supports the ability of parents to work should be encouraged so that parents can participate in achieving children’s educational goals while also meeting their financial needs. 4. Parents and caregivers who receive training in psychosocial interventions and ongoing support can help children with delays and disabilities thrive in family contexts. 5. Family mental health influences the developmental trajectory of children. Ensuring that parents and caregivers have access to affordable, quality mental health services helps to prevent poor outcomes for children. 6. Rigorous evaluation, continuous quality improvement, and regular monitoring of the programmatic outcomes of services and policy approaches targeting children and caregivers would inform their implementation and serve to disseminate lessons learned from successful policy and program implementation

Femtosecond photoelectron circular dichroism of chemical reactions

Understanding the chirality of molecular reaction pathways is essential for a broad range of fundamental and applied sciences. However, the current ability to probe chirality on the time scale of chemical reactions remains very limited. Here, we demonstrate time-resolved photoelectron circular dichroism (TRPECD) with ultrashort circularly polarized vacuum-ultraviolet (VUV) pulses from a table-top source. We demonstrate the capabilities of VUV-TRPECD by resolving the chirality changes in time during the photodissociation of atomic iodine from two chiral molecules. We identify several general key features of TRPECD, which include the ability to probe dynamical chirality along the complete photochemical reaction path, the sensitivity to the local chirality of the evolving scattering potential, and the influence of electron scattering off dissociating photofragments. Our results are interpreted by comparison with novel high-level ab-initio calculations of transient PECDs from molecular photoionization calculations. Our experimental and theoretical techniques define a general approach to femtochirality.Comment: 17 pages, 6 figures, 57 references, Accepted in Science Advance

Characterising precipitate evolution in multi-component cast aluminium alloys using small-angle X-ray scattering

Aluminium alloys can be strengthened significantly by nano-scale precipitates that restrict dislocation movement. In this study, the evolution of inhomogenously distributed trialuminide precipitates in two multi component alloys was characterised by synchrotron small angle Xray scattering (SAXS). The appropriate selection of reference sample and data treatment required to successfully characterise a low volume fraction of precipitates in multi-component alloys via SAXS was investigated. The resulting SAXS study allowed the analysis of statistically significant numbers of precipitates (billions) as compared to electron microscopy (hundreds). Two cast aluminium alloys with different volume fractions of Al3ZrxV1-x precipitates were studied. Data analysis was conducted using direct evaluation methods on SAXS spectra and the results compared with those from transmission electron microscopy (TEM). Precipitates were found to attain a spherical structure with homogeneous chemical composition. Precipitate evolution was quantified, including size, size distribution, volume fraction and number density. The results provide evidence that these multi-component alloys have a short nucleation stage, with coarsening dominating precipitate size. The coarsening rate constant was calculated and compared to similar precipitate behaviour

Formyltetrahydrofolate Synthetase Gene Diversity in the Guts of Higher Termites with Different Diets and Lifestyles

In this study, we examine gene diversity for formyl-tetrahydrofolate synthetase (FTHFS), a key enzyme in homoacetogenesis, recovered from the gut microbiota of six species of higher termites. The "higher" termites (family Termitidae), which represent the majority of extant termite species and genera, engage in a broader diversity of feeding and nesting styles than the "lower" termites. Previous studies of termite gut homoacetogenesis have focused on wood-feeding lower termites, from which the preponderance of FTHFS sequences recovered were related to those from acetogenic treponemes. While sequences belonging to this group were present in the guts of all six higher termites examined, treponeme-like FTHFS sequences represented the majority of recovered sequences in only two species (a wood-feeding Nasutitermes sp. and a palm-feeding Microcerotermes sp.). The remaining four termite species analyzed (a Gnathamitermes sp. and two Amitermes spp. that were recovered from subterranean nests with indeterminate feeding strategies and a litter-feeding Rhynchotermes sp.) yielded novel FTHFS clades not observed in lower termites. These termites yielded two distinct clusters of probable purinolytic Firmicutes and a large group of potential homoacetogens related to sequences previously recovered from the guts of omnivorous cockroaches. These findings suggest that the gut environments of different higher termite species may select for different groups of homoacetogens, with some species hosting treponeme-dominated homoacetogen populations similar to those of wood-feeding, lower termites while others host Firmicutes-dominated communities more similar to those of omnivorous cockroaches

Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance.

Disease progression and relapse of chronic myeloid leukemia (CML) are caused by therapy resistant leukemia stem cells (LSCs), and cure relies on their eradication. The microenvironment in the bone marrow (BM) is known to contribute to LSC maintenance and resistance. Although leukemic infiltration of the spleen is a hallmark of CML, it is unknown whether spleen cells form a niche that maintains LSCs. Here, we demonstrate that LSCs preferentially accumulate in the spleen and contribute to disease progression. Spleen LSCs were located in the red pulp close to red pulp macrophages (RPM) in CML patients and in a murine CML model. Pharmacologic and genetic depletion of RPM reduced LSCs and decreased their cell cycling activity in the spleen. Gene expression analysis revealed enriched stemness and decreased myeloid lineage differentiation in spleen leukemic stem and progenitor cells (LSPCs). These results demonstrate that splenic RPM form a niche that maintains CML LSCs in a quiescent state, resulting in disease progression and resistance to therapy

Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance

Disease progression and relapse of chronic myeloid leukemia (CML) are caused by therapy resistant leukemia stem cells (LSCs), and cure relies on their eradication. The microenvironment in the bone marrow (BM) is known to contribute to LSC maintenance and resistance. Although leukemic infiltration of the spleen is a hallmark of CML, it is unknown whether spleen cells form a niche that maintains LSCs. Here, we demonstrate that LSCs preferentially accumulate in the spleen and contribute to disease progression. Spleen LSCs were located in the red pulp close to red pulp macrophages (RPM) in CML patients and in a murine CML model. Pharmacologic and genetic depletion of RPM reduced LSCs and decreased their cell cycling activity in the spleen. Gene expression analysis revealed enriched stemness and decreased myeloid lineage differentiation in spleen leukemic stem and progenitor cells (LSPCs). These results demonstrate that splenic RPM form a niche that maintains CML LSCs in a quiescent state, resulting in disease progression and resistance to therapy

Translating the BDI and BDI-II into the HAMD and vice versa with equipercentile linking

Abstract Aims The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale. Methods We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method. Results The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16. Conclusions The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research

Comparison of bacterial microbiota of the predatory mite Neoseiulus cucumeris (Acari: Phytoseiidae) and its factitious prey Tyrophagus putrescentiae (Acari: Acaridae)

Neoseiulus cucumeris is a predatory mite used for biological control of arthropod pests. Mass-reared predators are fed with factitious prey mites such as Tyrophagus putrescentiae. Although some information on certain endosymbionts of N. cucumeris and T. putrescentiae exists, it is unclear whether both species share bacterial communities. The bacterial communities in populations of predator and prey mites, as well as the occurence of potential acaropathogenic bacteria were analyzed. The comparisons were based on the following groups: (i) N. cucumeris mass-production; (ii) N. cucumeris laboratory population with disease symptoms; (iii) T. putrescentiae pure populations and; (iv) T. putrescentiae from rearing units of N. cucumeris. Only 15% of OTUs were present in all samples from predatory and prey mite populations (core OTUs): the intracellular symbionts Wolbachia, Cardinium, plus other Blattabacterium-like, Solitalea-like, and Bartonella-like symbionts. Environmental bacteria were more abundant in predatory mites, while symbiotic bacteria prevailed in prey mites. Relative numbers of certain bacterial taxa were significantly different between the microbiota of prey mites reared with and without N. cucumeris. No significant differences were found in the bacterial communities of healthy N. cucumeris compared to N. cucumeris showing disease symptoms. We did not identify any confirmed acaropathogenic bacteria among microbiota

The DARE study of relapse prevention in depression: design for a phase 1/2 translational randomised controlled trial involving mindfulness-based cognitive therapy and supported self monitoring

<p>Abstract</p> <p>Background</p> <p>Depression is a common condition that typically has a relapsing course. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of the condition. Mindfulness-based cognitive therapy (MBCT) is a group-based intervention that has shown efficacy in reducing depressive relapse. While trials of MBCT to date have met the core requirements of phase 1 translational research, there is a need now to move to phase 2 translational research - the application of MBCT within real-world settings with a view to informing policy and clinical practice. The aim of this trial is to examine the clinical impact and health economics of MBCT under real-world conditions and where efforts have been made to assess for and prevent resentful demoralization among the control group. Secondary aims of the project involve extending the phase 1 agenda to an examination of the effects of co-morbidity and mechanisms of action.</p> <p>Methods/Design</p> <p>This study is designed as a prospective, multi-site, single-blind, randomised controlled trial using a group comparison design between involving the intervention, MBCT, and a self-monitoring comparison condition, Depression Relapse Active Monitoring (DRAM). Follow-up is over 2 years. The design of the study indicates recruitment from primary and secondary care of 204 participants who have a history of 3 or more episodes of Major Depression but who are currently well. Measures assessing depressive relapse/recurrence, time to first clinical intervention, treatment expectancy and a range of secondary outcomes and process variables are included. A health economics evaluation will be undertaken to assess the incremental cost of MBCT.</p> <p>Discussion</p> <p>The results of this trial, including an examination of clinical, functional and health economic outcomes, will be used to assess the role that this treatment approach may have in recommendations for treatment of depression in Australia and elsewhere. If the findings are positive, we expect that this research will consolidate the evidence base to guide the decision to fund MBCT and to seek to promote its availability to those who have experienced at least 3 episodes of depression.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry: <a href="http://www.anzctr.org.au/ACTRN12607000166471.aspx">ACTRN12607000166471</a></p