Search

Hasan reads the poems as a 'picture of an inept state, one in which the king and his officials are reckless and indifferent and there is a total breakdown of law and order' (p. 75). Hasan notes that although two witnesses were required for property deeds, documents often bear a much larger, and quite heterogeneous, list of witnesses. [Extracted from the article]

The article offers information about the post-colonial archives, along with explores how they reveal the mobilities of usage and collecting practices.

Indian magazines and print culture in general have been studied more thoroughly for the colonial period, but the 1950s–1970s have rightly been called the golden age of magazine culture. In Hindi literary lore, magazines loom large as the main platform for literature, where poets and fiction writers found readers and recognition and critics debated aesthetics and ideology. To borrow Amit Chaudhuri's phrase, magazines were sites of intense 'literary activism': an activism by editors on behalf of literature to champion new writers and encourage readers' tastes, but also a constant critical interrogation on the value and function of literature. Despite their ephemeral nature—particularly in the Hindi context where old books and periodicals tend to be sold in bulk as scrap paper—magazines embody, and capture for us eager after-readers, a lively community of readers and writers. This essay explores the multilingual 'ecology' of Hindi and English literary and middlebrow magazines, including Kahānī, Kalpanā, Sārikā, Saritā and Caravan. [ABSTRACT FROM AUTHOR]

Aim: Pain associated with immunisations can result in distress and/or anxiety for children and parents. We assessed the feasibility and acceptability of two novel devices; Coolsense (cold) and Buzzy (vibration ± cooling pads) versus standard care to minimise pain during immunisations. We also evaluated compliance to the devices and parent's perception of the effectiveness of the devices/standard care for minimising pain during immunisation.Design: Open label, pilot, randomised controlled trial (RCT).Methods: Forty children aged 3.5 to 6 years attending an Immunisation Centre at The Royal Children's Hospital in Melbourne, Australia, were randomised (1:1:1:1) into four groups: (i) Coolsense plus standard care; (ii) Buzzy with cold plus standard care; (iii) Buzzy without cold plus standard care; and (iv) Standard care alone (distraction with bubbles).Results and Analysis: Recruitment was completed in 12 days. Seventy percent were compliant with Buzzy (±cold), 82% with Coolsense, and 60% with standard care. Buzzy (with cold) was identified as effective by 70% of parents, Coolsense by 64%, Buzzy without cold by 50% and standard care by 60%.Conclusions: This pilot study demonstrated feasibility. A larger RCT is needed to provide definitive evidence to inform best practice for minimising immunisation pain in young children. [ABSTRACT FROM AUTHOR]

More books from India in Indian languages circulated in Europe in the nineteenth century than now – partly thanks to the efforts of book importers like Trübner & Co. Trübner's monthly American & Oriental Literary Record (1865–) shows pages and pages of imported Sanskrit books, but also books in Hindi, Hindustani, Bengali, Marathi, Telugu, Gujarati, Arabic, Persian, and so on. Trübner also imported Peruvian, Argentinian, Brazilian, Yucatanese and other books from Latin America. Yet this impressive circulation and presence of books did not translate into their recognition as world literature. Voluminous compendia like John Macy's The Story of World Literature (1927) cover "Asian Literature" in merely thirteen pages (out of five hundred), and fail to mention any modern Indian writer apart from Rabindranath Tagore, damning him with faint praise. Why was this material presence and circulation of books in non-European languages in Britain and other parts of Europe matched by their absence as modern literary texts from the imagination of world literature? This essay examines the "technologies of recognition" (Shih) that made modern Indian literatures virtually invisible though materially present in Europe, and the conditions of visibility that occasionally allowed them to be seen. [ABSTRACT FROM AUTHOR]

HPTLC silica gel, amino and C18 plates in combination with different developing solvents were explored for the first HPTLC chemical profiles of flavonoids and sugars in crude extracts from leaves and fruits of caigua (Cyclanthera pedata Scrabs) harvested in Slovenia and Italy. New HPTLC and HPTLC-MS methods for analyses of flavonoids are based on HPTLC silica gel (preconditioned with water) or C18 plates in combination with developing solvents ethyl acetate–water–formic acid (17:3:2, v/v) or 5% formic acid in methanol-water (7:3, v/v), respectively. Detection was performed before (for flavonoids) and/or after post-chromatographic derivatization with Natural product (NP) reagent for flavonoids and diphenylamine-aniline-phosphoric acid (DAP) reagent for sugars. HPTLC–MS/(MSn) analyses on silica gel and C18 stationary phases enabled tentative identification of several compounds in crude extracts from leaves and fruits. HPTLC-DPPH• assay combined with image analyses and HPTLC–MS/(MSn) analyses, applied for direct screening of antioxidant activity of separated chromatographic zones (compounds) on HPTLC silica gel plates, confirmed activity in several zones of all crude extracts, in which some active compounds were tentatively identified. Apigenin 6-C-glucoside (isovitexin) and luteolin 8-C-glucoside (orientin) were found in all crude extracts, but the last was the most active free radical scavenger. Both compounds were also identified in dietary supplement product produced from caigua fruits. Crude extracts from leaves showed much higher antioxidant activity than those from fruits. The highest antioxidant activity was determined for crude extract from leaves harvested in Slovenia, while among crude extract from fruits the highest activity was determined for the extract from fruits harvested in Italy. [ABSTRACT FROM AUTHOR]

Analytical separation techniques based on the differential migration velocities of analytes under the action of an electric fi eld are gaining increasing acceptance for the analysis of phenolic compounds in edible and medicinal plants and in plant-derived food products. In Part 2 of this review article the authors discuss the fundamental principles and practical aspects of electromigration techniques, including capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC), and capillary electrochromatography (CEC). The development of two-dimensional systems, performed by coupling either liquid chromatography (LC) with an electromigration technique or two electromigration techniques, operated under different separation mechanisms, is also discussed. [ABSTRACT FROM AUTHOR]

Column-based liquid phase separation techniques, such as liquid chromatography (LC) in reversed phase separation mode and capillary electromigration techniques, using continuous electrolyte systems, are widely used for the identifi cation and quantifi cation of phenolic compounds in plants and food matrices of plant origin. This paper is the fi rst of a two-part review article discussing fundamental and practical aspects of both LC and capillary electromigration techniques used for the analysis of phenolic compounds occurring in plant-derived food and in edible and medicinal plants. The chemical structure and distribution of the major phenolic compounds occurring in the plant kingdom, as well as the main methods used for their extraction and sample preparation, are also discussed. Part 1 will focus on liquid chromatography. [ABSTRACT FROM AUTHOR]

Key Points: Question: For preterm infants with respiratory distress syndrome supported with continuous positive airway pressure (CPAP), does administration of surfactant via a thin catheter improve survival without moderate to severe neurodevelopmental disability (NDD) at 2 years of age compared with sham treatment? Findings: In this follow-up of a randomized clinical trial of 486 infants at 25 to 28 weeks' gestation, the composite outcome of death or NDD at 2 years of age occurred in 36.3% receiving minimally invasive surfactant therapy compared with 36.1% receiving sham treatment. Meaning: In preterm infants supported with CPAP, minimally invasive surfactant therapy did not lead to a reduction in the composite outcome of death or neurodevelopmental disability at 2 years of age. Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, −7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943 This follow-up study of a randomized clinical trial examines the effect of minimally invasive surfactant therapy, surfactant administration via a thin catheter, on death or neurodevelopmental disability at 2 years' corrected age. [ABSTRACT FROM AUTHOR]

An essay is presented on the factors affecting world literature focusing on literacy, manuscript, and access to language. It offers the position of literary critic Franco Moretti on the organization of literature found in core, periphery, and semi-periphery, while author David Damrosch emphasizes circulation. The author also focuses on the literary culture in Uttar Pradesh, India, and examines the relationship between the local and global language.

The story of print and religious publics in colonial India has largely been told as one of reformist groups and religious polemics. But this covers only a small part of the story of religious print, which extends well beyond reformist groups. This essay focuses on the most systematic and long-lived project of publishingsantorature (bani), theSantbānī Pustakmālāof the Belvedere Press, Allahabad. It examines its scope, aims and methods as well as its religious orientation and conceptualisation of a religious-devotional public in early-twentieth-century North India. Halfway between oralbhajangroups and the scholarly publications of the collected works (granthavali) ofsantpoets, throughout the twentieth century the Belvedere Press booklets have commanded tremendous currency as religious print-objects in the Hindi devotional public sphere. The results of one publisher's effort and investment, and of significant reorganisation of material from manuscript sources, these booklets have been extremely popular and lasting products in the extensive market for religious material, clearly a crucial technology for individual and group religious practice (bhajan), before which the lineages' own publishing efforts pale into quasi-insignificance. [ABSTRACT FROM PUBLISHER]

After over a century of language nationalism and almost as long a period of intense competition and mutual contempt, in post-liberalisation and post-low caste assertion India the boundaries between English and Hindi have recently become more porous, and the hold of both ‘pure Hindi’ and ‘British/pure English’ has become much more limited. English is of course still the language of greater opportunities in local and global terms, and increasingly so, but as low-caste politicisation and literacy widen the sphere of Hindi, and the ‘new middle class’ remains resolutely bilingual in its everyday and entertainment practices, the relation between English and Hindi has become more a relationship of parallel expansion, though still perceived in public discourse as a zero-sum game. [ABSTRACT FROM PUBLISHER]

Objectives: To compare the frequency of headache and the procedure time following lumbar puncture (LP) using a 25-gauge needle compared to a 22-gauge needle. Design: 4-period crossover blinded randomised controlled trial. Setting: Oncology unit, Royal Children's Hospital, Melbourne. Patients: Children aged 4-15 years at enrolment having LPs as part of their treatment for leukaemia. Interventions: Each child was allocated a random sequence of four LPs, two with a 22-gauge and two with a 25-gauge needle. Outcome measures: The presence of post-LP headache. Secondary outcomes included the presence of any headache, procedure time and impact of headache on the family. Results: Data on 341 procedures in 93 randomised children were analysed. There was little difference in the incidence of post-LP headache between the two needle sizes (22-gauge 7.2%, 95% CI 3.8 to 12.2; 25-gauge 4.6%, 95% CI 2.0 to 8.9, p=0.3) or in the incidence of any headache (22-gauge 18% 95% CI 12.5 to 24.6; 25-gauge 15%, 95% CI 10.0 to 21.1, p=0.4). Use of the 25-gauge needle was associated with longer procedure times. The incidence of post-LP headache showed little evidence of an age effect (OR =1.1, 95% CI 0.98 to 1.3) and was higher in girls than in boys (11% vs 3%, respectively, OR=3.3, 95% CI 1.3 to 8.4, p=0.014). Fifty-five per cent of families with a child with a post-LP headache assessed the overall functional impact as moderate or severe. Conclusions: There was little difference in the occurrence of post-LP headache or any headache between procedures carried out using the 22-gauge or 25-gauge needles. Depending on the circumstances of the procedure and the experience of the operator, either gauge may be appropriate for an LP in a child. [ABSTRACT FROM AUTHOR]

This special issue collects a series of essays that reimagine the positioning of translation as theory and practice in diverse postcolonial contexts. A rethinking of translation as a linguistic transaction which always necessarily involves a negotiation between cultures has been at the core of postcolonial theory almost since its inception. Much of the discussion of translation in relation to imperial formations has centred around the notion that translation between languages involves unequal power relations. English or French, as (post)imperial languages, are seen as inherently dominant in the postcolonial literary landscape. Thus translation is used as a powerful metaphor to evoke the complex economies of cultural exchange that take place under the sign of empire. These essays broaden the scope of postcolonial translation to include postcolonial multilingual contexts that necessitate constant translation and self-translation within their boundaries, though not always to one's benefit. [ABSTRACT FROM PUBLISHER]

p66Shc promotes apoptosis and controls the intracellular redox balance. A fraction of p66Shc exists within mitochondria, where it oxidizes cytochrome c to form hydrogen peroxide, which in turn induces mitochondrial permeability and apoptosis. However, cells tolerate p66Shc expression and accumulate oxidative damage under normal conditions, implying that the p66Shc functions must be tightly regulated. Here we review available knowledge on the regulation of p66Shc transcription, protein stabilization and post-translational modifications. In addition, we report novel investigations into the role of the mitochondrial import machinery on p66Shc activation, which highlight the energetic status of mitochondria as a crucial determinant of p66Shc function. [ABSTRACT FROM AUTHOR]

Written in October 2001 as a ‘gut reaction’ to the attack on the Twin Towers, and published first as a long article in the daily Corriere della Sera and then in book form (in its original shape, twice as long as the article) in December 2001, Oriana Fallaci's pamphlet La rabbia e l'orgoglio (‘Anger and pride’) was in its twenty-sixth edition when I bought it in September 2004. Its follow-up, La forza della ragione (‘The force of reason’), has already sold 800,000 copies since its publication in 2004. Oriana Fallaci has emerged after 9/11 as the strongest and most vocal Italian representative of the ‘clash of civilizations’ theory. This essay analyses the constitutive elements of her discourse (Italian nationalism, values instead of history and politics, and violent speech conflating Islam, terrorism and immigrants) and tries to understand its appeal and the sources of its authority in Fallaci's career, in order to outline the specific Italian version of the clash of civilizations theory. [ABSTRACT FROM AUTHOR]

P66Shc regulates life span in mammals and is a critical component of the apoptotic response to oxidative stress. It functions as a downstream target of the tumor suppressor p53 and is indispensable for the ability of oxidative stress-activated p53 to induce apoptosis. The molecular mechanisms underlying the apoptogenic effect of p66Shc are unknown. Here we report the following three findings. (i) The apoptosome can be properly activated in vitro in the absence of p66Shc only if purified cytochrome c is supplied. (ii) Cytochrome c release after oxidative signals is impaired in the absence of p66Shc. (iii) p66Shc induces the collapse of the mitochondrial trans-membrane potential after oxidative stress. Furthermore, we showed that a fraction of cytosolic p66Shc localizes within mitochondria where it forms a complex with mitochondrial Hsp70. Treatment of cells with ultraviolet radiation induced the dissociation of this complex and the release of monomeric p66Shc. We propose that p66Shc regulates the mitochondrial pathway of apoptosis by inducing mitochondrial damage after dissociation from an inhibitory protein complex. Genetic and biochemical evo idence suggests that mitochondria regulate life span through their effects on the energetic metabolism (mitochondrial theory of aging). Our data suggest that mitochondrial regulation of apoptosis might also contribute to life span determination. [ABSTRACT FROM AUTHOR]

Focuses on the different meanings of love in Cambridge, England. Introduction of elements on heterogeneity; Use of traditional idioms; Relation between culture and courtliness.

Reveals the gap between received versions of Indian literature in the West and the varieties of form and language in India itself. Predomination of nuance, ellipsis and the exploration of realist boundaries; Comparison between Hindi epics and the postmodern novel; Government subsidies for Hindi literary publishing.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain.Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD).Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020.Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met.Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately.Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group.Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded.Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943. [ABSTRACT FROM AUTHOR]

Background: Outpatient parenteral antimicrobial therapy in children is common despite no evidence of its efficacy or safety from clinical trials. We aimed to compare the efficacy and safety of intravenous antibiotic therapy at home with that of standard treatment in hospital for children with moderate to severe cellulitis.Methods: The Cellulitis at Home or Inpatient in Children from the Emergency Department (CHOICE) trial was a randomised, controlled, non-inferiority trial in children aged 6 months to 18 years who presented to the emergency department at The Royal Children's Hospital (Melbourne, VIC, Australia) with uncomplicated moderate to severe cellulitis. Participants were randomly assigned to receive either intravenous ceftriaxone (50 mg/kg once daily) at home or intravenous flucloxacillin (50 mg/kg every 6 h) in hospital with web-based randomisation, stratified by age and periorbital cellulitis. The primary outcome was treatment failure, which was defined as no clinical improvement or occurrence of an adverse event, resulting in a change in empiric antibiotics within 48 h of the first dose. Secondary outcomes included adverse events and acquisition of antibiotic-resistant bacteria. Outcomes were assessed in all randomised participants with outcome data (intention-to-treat population) and in all individuals who received treatment as allocated and did not have any major protocol violations (per-protocol population). For home treatment to be non-inferior to hospital treatment, the difference between groups in the proportion of children with treatment failure in the intention-to-treat population had to be less than 15%. This trial is registered with ClinicalTrials.gov, number NCT02334124.Findings: Between Jan 9, 2015, and June 15, 2017, we screened 1135 children for eligibility, of whom 190 were randomly assigned to receive ceftriaxone at home (n=95) or flucloxacillin in hospital (n=95). The intention-to-treat analysis comprised 188 children (93 in the home group and 95 in the hospital group) because two children in the home group were found to be ineligible after randomisation and were excluded. Treatment failure occurred in two (2%) children in the home group and in seven (7%) children in the hospital group (risk difference -5·2%, 95% CI -11·3 to 0·8, p=0·088). In the per-protocol analysis, treatment failure occurred in one (1%) of 89 children in the home group and in seven (8%) of 91 children in the hospital group (-6·5%, -12·4 to -0·7). Fewer children treated at home than in hospital had an adverse event (two [2%] vs ten [11%]; p=0·048). There was no difference between groups in rates of nasal acquisition of meticillin-resistant Staphylococcus aureus or gastrointestinal acquisition of extended-spectrum β-lactamase-producing bacteria or Clostridium difficile after 3 months.Interpretation: Home treatment with intravenous ceftriaxone is not inferior to treatment in hospital with intravenous flucloxacillin for children with cellulitis. The standard of care for the intravenous treatment of uncomplicated cellulitis in children should be home or outpatient care when feasible.Funding: The Royal Children's Hospital Foundation and Murdoch Children's Research Institute. [ABSTRACT FROM AUTHOR]

To investigate the effects of providing rigid wrist-hand orthoses plus usual multidisciplinary care, on reducing hand impairments in children with cerebral palsy. A pragmatic, multicentre, assessor-blinded randomised controlled trial aimed to enrol 194 children aged 5–15 years, with wrist flexor Modified Ashworth Scale score ≥1. Randomisation with concealed allocation was stratified by study site and passive wrist range. The treatment group received a rigid wrist-hand orthosis, to wear ≥6 h per night for 3 years. Analysis included repeated measures mixed-effects linear regression models, using intention-to-treat principles. The trial stopped early due to insufficient recruitment: 74 children, across all Manual Ability Classification System levels, were randomised (n = 38 orthosis group; n = 36 control). Mean age was 10.2 (SD 3.1) years (orthosis group) and 9.1 (SD 2.8) years (control). Data showed some evidence that rigid wrist-hand orthosis impacted passive wrist extension with fingers extended in the first year [mean difference between-groups at 6 months: 13.15° (95%CI: 0.81–25.48°, p = 0.04); 12 months: 20.94° (95%CI: 8.20–33.69°, p = 0.001)]. Beyond 18 months, participant numbers were insufficient for conclusive findings. The study provided detailed data about short- and long-term effects of the wrist-hand orthosis and highlighted challenges in conducting large randomised controlled trials with this population. Trial Registration: Australia and New Zealand Clinical Trials Registry: U1111-1164-0572 There may be incremental benefit, for children with cerebral palsy, at 6 and 12 months on passive wrist range from wearing a rigid wrist-hand orthosis designed according to this protocol. The rigid-wrist-hand orthosis evaluated in this study, which allowed for some tailoring for individual children's presentations, differed in design from past recommendations for "resting hand" positioning. Longitudinal follow up of children with cerebral palsy prescribed a rigid wrist-hand orthosis is essential to monitor any benefit. Minor adverse events were commonly experienced when wearing the orthosis and should be discussed prior to prescription of a rigid wrist-hand orthosis. [ABSTRACT FROM AUTHOR]

In this paper we present a definition of the widespread problem of chronic pain and the contribution of Biofeedback procedures to the improvement of its clinical conditions, with brief reference to some explanatory models. Subsequently, an up-to-date review of Biofeedback's various clinical treatment applications is performed based on the Efficiency Criteria of the International Guidelines proposed by the Association for Applied Psychophysiology and Biofeedback for the treatment of chronic pain. Biofeedback results in a range of «specific efficacy» to one of «possible efficacy» for most of the clinical pathologies considered. [ABSTRACT FROM AUTHOR]

Objectives: Nurse home visiting (NHV) is widely implemented to address inequities in child and maternal health. However, few studies have examined longer-term effectiveness or delivery within universal healthcare systems. We evaluated the benefits of an Australian NHV program ("right@home") in promoting children's language and learning, general and mental health, maternal mental health and wellbeing, parenting and family relationships, at child ages 4 and 5 years. Setting and participants: Randomised controlled trial of NHV delivered via universal, child and family health services (the comparator). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states (Victoria, Tasmania) in Australia. Intervention: Mothers in the intervention arm were offered 25 nurse home visits (mean 23·2 home visits [SD 7·4, range 1–43] received) of 60–90 minutes, commencing antenatally and continuing until children's second birthdays. Primary and secondary outcomes measured: At 4 and 5 years, outcomes were assessed via parent interview and direct assessment of children's language and learning (receptive and expressive language, phonological awareness, attention, and executive function). Outcomes were compared between intervention and usual care arms (intention to treat) using adjusted regression with robust estimation to account for nurse/site. Missing data were addressed using multiple imputation and inverse probability weighting. Results: Of 722 women enrolled in the trial, 225 of 363 (62%) intervention and 201 of 359 (56%) usual care women provided data at 5 years. Estimated group differences showed an overall pattern favouring the intervention. Statistical evidence of benefits was found across child and maternal mental health and wellbeing, parenting and family relationships with effect sizes ranging 0·01–0·27. Conclusion: An Australian NHV program promoted longer-term family functioning and wellbeing for women experiencing adversity. NHV can offer an important component of a proportionate universal system that delivers support and intervention relative to need. Trial registration: 2013–2016, registration ISRCTN89962120 [ABSTRACT FROM AUTHOR]

Background: A high proportion of patients with neurofibromatosis type 1 (NF1) present with functional hearing deficiency as a result of neural abnormality in the late auditory brainstem. Methods: In this randomized, two-period crossover study, we investigated the hypothesis that remote-microphone listening devices can ameliorate hearing and communication deficits in affected school-aged children (7–17 years). Speech perception ability in background noise was evaluated in device-active and inactive conditions using the CNC-word test. Participants were then randomized to one of two treatment sequences: (1) inactive device for two weeks (placebo), followed by active device use for two weeks, or (2) active device for 2 weeks, followed by inactive device for 2 weeks. Listening and communication ratings (LIFE-R Questionnaire) were obtained at baseline and at the end of each treatment phase. Results: Each participant demonstrated functional hearing benefits with remote-microphone use. All showed a speech perception in noise increase when the device was activated with a mean phoneme-score difference of 16.4% (p < 0.001) and reported improved listening/communication abilities in the school classroom (mean difference: 23.4%; p = 0.017). Discussion: Conventional hearing aids are typically ineffective as a treatment for auditory neural dysfunction, making sounds louder, but not clearer for affected individuals. In this study, we demonstrate that remote-microphone technologies are acceptable/tolerable in pediatric patients with NF1 and can ameliorate their hearing deficits. Conclusion: Remote-microphone listening systems offer a viable treatment option for children with auditory deficits associated with NF1. [ABSTRACT FROM AUTHOR]

Background: Understanding how and why de-implementation of low-value practices is sustained remains unclear. The Paediatric Research in Emergency Departments International CollaboraTive (PREDICT) Bronchiolitis Knowledge Translation (KT) Study was a cluster randomised controlled trial conducted in 26 Australian and New Zealand hospitals (May-November 2017). Results showed targeted, theory-informed interventions (clinical leads, stakeholder meetings, train-the-trainer workshop, targeted educational package, audit/feedback) were effective at reducing use of five low-value practices for bronchiolitis (salbutamol, glucocorticoids, antibiotics, adrenaline and chest x-ray) by 14.1% in acute care settings. The primary aim of this study is to determine the sustainability (continued receipt of benefits) of these outcomes at intervention hospitals two-years after the removal of study supports. Secondary aims are to determine sustainability at one-year after removal of study support at intervention hospitals; improvements one-and-two years at control hospitals; and explore factors that influence sustainability at intervention hospitals and contribute to improvements at control hospitals.Methods: A mixed-methods study design. The quantitative component is a retrospective medical record audit of bronchiolitis management within 24 hours of emergency department (ED) presentations at 26 Australian (n = 20) and New Zealand (n = 6) hospitals, which participated in the PREDICT Bronchiolitis KT Study. Data for a total of 1800 infants from intervention and control sites (up to 150 per site) will be collected to determine if improvements (i.e., no use of all five low-value practices) were sustained two- years (2019) post-trial (primary outcome; composite score); and a further 1800 infants from intervention and control sites will be collected to determine sustained improvements one- year (2018) post-trial (secondary outcome). An a priori definition of sustainability will be used. The qualitative component will consist of semi-structured interviews with three to five key emergency department and paediatric inpatient medical and nursing staff per site (total n = 78-130). Factors that may have contributed to sustaining outcomes and/or interventions will be explored and mapped to an established sustainability framework.Discussion: This study will improve our understanding of the sustainability of evidence-based bronchiolitis management in infants. Results will also advance implementation science research by informing future de-implementation strategies to reduce low-value practices and sustain practice change in paediatric acute care.Trial Registration: Australian and New Zealand Clinical Trials Registry No: ACTRN12621001287820. [ABSTRACT FROM AUTHOR]

Background Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid-spare or facilitate earlier extubation in postoperative neonates is unquantified. Objective This randomized placebo-controlled trial aimed to assess whether tramadol's addition to standard analgesia resulted in earlier extubation or reduced analgesic/sedative requirements in postsurgical neonates. Methods Neonates born ≥32 weeks postmenstrual age received either tramadol [T] 2 mg·kg−1 or placebo [P] 6-hourly for up to 5 days postthoracoabdominal surgery in addition to morphine (commenced at 20 mcg·kg−1·h−1) and 6-hourly IV acetaminophen. Time to extubation, morphine and midazolam amounts, hourly pain scores, and seizure activity were compared using an intention-to-treat and per-protocol analysis. Results Seventy-one neonates participated. Median survival time to extubation was similar between the groups (T 67 h [95% CI 51, 84] vs P 52 h [95% CI 43, 65]; P = 0.4), and similar numbers were extubated by 96 h (T 69% vs P 77%; difference −8%, 95% CI −28, 13%). Morphine and midazolam exposure was similar, with low pain scores in both groups (mean percentage of time with a pain score >5/20 during the 5 days: T 13% vs P 11%, difference in means 2.8 [95% CI −1.8, 7.6], P = 0.20). Most participants had normal cranial ultrasounds (T 86% vs P 86%); no seizures occurred clinically or electroencephalographically. Conclusion Tramadol's addition to standard analgesia in this small group of postsurgical neonates did not appear to have any positive effect on time to extubation, morphine or midazolam exposure, or pain scores. This questions the benefit of tramadol for postsurgical neonates. Importantly, no seizures occurred in these ill neonates who may potentially be at greater risk of tramadol toxicity compared with adults. [ABSTRACT FROM AUTHOR]

Background: Bronchiolitis is the most common reason for hospitalisation in infants. All international bronchiolitis guidelines recommend supportive care, yet considerable variation in practice continues with infants receiving non-evidence based therapies. We developed six targeted, theory-informed interventions; clinical leads, stakeholder meeting, train-the-trainer, education delivery, other educational materials, and audit and feedback. A cluster randomised controlled trial (cRCT) found the interventions to be effective in reducing use of five non-evidence based therapies in infants with bronchiolitis. This process evaluation paper aims to determine whether the interventions were implemented as planned (fidelity), explore end-users' perceptions of the interventions and evaluate cRCT outcome data with intervention fidelity data.Methods: A pre-specified mixed-methods process evaluation was conducted alongside the cRCT, guided by frameworks for process evaluation of cRCTs and complex interventions. Quantitative data on the fidelity, dose and reach of interventions were collected from the 13 intervention hospitals during the study and analysed using descriptive statistics. Qualitative data identifying perception and acceptability of interventions were collected from 42 intervention hospital clinical leads on study completion and analysed using thematic analysis.Results: The cRCT found targeted, theory-informed interventions improved bronchiolitis management by 14.1%. The process evaluation data found variability in how the intervention was delivered at the cluster and individual level. Total fidelity scores ranged from 55 to 98% across intervention hospitals (mean = 78%; SD = 13%). Fidelity scores were highest for use of clinical leads (mean = 98%; SD = 7%), and lowest for use of other educational materials (mean = 65%; SD = 19%) and audit and feedback (mean = 65%; SD = 20%). Clinical leads reflected positively about the interventions, with time constraints being the greatest barrier to their use.Conclusion: Our targeted, theory-informed interventions were delivered with moderate fidelity, and were well received by clinical leads. Despite clinical leads experiencing challenges of time constraints, the level of fidelity had a positive effect on successfully de-implementing non-evidence-based care in infants with bronchiolitis. These findings will inform widespread rollout of our bronchiolitis interventions, and guide future practice change in acute care settings.Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415 . [ABSTRACT FROM AUTHOR]

Summary: Reactive oxygen species (ROS) are potent inducers of oxidative damage and have been implicated in the regulation of specific cellular functions, including apoptosis. Mitochondrial ROS increase markedly after proapoptotic signals, though the biological significance and the underlying molecular mechanisms remain undetermined. P66Shc is a genetic determinant of life span in mammals, which regulates ROS metabolism and apoptosis. We report here that p66Shc is a redox enzyme that generates mitochondrial ROS (hydrogen peroxide) as signaling molecules for apoptosis. For this function, p66Shc utilizes reducing equivalents of the mitochondrial electron transfer chain through the oxidation of cytochrome c. Redox-defective mutants of p66Shc are unable to induce mitochondrial ROS generation and swelling in vitro or to mediate mitochondrial apoptosis in vivo. These data demonstrate the existence of alternative redox reactions of the mitochondrial electron transfer chain, which evolved to generate proapoptotic ROS in response to specific stress signals. [Copyright &y& Elsevier]

BACKGROUND: Poor mental health is recognized as one of the greatest global burdens of disease. Maternal mental health is crucial for the optimal health of mothers and their children. We examined the effects of an Australian Nurse Home Visiting (NHV) program (right@home), offered to pregnant women experiencing adversity, on maternal mental health and well-being at child age 3 years. METHODS: A randomized controlled trial of NHV delivered via universal child and family health services (2013-2016). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states. Intervention comprised 25 home visits until child age 2 years. The outcomes assessed 1-year postintervention completion were maternal self-report of mental health symptoms (Depression Anxiety Stress Scales) and positive aspects of mental health (personal well-being and self-efficacy). RESULTS: Of the 722 women enrolled in the trial, 255 of 363 (70%) intervention and 240 of 359 (67%) control group women provided data at 3 years. Compared with controls, the intervention group reported better mental health (reverse Depression Anxiety Stress Scales scores): effect sizes of 0.25 (depression; 95% confidence interval [CI]: 0.08 to 0.32), 0.20 (anxiety; 95% CI: 0.05 to 0.30), 0.17 (stress; 95% CI: 0.09 to 0.37), and 0.23 (total score; 95% CI: 0.12 to 0.38); 0.16 (95% CI: 0.04 to 0.29) for personal well-being; and an odds ratio of 1.60 (95% CI: 1.19 to 2.16) for self-efficacy. CONCLUSIONS: An NHV designed to support mothers experiencing adversity can lead to later maternal mental health benefits, even after the program ends. [ABSTRACT FROM AUTHOR]

Teacher knowledge is a critical factor in student success. In the Classroom Promotion of Oral Language cluster randomized controlled trial, we aimed to determine whether a teacher professional learning intervention focused on promoting oral language led to improved teacher knowledge. We report a study of the impact of professional learning on teacher knowledge of oral language and literacy constructs. The intervention comprised four days of face-to-face professional learning for early years' teachers, and ongoing school implementation support. Teacher knowledge was measured through a survey at baseline, 12 months and 24 months (n = 40 intervention, n = 38 control). Teachers in the intervention arm made more correct responses on survey items than teachers in the control arm, at both time points. The professional learning intervention improved teacher knowledge in the short-to-medium term. [ABSTRACT FROM AUTHOR]

• Both OPV and rotavirus vaccines contain live, attenuated strains that replicate in the gut. • OPV and rotavirus vaccine co-administration has been associated with lower rotavirus immune responses. • RV3-BB is a novel human neonatal rotavirus vaccine that provides protection from rotavirus disease from birth. • OPV and RV3-BB co-administration did not reduce immunogenicity of either vaccine. • These findings support the use of RV3-BB where either OPV or IPV is used in the routine schedule. The RV3-BB human neonatal rotavirus vaccine was developed to provide protection from severe rotavirus disease from birth. The aim of this study was to investigate the potential for mutual interference in the immunogenicity of oral polio vaccine (OPV) and RV3-BB. A randomized, placebo-controlled trial involving 1649 participants was conducted from January 2013 to July 2016 in Central Java and Yogyakarta, Indonesia. Participants received three doses of oral RV3-BB, with the first dose given at 0–5 days (neonatal schedule) or ~8 weeks (infant schedule), or placebo. Two sub-studies assessed the immunogenicity of RV3-BB when co-administered with either trivalent OPV (OPV group, n = 282) or inactivated polio vaccine (IPV group, n = 333). Serum samples were tested for antibodies to poliovirus strains 1, 2 and 3 by neutralization assays following doses 1 and 4 of OPV. Sero-protective rates to poliovirus type 1, 2 or 3 were similar (range 0.96–1.00) after four doses of OPV co-administered with RV3-BB compared with placebo. Serum IgA responses to RV3-BB were similar when co-administered with either OPV or IPV (difference in proportions OPV vs IPV: sIgA responses; neonatal schedule 0.01, 95% CI −0.12 to 0.14; p = 0.847; infant schedule −0.10, 95% CI −0.21 to −0.001; p = 0.046: sIgA GMT ratio: neonatal schedule 1.23, 95% CI 0.71–2.14, p = 0.463 or infant schedule 1.20, 95% CI 0.74–1.96, p = 0.448). The co-administration of OPV with RV3-BB rotavirus vaccine in a birth dose strategy did not reduce the immunogenicity of either vaccine. These findings support the use of a neonatal RV3-BB vaccine where either OPV or IPV is used in the routine vaccination schedule. [ABSTRACT FROM AUTHOR]

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain.Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders.Design, Setting, and Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017.Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks.Main Outcomes and Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables.Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21).Conclusions and Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference.Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Nurse home visiting (NHV) may redress inequities in children's health and development evident by school entry. We tested the effectiveness of an Australian NHV program (right@home), offered to pregnant women experiencing adversity, hypothesizing improvements in (1) parent care, (2) responsivity, and (3) the home learning environment at child age 2 years. METHODS: A randomized controlled trial of NHV delivered via universal child and family health services was conducted. Pregnant women experiencing adversity (>2 of 10 risk factors) with sufficient English proficiency were recruited from antenatal clinics at 10 hospitals across 2 states. The intervention comprised 25 nurse visits to child age 2 years. Researchers blinded to randomization assessed 13 primary outcomes, including Home Observation of the Environment (HOME) Inventory (6 subscales) and 25 secondary outcomes. RESULTS: Of 1427 eligible women, 722 (50.6%o) were randomly assigned; 306 of 363 (84%) women in the intervention and 290 of 359 (81%) women in the control group provided 2-year data. Compared with women in the control group, those in the intervention reported more regular child bedtimes (adjusted odds ratio 1.76; 95% confidence interval [CI] 1.25 to 2.48), increased safety (adjusted mean difference [AMD] 0.22; 95% CI 0.07 to 0.37), increased warm parenting (AMD 0.09; 95% CI 0.02 to 0.16), less hostile parenting (reverse scored; AMD 0.29; 95% CI 0.16 to 0.41), increased HOME parental involvement (AMD 0.26; 95% CI 0.14 to 0.38), and increased HOME variety in experience (AMD 0.20; 95% CI 0.07 to 0.34). CONCLUSIONS: The right@home program improved parenting and home environment determinants of children's health and development. With replicability possible at scale, it could be integrated into Australian child and family health services or trialed in countries with similar child health services. [ABSTRACT FROM AUTHOR]

Background: This paper presents drinking patterns in a prospective study of a population-based cohort of 1570 pregnant women using a combination of dose and timing to give best estimates of prenatal alcohol exposure (PAE). Novel assessments include women's special occasion drinking and alcohol use prior to pregnancy recognition.Methods: Information on up to nine types of alcoholic drink, with separate frequencies and volumes, including drinking on special occasions outside a 'usual' pattern, was collected for the periconceptional period and at four pregnancy time points. Weekly total and maximum alcohol consumption on any one occasion was calculated and categorised. Drinking patterns are described in the context of predictive maternal characteristics.Results: 41.3 % of women did not drink during pregnancy, 27 % drank in first trimester only; most of whom stopped once they realised they were pregnant (87 %). When compared to women who abstained from alcohol when pregnant, those who drank in the first trimester only were more likely to have an unplanned pregnancy and not feel the effects of alcohol quickly. Almost a third of women continued to drink alcohol at some level throughout pregnancy (27 %), around half of whom never drank more than at low or moderate levels. When compared with abstainers and to women who only drank in trimester one, those who drank throughout pregnancy tended to be in their early to mid-thirties, smoke, have a higher income and educational attainment. Overall, almost one in five women (18.5 %) binge drank prior to pregnancy recognition, a third of whom were identified with a question about 'special occasion' drinking. Women whose age at first intoxication was less than 18 years (the legal drinking age in Australia), were significantly more likely to drink in pregnancy and at binge levels prior to pregnancy recognition.Conclusions: We have identified characteristics of pregnant women who either abstain, drink until pregnancy awareness or drink throughout pregnancy. These may assist in targeting strategies to enhance adherence to an abstinence policy and ultimately allow for appropriate follow-up and interpretation of adverse child outcomes. Our methodology also produced important information to reduce misclassification of occasional binge drinking episodes and ensure clearly defined comparison groups. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Data from clinical trials support the use of continuous positive airway pressure (CPAP) for initial respiratory management in preterm infants, but there is concern regarding the potential failure of CPAP support. We aimed to examine the incidence and explore the outcomes of CPAP failure in Australian and New Zealand Neonatal Network data from 2007 to 2013. METHODS: Data from inborn preterm infants managed on CPAP from the outset were analyzed in 2 gestational age ranges (25-28 and 29-32 completed weeks). Outcomes after CPAP failure (need for intubation <72 hours) were compared with those succeeding on CPAP using adjusted odds ratios (AORs). RESULTS: Within the cohort of 19 103 infants, 11 684 were initially managed on CPAP. Failure of CPAP occurred in 863 (43%) of 1989 infants commencing on CPAP at 25-28 weeks' gestation and 2061 (21%) of 9695 at 29-32 weeks. CPAP failure was associated with a substantially higher rate of pneumothorax, and a heightened risk of death, bronchopulmonary dysplasia (BPD) and other morbidities compared with those managed successfully on CPAP. The incidence of death or BPD was also increased: (25-28 weeks: 39% vs 20%, AOR 2.30, 99% confidence interval 1.71-3.10; 29-32 weeks: 12% vs 3.1%, AOR 3.62 [2.76-4.74]). The CPAP failure group had longer durations of respiratory support and hospitalization. CONCLUSIONS: CPAP failure in preterm infants is associated with increased risk of mortality and major morbidities, including BPD. Strategies to promote successful CPAP application should be pursued vigorously. [ABSTRACT FROM AUTHOR]

Aim: To compare diazepam use, muscle spasm, analgesia, and side effects when clonidine or fentanyl are added to epidural bupivacaine in children with cerebral palsy after multilevel orthopaedic surgery.Method: Fifty children were prospectively randomized to receive clonidine (n=24, mean age 10y 10mo [SD 2y 11mo]) or fentanyl (n=26, mean age 10y 11mo [SD 2y 10mo]).Results: There was no difference in primary outcome measures: median diazepam use (fentanyl 0, interquartile range [IQR] 0-0; clonidine 0, IQR 0-0; p=0.46), any muscle spasm (no muscle spasms in: fentanyl, 36%; clonidine, 62%; p=0.11), painful muscle spasm (fentanyl 40%; clonidine 25%; p=0.46), or pain score ≥6 (none: fentanyl 44%; clonidine 42%; p=0.29). There were differences in secondary outcome measures: no vomiting (clonidine 63%; fentanyl 20%); vomiting occurred more frequently with fentanyl (32% vomited more than three times; clonidine none; p=0.001). Fentanyl resulted in more oxygen desaturation (at least two episodes: fentanyl 20%; clonidine 0; p<0.001). Clonidine resulted in lower mean (SD) area under the curve for systolic blood pressure (fentanyl 106.5 [11.0]; clonidine 95.7mmHg [7.9]) and heart rate (fentanyl 104.9 beats per minute [13.6]; clonidine 85.3 [11.5]; p<0.001).Interpretation: Clonidine and fentanyl provide adequate analgesia with low rates of muscle spasm, resulting in low diazepam use. The choice of epidural additive should be based upon the most tolerable side-effect profile. [ABSTRACT FROM AUTHOR]

Purpose: Variable airway function is a central feature of the asthmatic condition. Thus, habitually active asthmatics are certain to exercise under conditions of variable airway (dys)function. The purpose of this study was to determine the effects of variable preexercise airway function on ventilation during whole-body exercise in asthmatic adults. Methods: Eight mild asthmatic (age = 26 yr; V˙O2peak = 49 mL·kg-1·min-1) and nine nonasthmatic (age = 30 yr; V˙O2peak = 46 mL·kg-1·min-1) adults performed constant workrate cycling exercise to exhaustion after four separate interventions: 1) a control trial (CON); 2) inhalation of fast-acting β2-agonist (BD); 3) eucapnic voluntary hyperpnea challenge (BC); and 4) sham to the hyperpnea (SHAM). Pulmonary function was assessed at baseline and after each intervention. Exercise ventilation and operating lung volumes were compared among the four exercise trials in both control and asthmatic subjects. Results: Baseline pulmonary function was significantly lower in asthmatic subjects compared with control subjects. In asthmatic subjects, postintervention (i.e., preexercise) forced expiratory volume 1.0 s was significantly different among the four exercise trials (CON = 3.5 ± 0.4, BD = 4.1 ± 0.4, SHAM = 3.6 ± 0.3, BC = 2.8 ± 0.3 L, P < 0.05), whereas it was not different in control subjects. There were no differences in exercise ventilation or operating lung volumes during exercise among the four trials either within asthmatic subjects or between control and asthmatic subjects. Conclusions: These findings suggest that the state of airway function-whether bronchodilated or bronchoconstricted-before exercise in the mild asthmatic does not affect the exercise ventilatory response. Thus, ventilatory system function in the asthmatic appears to be responsive to the acute requirement for increased airflow during whole-body exercise. [ABSTRACT FROM AUTHOR]

Highlights: [•] Children with CP and PWMI of different gestational age differ in functional profile. [•] Those born ≤34 weeks have more functional limitations than those born >34 weeks. [•] Spasticity is the most prevalent movement disorder for both groups. [•] Future research should investigate severity of PWMI related to gestational age. [Copyright &y& Elsevier]

Background: Preterm infants ≤32 weeks' gestation are increasingly being managed on continuous positive airway pressure (CPAP), without prior intubation and surfactant therapy. Some infants treated in this way ultimately fail on CPAP and require intubation and ventilation. Objectives: To define the incidence, predictors and consequences of CPAP failure in preterm infants managed with CPAP from the outset. Methods: Preterm infants 25-32 weeks' gestation were included in the study if inborn and managed with CPAP as the initial respiratory support, with division into two gestation ranges and grouping according to whether they were successfully managed on CPAP (CPAP-S) or failed on CPAP and required intubation <72 h (CPAP-F). Predictors of CPAP failure were sought, and outcomes compared between the groups. Results: 297 infants received CPAP, of which 65 (22%) failed, with CPAP failure being more likely at lower gestational age. Most infants failing CPAP had moderate or severe respiratory distress syndrome radiologically. In multivariate analysis, CPAP failure was found to be predicted by the highest FiO2 in the first hours of life. CPAP-F infants had a prolonged need for respiratory support and oxygen therapy, and a higher risk of death or bronchopulmonary dysplasia at 25-28 weeks' gestation (CPAP-F 53% vs. CPAP-S 14%, relative risk 3.8, 95% CI 1.6, 9.3) and a substantially higher risk of pneumothorax at 29-32 weeks. Conclusion: CPAP failure in preterm infants usually occurs because of unremitting respiratory distress syndrome, is predicted by an FiO2 ≥0.3 in the first hours of life, and is associated with adverse outcomes. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cardiac allograft vasculopathy (CAV) is a major late complication in cardiac transplant recipients and has a relevant impact on outcome of these patients. Aims of this study: to compare, in cardiac transplant recipients patients, the diagnostic value of pressure/volume relationship (ESPVR) during dobutamine stress echocardiography (DSE) for coronary artery disease, assessed by Multislice Computed Tomography (MSCT), and by coronary angiography (CA). We also analyzed any possible relationship between ESPVR and the Health Related Quality of Life of the patients (HRQoL), evaluated by SF-36 questionnaire. Methods: 25 consecutive patients underwent DSE within 24 hours after MSCT coronary angiogram and then they underwent CA. The HRQoL questionnaire was administered to the patients in the settings of DSE. They were followed-up for 6 months. Results: DSE has a sensitivity in detecting CAV of 67%, specificity of 95%, positive predictive value of 67% and negative predictive value of 95%; DSE with ESPVR has a sensitivity of 100%, specificity of 95%, positive predictive value of 75%, negative predictive value of 100%; MSCT has a sensitivity of 100%; specificity of 82%; positive predictive value of 43%; negative predictive value of 100%. Htx recipients with a flat-biphasic ESPVR, although asymptomatic, perceived a worst HRQoL compared with the up-sloping ESPVR population, and this is statistically significant for the general health (p 0.0004), the vitality (p 0.0013) and the mental health (p 0.021) SF-36 subscale. Conclusions: Evaluation with DSE and ESPVR is accurate in the clinical control of heart transplant recipients reserving invasive evaluation only for patients with abnormal contractility indexes. [ABSTRACT FROM AUTHOR]

The 66-kilodalton isoform of the growth factor adapter Shc (p66Shc) translates oxidative damage into cell death by acting as reactive oxygen species (ROS) producer within mitochondria. However, the signaling link between cellular stress and mitochondrial proapoptotic activity of p66Shc was not known. We demonstrate that protein kinase C β, activated by oxidative conditions in the cell, induces phosphorylation of p66Shc and triggers mitochondrial accumulation of the protein after it is recognized by the prolyl isomerase Pin1. Once imported, p66Shc causes alterations of mitochondrial Ca2+ responses and three-dimensional structure, thus inducing apoptosis. These data identify a signaling route that activates an apoptotic inducer shortening the life span and could be a potential target of pharmacological approaches to inhibit aging. [ABSTRACT FROM AUTHOR]

Background: Very large cohorts that span an entire population raise new prospects for the conduct of multiple trials that speed up advances in prevention or treatment while reducing participant, financial and regulatory burden. However, a review of literature reveals no blueprint to guide this systematically in practice. This Statement of Intent proposes how diverse trials may be integrated within or alongside Generation Victoria (GenV), a whole-of-state Australian birth cohort in planning, and delineates potential processes and opportunities.Methods: Parents of all newborns (estimated 160,000) in the state of Victoria, Australia, will be approached for two full years from 2021. The cohort design comprises four elements: (1) consent soon after birth to follow the child and parent/s until study end or withdrawal; retrospective and prospective (2) linkage to clinical and administrative datasets and (3) banking of universal and clinical biosamples; and (4) GenV-collected biosamples and data. GenV-collected data will focus on overarching outcome and phenotypic measures using low-burden, universal-capable electronic interfaces, with funding-dependent face-to-face assessments tailored to universal settings during the early childhood, school and/or adult years.Results: For population or registry-type trials within GenV, GenV will provide all outcomes data and consent via traditional, waiver, or Trials Within Cohorts models. Trials alongside GenV consent their own participants born within the GenV window; GenV may help identify potential participants via opt-in or opt-out expression of interest. Data sharing enriches trials with outcomes, prior data, and/or access to linked data contingent on custodian's agreements, and supports modeling of causal effects to the population and between-trials comparisons of costs, benefits and utility. Data access will operate under the Findability, Accessibility, Interoperability, and Reusability (FAIR) and Care and Five Safes Principles. We consider governance, ethical and shared trial oversight, and expectations that trials will adhere to the best practice of the day.Conclusions: Children and younger adults can access fewer trials than older adults. Integrating trials into mega-cohorts should improve health and well-being by generating faster, larger-scale evidence on a longer and/or broader horizon than previously possible. GenV will explore the limits and details of this approach over the coming years. [ABSTRACT FROM AUTHOR]

Idiopathic dilatation of the pulmonary artery (IDPA) is an uncommon anomaly occurring in 0.6% of patients with congenital heart disease. IDPA is characterized by the enlargement of the main pulmonary artery with or without dilatation of the right and left pulmonary arteries. We describe 2D and Real-Time 3D Echocardiography findings in a young adult with IDPA. To the best of our knowledge this is the first case reporting all echocardiographic findings diagnostic for IDPA. [ABSTRACT FROM AUTHOR]

Idiopathic dilatation of the pulmonary artery (IDPA) is an uncommon anomaly occurring in 0.6% of patients with congenital heart disease. IDPA is characterized by the enlargement of the main pulmonary artery with or without dilatation of the right and left pulmonary arteries. We describe 2D and Real-Time 3D Echocardiography findings in a young adult with IDPA. To the best of our knowledge this is the first case reporting all echocardiographic findings diagnostic for IDPA. [ABSTRACT FROM AUTHOR]

Congenitally corrected transposition of the great arteries (CCTGA) is a rare disease accounting for 0.5-1.4% of patients with congenital heart disease. In this congenital cardiopathy, the left atrium is connected to the right ventricle, from which the aorta stems. We present a case of an adult with CCTGA associated with aortic stenosis and bicuspid aortic valve-an association not yet described to our knowledge. (Echocardiography 2012;29:E13-E15) [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to describe Doppler-echocardiography values of Carpentier-Edwards Perimount Standard (CEPS) and Carpentier-Edwards Perimount Magna (CEPM) aortic prosthetic valves, evaluated by a single, experienced echo-laboratory, early in the postoperative phase.Methods: Three-hundred-seventy-seven consecutive patients, who had had a CEPS or a CEPM implanted in our Hospital due to aortic stenosis and/or insufficiency, underwent baseline Doppler echocardiography evaluation within 7 days after surgery. Hemodynamic performances of CEPS and CEPM were accurately described, evaluating flow-dependent (transprosthetic velocities and gradients) and flow-independent (effective orifice area, indexed effective orifice area and Doppler velocity index) Doppler-echocardiography parameters.Results: Out of the 377 patients 48.8% were men (n = 184), mean age was 74.63 ± 6.77 years, mean BSA was 1.78 ± 0.18 m2, mean ejection fraction was 57.78 ± 8%. Two-hundred and sixty two CEPS and 115 CEPM were implanted. Comparing size-by-size CEPS with CEPM, both prostheses showed a good hemodynamic profile, with fairly similar values of pressure gradients (PGmax and mean, in mmHg, = 37,18 ± 11.57 and 20.81 ± 7.44 in CEPS n°19 compared to 32,47 ± 7,76 and 17,67 ± 4.63 in CEPM n°19 and progressively lower in higher sized prostheses, having PGmax and mean 15 ± 3,16 and 9.15 ± 1,29 in CEPS n°29 compared to 15,67 ± 1,53 and 9 ± 1 in CEPM n°29) and EOAi (being 0,65 ± 0,33 cm²/m² in CEPS n°19 compared to 0,77 ± 0,29 cm²/m² in CEPM n°19 and progressively higher in higher sized prostheses, being 1,28 ± 0,59 cm²/m² in CEPS n°29 compared to 1,07 ± 0,18 cm²/m² in CEPM n°29), the latter resulting, however, basically less flow obstructive.Conclusions: Our data confirm the good hemodynamic performance of both aortic bioprostheses and the more favourable hemodynamic profile of CEPM compared to CEPS, pointing out the need to perform routinely an accurate baseline Doppler-echocardiography evaluation early after surgery to allow an adequate interpretation of data at follow-up. [ABSTRACT FROM AUTHOR]