•Development is shaped by social touch, as shown by animal models and human studies.•We predict different long-term effects depending on valence, intensity, and timing.•We review the literature on ...social touch in light of these variables.•We identify gaps in the literature needed to design second-generation models.
In this paper, our goal is to explore what is known about the role of social touch during development. We first address the neural substrates of social touch and the role of tactile experience in neural development. We discuss natural variation in early exposure to social touch, followed by a discussion on experimental manipulations of social touch during development and “natural experiments”, such as early institutionalization. We then consider the role of other developmental and experiential variables that predict social touch in adults. Throughout, we propose and consider new theoretical models of the role of social touch during development on later behavior and neurobiology.
ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).
Patients with UC ...were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks.
Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration.
Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.
This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017-004166-10).
Background. In June 2000, the hospital-acquired Clostridium difficile (CD) infection rate in our hospital (University of Pittsburgh Medical Center–Presbyterian, Pittsburgh, PA) increased to 10.4 ...infections per 1000 hospital discharges (HDs); the annual rate increased from 2.7 infections per 1000 HDs to 7.2 infections per 1000 HDs and was accompanied by an increase in the frequency of severe outcomes. Forty-seven (51%) of 92 HA CD isolates in 2001 were identified as the “epidemic BI strain.” A comprehensive CD infection control “bundle” was implemented to control the outbreak of CD infection. Methods. The CD infection control bundle consisted of education, increased and early case finding, expanded infection-control measures, development of a CD infection management team, and antimicrobial management. Process measures, antimicrobial usage, and hospital-acquired CD infection rates were analyzed, and CD isolates were typed. Results. The rates of compliance with hand hygiene and isolation were 75% and 68%, respectively. The CD management team evaluated a mean of 31 patients per month (11% were evaluated for moderate or severe disease). Use of antimicrobial therapy associated with increased CD infection risk decreased by 41% during the period 2003–2005 (P < .001). The aggregate rate of CD infection during the period 2001–2006 decreased to 4.8 infections per 1000 HDs (odds ratio, 2.2; 95% confidence interval, 1.4–3.1; P < .001) and by 2006, was 3.0 infections per 1000 HDs, a rate reduction of 71% (odds ratio, 3.5; 95% confidence interval, 2.3–5.4; P < .001). During the period 2000–2001, the proportion of severe CD cases peaked at 9.4% (37 of 393 CD infections were severe); the rate decreased to 3.1% in 2002 and further decreased to 1.0% in 2006—a 78% overall reduction (odds ratio, 20.3; 95% confidence interval, 2.8–148.2; P < .001). In 2005, 13% of CD isolates were type BI (20% were hospital acquired), which represented a significant reduction from 2001 (P < .001). Conclusions. The outbreak of CD infection with the BI strain in our hospital was controlled after implementing a CD infection control "bundle." Early identification, coupled with appropriate control measures, reduces the rate of CD infection and the frequency of adverse events.
•We developed recommendations for DTC surveillance in CAYAC survivors.•At-risk survivors should be counseled about options for DTC surveillance.•It is recommended to use palpation or ultrasonography ...as a screening modality.•Consultation with a thyroid specialist is recommended for survivors with a thyroid nodule.
Radiation exposure to the thyroid gland during treatment of childhood, adolescent and young adult cancer (CAYAC) may cause differentiated thyroid cancer (DTC). Surveillance recommendations for DTC vary considerably, causing uncertainty about optimum screening practices. The International Late Effects of Childhood Cancer Guideline Harmonization Group, in collaboration with the PanCareSurFup Consortium, developed consensus recommendations for thyroid cancer surveillance in CAYAC survivors. These recommendations were developed by an international multidisciplinary panel that included 33 experts in relevant medical specialties who used a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. Of the two available surveillance strategies, thyroid ultrasound and neck palpation, neither was shown to be superior. Consequently, a decision aid was formulated to guide the health care provider in counseling the survivor. The recommendations highlight the need for shared decision making regarding whether to undergo surveillance for DTC and in the choice of surveillance modality.
Aim
The Helping Babies Breathe (HBB) programme is known to decrease neonatal mortality in low‐resource settings but gaps in care still exist. This study describes the use of quality improvement to ...sustain gains in birth asphyxia‐related mortality after HBB.
Methods
Tenwek Hospital, a rural referral hospital in Kenya, identified high rates of birth asphyxia (BA). They developed a goal to decrease the suspected hypoxic‐ischaemic encephalopathy (SHIE) rate by 50% within six months after HBB. Rapid cycles of change were used to test interventions including training, retention and engagement for staff/trainees and improved data collection. Run charts followed the rate over time, and chi‐square analysis was used.
Results
Ninety‐six providers received HBB from September to November 2014. Over 4000 delivery records were reviewed. Ten months of baseline data showed a median SHIE rate of 14.7/1000 live births (LB) with wide variability. Ten months post‐HBB, the SHIE rate decreased by 53% to 7.1/1000 LB (p = 0.01). SHIE rates increased after initial decline; investigation determined that half the trained midwives had been transferred. Presenting data to administration resulted in staff retention. Rates have after remained above goal with narrowing control limits.
Conclusion
Focused quality improvement can sustain and advance gains in neonatal outcomes post‐HBB training.
The abscisic acid (ABA)-induced protein kinase PKABA1 is present in dormant seeds and is a component of the signal transduction pathway leading to ABA-suppressed gene expression in cereal grains. We ...have identified a member of the ABA response element-binding factor (ABF) family of basic leucine zipper transcription factors from wheat (Triticum aestivum) that is specifically bound by PKABA1. This protein (TaABF) has highest sequence similarity to the Arabidopsis ABA response protein AB15. In two-hybrid assays TaABF bound only to PKABA1, but not to a mutant version of PKABA1 lacking the nucleotide binding domain, suggesting that binding of TaABF requires prior binding of ATP as would be expected for binding of a protein substrate by a protein kinase. TaABF mRNA accumulated together with PKABA1 mRNA during wheat grain maturation and dormancy acquisition and TaABF transcripts increased transiently during imbibition of dormant grains. In contrast to PKABA1 mRNA, TaABF mRNA is seed specific and did not accumulate in vegetative tissues in response to stress or ABA application. PKABA1 produced in transformed cell lines was able to phosphorylate synthetic peptides representing three specific regions of TaABF. These data suggest that TaABF may serve as a physiological substrate for PKABA1 in the ABA signal transduction pathway during grain maturation, dormancy expression, and ABA-suppressed gene expression.
Environmental DNA analyses of fungal communities typically reveal a much larger diversity than can be ascribed to known species. Much of this hidden diversity lies within undescribed fungal lineages, ...especially the early diverging fungi (EDF). Although these EDF often represent new lineages even at the phylum level, they have never been cultured, making their morphology and ecology uncertain. One of the methods to characterize these uncultured fungi is a single-cell DNA sequencing approach. In this study, we established a large data set of single-cell sequences of EDF by manually isolating and photographing parasitic fungi on various hosts such as algae, protists, and micro-invertebrates, combined with subsequent long-read sequencing of the ribosomal DNA locus (rDNA). We successfully obtained rDNA sequences of 127 parasitic fungal cells, which clustered into 71 phylogenetic lineages belonging to seven phylum-level clades of EDF: Blastocladiomycota, Chytridiomycota, Aphelidiomycota, Rozellomycota, and three unknown phylum-level clades. Most of our single cells yielded novel sequences distinguished from both described taxa and existing metabarcoding data, indicating an expansive and hidden diversity of parasitic taxa of EDF. We also revealed an unexpected diversity of endobiotic
-like chytrids and hyper-parasitic lineages. Overall, by combining photographs of parasitic fungi with phylogenetic analyses, we were able to better understand the ecological function and morphology of many of the branches on the fungal tree of life known only from DNA sequences. IMPORTANCE Much of the diversity of microbes from natural habitats, such as soil and freshwater, comprise species and lineages that have never been isolated into pure culture. In part, this stems from a bias of culturing in favor of saprotrophic microbes over the myriad symbiotic ones that include parasitic and mutualistic relationships with other taxa. In the present study, we aimed to shed light on the ecological function and morphology of the many undescribed lineages of aquatic fungi by individually isolating and sequencing molecular barcodes from 127 cells of host-associated fungi using single-cell sequencing. By adding these sequences and their photographs into the fungal tree, we were able to understand the morphology of reproductive and vegetative structures of these novel fungi and to provide a hypothesized ecological function for them. These individual host-fungal cells revealed themselves to be complex environments despite their small size; numerous samples were hyper-parasitized with other zoosporic fungal lineages such as Rozellomycota.
Background: Researchers are currently discussing the need for consensus on a core set of outcome measures to assess interventions in aphasia. For indirect, environmental approaches to aphasia ...intervention, such as communication partner training (CPT), the roadmap to obtaining consensus on core outcome measures seems especially complex. While the purpose of CPT is to improve communication for people with communication disorders, the intervention is aimed at the communication partner. There is also a variety of goals, activities, and possible settings for CPT. This complexity increases the risk of a mismatch between the goals and content of the intervention and measures used to evaluate the outcome.
Aims: The purpose of this paper is to describe the complexity of measuring outcomes from CPT. The aim is to enable clinicians and researchers to reflect on the outcomes to be measured and also on how different types of measures may or may not be aligned with the goals and content of a specific CPT intervention.
Main contribution: The current proliferation of outcome measures used in CPT is considered in the light of a survey of general factors to be considered in evaluating intervention outcomes. The complexity of measuring outcomes in CPT is illustrated and the importance of alignment of main objectives, intervention tasks, and projected outcomes is exemplified by referencing two common types of CPT approaches. Objectives relating to knowledge of aphasia, interactional behaviour, and feelings and attitudes are considered in relation to specific outcome measurements. It is suggested that both study-specific and more general measures are needed for capturing and comparing outcomes. The measurement of relevant outcome in CPT is discussed along with implications for future research and clinical practice.
Conclusions: Different CPT approaches share the same purpose of facilitating communication in aphasia, but their application in research studies or in the clinic, is specific to the particular context. Special care must thus be taken in both clinical practice and research to safeguard the alignment between objectives, tasks, and projected intervention outcomes and the actual measures used. Further, it is concluded that there is a need for the development of new measures based on a consensus on key outcomes to be measured in CPT.
Background & Aims: Postoperative ileus is a poorly understood and common problem. We previously demonstrated an association between a suppression in jejunal circular muscle activity and a massive ...extravasation of leukocytes into the muscularis after surgical manipulation of the small bowel. This study was pursued to establish a direct causal link between these events. Methods: Reverse-transcription polymerase chain reaction and immunohistochemistry were used to detect and localize expression of adhesion molecules: P-selectin, intercellular adhesion molecule 1 (ICAM-1), and lymphocyte function–associated antigen 1 (LFA-1). Leukocyte infiltration and in vitro jejunal circular muscle function were quantified in controls and manipulated animals with and without antibody treatment (1A29, WT.1, and WT.3). Results: Surgical manipulation caused a significant up-regulation within the muscularis of ICAM-1 and P-selectin messenger RNA. ICAM-1 and P-selectin protein expression was increased within the muscularis microvasculature, and ICAM-1 and LFA-1 were expressed on infiltrating cells. Administration of adhesion molecule antibodies prevented the recruitment of monocytes and neutrophils into the muscularis and also averted jejunal circular muscle dysfunction. Conclusions: The data demonstrate that adhesion molecule antibodies prevent surgically induced suppression of intestinal muscle contractions and therefore suggests that late postoperative ileus is mediated through a leukocytic inflammatory response within the intestinal muscularis externa.
We have searched the Arabidopsis and rice (Oryza sativa) genomes for homologs of LRX1, an Arabidopsis gene encoding a novel type of cell wall protein containing a leucine-rich repeat (LRR) and an ...extensin domain. Eleven and eight LRX (LRR/EXTENSIN) genes have been identified in these two plant species, respectively. The LRX gene family encodes proteins characterized by a short N-terminal domain, a domain with 10 LRRs, a cysteine-rich motif, and a variable C-terminal extensin-like domain. Phylogenetic analysis performed on the conserved domains indicates the existence of two major clades of LRX proteins that arose before the eudicot/monocot divergence and then diversified independently in each lineage. In Arabidopsis, gene expression studies by northern hybridization and promoter::uidA fusions showed that the two phylogenetic clades represent a specialization into "reproductive" and "vegetative" LRXs. The four Arabidopsis genes of the "reproductive" clade are specifically expressed in pollen, whereas the seven "vegetative" genes are predominantly expressed in various sporophytic tissues. This separation into two expression classes is also supported by previous studies on maize (Zea mays) and tomato (Lycopersicon esculentum) LRX homologs and by information on available rice ESTs. The strong conservation of the amino acids responsible for the putative recognition specificity of the LRR domain throughout the family suggests that the LRX proteins interact with similar ligands.
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