Pedi-R-MAPP: The development of a nutritional awareness tool for use in remote paediatric consultations using a modified Delphi consensus.

BACKGROUND & AIMS: The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation. METHODS: A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool. RESULTS: The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations. Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised. CONCLUSION: The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.

Resonant Doppler effect in systems with variable delay.

We demonstrate that a time-varying delay in nonlinear systems leads to a rich variety of dynamical behaviour, which cannot be observed in systems with constant delay. We show that the effect of the delay variation is similar to the Doppler effect with self-feedback. We distinguish between the non-resonant and the resonant Doppler effect corresponding to the dichotomy between conservative delays and dissipative delays. The non-resonant Doppler effect leads to a quasi-periodic frequency modulation of the signal, but the qualitative properties of the solution are the same as for constant delays. By contrast, the resonant Doppler effect leads to fundamentally different solutions characterized by low- and high-frequency phases with a clear separation between them. This is equivalent to time-multiplexed dynamics and can be used to design systems with well-defined multistable solutions or temporal switching between different chaotic and periodic dynamics. We systematically study chaotic dynamics in systems with large dissipative delay, which we call generalized laminar chaos. We derive a criterion for the occurrence of different orders of generalized laminar chaos, where the order is related to the dimension of the chaotic attractor. The recently found laminar chaos with constant plateaus in the low-frequency phases is the zeroth-order case with a very low dimension compared to the known high dimension of turbulent chaos in systems with conservative delay. This article is part of the theme issue 'Nonlinear dynamics of delay systems'.

Delayed and fractional use of enzymatic debridement with nexobrid for extensive burn injury: a case report.

Selective enzymatic debridement is increasingly being used in cases of burn wounds. However, until now the use of Nexobrid has been limited to 15% of total body surface area (TBSA) and immediate use on admission day. A 61-year-old Caucasian male suffered a severe burn injury that affected 95% TBSA. After surgical escharotomy and tracheotomy on admission day, we successfully performed a fractional enzymatic debridement of 54% of the TBSA in three different sessions within four days. This case report reveals that a delayed and fractional application of Nexobrid to more than 15% TBSA is possible.

Le débridement enzymatique sélectif des brûlures est de plus en plus utilisé. Cependant, cette technique était jusqu'ici limitée à 15% de la surface corporelle totale (SCT). Nous rapportons le cas d'un homme de 61 ans brûlé sur 95% SCT. Après une trachéotomie et des incisions de décharge le jour de son entrée, nous avons réalisé un débridement enzymatique sur 54% SCT sur 4 j en 3 séances. Cette observation montre que l'utilisation séquentielle de Nexobrid® permet de traiter plus de 15% SCT.

Faculty professional development in emergent pedagogies for instructional innovation in dental education.

Innovative pedagogies have significantly impacted health professions' education, dental education included. In this context, faculty, defined in this study as instructor in higher education, has been increasingly required to hone their instructional skills. The purpose of this exploratory study was to share the design, implementation and preliminary outcomes of two programmes to enhance dental faculty's instructional skills, the Teaching and Learning Seminar Series and the Course Director Orientation. Data sources included faculty and student surveys developed and administered by the researchers; data extracted from the learning management system; reports from the learning analytics tool; and classroom observations. Participants' satisfaction, self-reported learning, instructional behavioural change, and impact on student learning behaviours and institutional practice were assessed borrowing from Kirkpatrick's 4-level model of evaluation of professional development effectiveness. Initial findings showed that faculty in both programmes reported positive learning experiences. Participants reported that the programmes motivated them to improve instructional practice and improved their knowledge of instructional innovation. Some faculty reported implementation of new instructional strategies and tools, which helped create an active and interactive learning environment that was welcomed by their students. The study contributes to literature and best practice in health sciences faculty development in pedagogy and may guide other dental schools in designing professional development programmes.

Guidelines for the prevention, detection and therapy of vitamin d deficiency in adults

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{µ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{µ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{µ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.

Molecular characterization of cat factor XII gene and identification of a mutation causing factor XII deficiency in a domestic shorthair cat colony.

Coagulation factor XII (FXII) may be important in cardiovascular and inflammatory diseases. We have identified and characterized a naturally occurring mutation in the feline FXII gene that results in a mutant protein and enzymatic loss of activity. Feline intron/exon gene structure and sequence were acquired by comparing DNA sequences obtained from a fragmented Felis catus genomic sequence and the National Center for Biotechnology Information's Cross Species Megablast of multiple species' FXII gene sequences. Fourteen exons ranging in size from 57 to 222 base pairs were confirmed spanning 8 Kb on chromosome A1. The 1828-base pair feline FXII messenger RNA (mRNA) sequence contains an open reading frame that encodes a protein of 609 amino acids with high homology to human FXII protein. Total RNA and mRNA purified from liver tissue of 4 wild-type/normal and 8 FXII-deficient cats confirmed the predicted mRNA sequence and identified one important single-nucleotide polymorphism (SNP). A single base deletion in exon 11 of the FXII coding gene in our colony of cats results in deficient FXII activity. Translation of the mRNA transcript shows a frame shift at L441 (C441fsX119) resulting in a nonsense mutation and a premature stop codon with a predicted 560-amino acid protein. The mutant FXII protein is truncated in the 3' proteolytic light chain region of the C-terminus, explaining its loss of enzymatic activity. This study is the first molecular characterization of the feline FXII gene and the first identification of an FXII mutation in the domestic cat, providing insights into the origin and nature of feline FXII deficiency.

mGlu2/3 agonist-induced hyperthermia: an in vivo assay for detection of mGlu2/3 receptor antagonism and its relation to antidepressant-like efficacy in mice.

An assay to detect the on-target effects of mGlu2/3 receptor antagonists in vivo would be valuable in guiding dosing regimens for the exploration of biological effects of potential therapeutic import. Multiple approaches involving blockade of mGlu2/3 receptor agoinist-driven behavioral effects in mice and rats were investigated. Most of these methods failed to provide a useful method of detection of antagonists in vivo (e.g., locomotor activity). In contrast, the mGlu2/3 receptor agonist LY379268 produced dose-dependent increases in body temperature of mice. The hyperthermic effects of LY379268 was abolished in mGlu2 and in mGlu2/3 receptor null mice but not in mGlu3 null mice. Hyperthermia was not produced by an mGlu8 receptor agonist. Agonist-induced hyperthermia was prevented in a dose-dependent manner by structurally-distinct mGlu2/3 receptor antagonists. The blockade was stereo-specific. Moreover, this biological readout was responsive to both orthosteric and to negative allosteric modulators of mGlu2/3 receptors. Antagonism of agonist-induced hyperthermia predicted antidepressant-like efficacy in the mouse forced swim test. As with the hyperthermic response, the antidepressant-like effects of mGlu2/3 receptor antagonists were shown to be due to mGlu2 and not to mGlu3 or mGlu8 receptors through the use of receptor knock-out mice. The ability to rapidly assess on-target activity of mGlu2/3 receptor antagonists enables determination of parameters for setting efficacy doses in vivo. In turn, efficacy-related data in the preclinical laboratory can help to set expectations of therapeutic potential and dosing in humans.

Pharmaceutical principles of acid inhibitors: unmet needs.

Despite the well-established benefits of currently approved delayed-release proton pump inhibitors (PPIs) in the treatment of acid-related diseases, the unmet needs are still present and although often frustrating, they challenge clinicians. The unmet needs relate to the lack of complete control of acid secretion with oral PPI administration in the management of patients with gastroesophageal symptoms. These substantial groups of patients, who do not respond completely to standard doses of PPIs, are nonresponders, and their lack of response should be considered as PPI failure. Several mechanisms could explain PPI failure: differences in pharmacokinetics, PPI formulation, dosing time and diet, noncompliance, transient lower esophageal sphincter relaxations, esophageal hypersensitivity, and nocturnal acid breakthrough. To increase the quality of life of these patients and avoid multiple medical consultations and unnecessary investigations, we have to go one step forward and use combined therapy or look towards new treatments beyond acid suppression.

Neuromodulation in a minipig MPTP model of Parkinson disease.

Large animal neuroscience enables the use of conventional clinical brain imagers and the direct use and testing of surgical procedures and equipment from the human clinic. The greater complexity of the large animal brain additionally enables a more direct translation to human brain function in health and disease. Economical, ethical, scientific and practical issues may on the other hand hamper large animal neuroscience. Large animal neuroscience should therefore either be performed in order to examine large animal species dependent problems or to complement promising small animal basic studies by constituting an intermediate research system, bridging small animal CNS research to the human CNS. We have, accordingly, during the last ten years used the Gottingen minipig to examine neuromodulatory treatment modalities such as stem cell transplantation and deep brain stimulation directed towards Parkinson disease. This has been accomplished by the development of a MPTP-based large animal model of Parkinson disease in the Gottingen minipig and the development of stereotaxic and surgical approaches needed to manipulate the Gottingen minipig CNS. The instituted changes in the CNS can be evaluated in the live animal by brain imaging (PET and MR), cystometry, gait analysis, neurological evaluation and by post mortem examination based on histology and stereological analysis.

Avoidant personality disorder and social phobia: distinct enough to be separate disorders?

OBJECTIVE: Existing evidence from anxiety disorder research indicates that social phobics (SP) with avoidant personality disorder (AVPD) experience more anxiety and show more impairment than patients with SP alone. The purpose of this study was to examine whether in patients diagnosed with AVPD, the co-occurrence of SP adds to its severity. We hypothesized that the addition of SP will not add to the severity of AVPD alone. METHOD: Two groups of patients (AVPD=224; AVPD/SP=101) were compared at baseline and 2 years later on multiple demographic and clinical variables. RESULTS: Patients with AVPD and an additional diagnosis of SP differed little from patients with AVPD alone. CONCLUSION: These findings suggest that AVPD and SP may be alternative conceptualizations of the same disorder.

Stressful life events as predictors of functioning: findings from the collaborative longitudinal personality disorders study.

OBJECTIVE: Although much attention has been given to the effects of adverse childhood experiences on the development of personality disorders (PDs), we know far less about how recent life events influence the ongoing course of functioning. We examined the extent to which PD subjects differ in rates of life events and the extent to which life events impact psychosocial functioning. METHOD: A total of 633 subjects were drawn from the Collaborative Longitudinal Personality Disorders Study (CLPS), a multi-site study of four personality disorders--schizotypal (STPD), borderline (BPD), avoidant (AVPD), obsessive-compulsive (OCPD)--and a comparison group of major depressive disorders (MDD) without PD. RESULTS: Borderline personality disorder subjects reported significantly more total negative life events than other PDs or subjects with MDD. Negative events, especially interpersonal events, predicted decreased psychosocial functioning over time. CONCLUSION: Our findings indicate higher rates of negative events in subjects with more severe PDs and suggest that negative life events adversely impact multiple areas of psychosocial functioning.

PET evaluation of the uptake of N-[11C]methyl CP-643,051, an NK1 receptor antagonist, in the living porcine brain.

Antagonists of neurokinin receptors such as CP-643,051 are presently under investigation as potential antidepressants, but little is known about the brain uptake and distribution of these agents. We developed a method for the efficient N-[11C]methylation of CP-122,721, yielding the NK1 antagonist N-[11C]methyl CP-643,051. The brain uptake and distribution of N-[11C]methyl CP-643,051 were studied by positron emission tomography (PET) in the anaesthetized pig, first in a baseline condition, and again after displacement of specific binding with the NK1 receptor antagonist L-732,138 (0.6 mg/kg, i.v.). In order to validate this displacement procedure, we tested the effects of L-732,138 on cerebral blood flow (CBF) in one pig. We found that N-[11C]methyl CP-643,051 had a distribution volume close to 3 ml g(-1), and a binding potential (pB) of 0.3 in the pig striatum; this binding was displaceable by the L-732,138 pre-treatment, which evoked a small (10-20%) global increase in CBF. We conclude that of N-[11C]methyl CP-643,051 may serve as a lead structure for the development of PET NK-1 ligands of higher specific binding in vivo.

Longitudinal diagnostic efficiency of DSM-IV criteria for obsessive-compulsive personality disorder: a 2-year prospective study.

OBJECTIVE: To examine the longitudinal diagnostic efficiency of the DSM-IV criteria for obsessive-compulsive personality disorder (OCPD). METHOD: At baseline, criteria and diagnoses were determined using diagnostic interviews, and blinded assessments were performed 24 months later with 550 participants. Diagnostic efficiency indices (conditional probabilities, total predictive power, and kappa) were calculated for each criterion determined at baseline, using the independent OCPD diagnosis at follow-up as the standard. RESULTS: Longitudinal diagnostic efficiencies for the OCPD criteria varied; findings suggested the overall predictive utility of 'preoccupied with details', 'rigid and stubborn', and 'reluctant to delegate'. CONCLUSION: These findings suggest the predictive validity of three cognitive-interpersonal OCPD criteria.

Do we really know vitamin and mineral requirements for infants and children?

Infants and young children require vitamins and minerals not only to replace losses through metabolic turnover, but also to increase body reserves as they grow. For infants up to six months of age it is generally assumed that breast milk provides adequate intakes, and average breast milk composition provides the basis of reference intakes for this age group, and the basis for infant formula. It is questionable to what extent the micronutrient content of breast milk reflects the infant's requirements as opposed to the mother's nutritional status. For obvious ethical reasons there have been very few (if any) experiments to determine the micronutrient requirements of infants and children, although studies of intakes in areas where deficiency is common provide an estimate of minimum requirements in some cases. Different national and international authorities have approached the problem of estimating reference intakes for infants and young children in four main ways: linear interpolation between adequate intakes estimated from breast milk composition and the experimentally-determined requirements of young adults; extrapolation forwards from breast milk composition and backwards from the requirements of young adults on the basis of metabolic body weight (body weight0.75), corrected by growth factors; extrapolation backwards from the requirements of young adults on the basis of the energy density of the diet; and by factorial calculation. Despite this, there is considerable concordance between the figures published by different authorities as a result of rounding off to avoid spurious precision.

Distribution of corticotectal cells in macaque.

We compared the cortical inputs to the superficial and deep compartments of the superior colliculus, asking if the corticotectal system, like the colliculus itself, consists of two functional divisions: visual and visuomotor. We made injections of retrograde tracer extending into both superficial and deep layers in three colliculi: the injection site involved mainly the upper quadrant representation in one case, the lower quadrant representation in a second case, and both quadrants in a third. In a fourth colliculus, the tracer injection was restricted to the lower quadrant representation of the superficial layers. After injections involving both superficial and deep layers, labeled cells were seen over V1, many prestriate visual areas, and in prefrontal and posterior parietal cortex. Both the density of labeled cells and the degree of visuotopic order as inferred from the distribution of labeled cells in cortex varied among areas. In visual areas comprising the lower levels of the cortical hierarchy, visuotopy was preserved, whereas in "higher" areas the distribution of labeled cells did not strongly reflect the visuotopic location of the injection. Despite the widespread distribution of labeled cells, there were several areas with few or no labeled cells: MSTd, 7a, VIP, MIP, and TE. In the case with an injection restricted to superficial layers, labeled cells were seen only in V1 and in striate-recipient areas V2, V3, and MT. The results are consistent with the idea that the corticotectal system consists of two largely nonoverlapping components: a visual component consisting of striate cortex and striate-recipient areas, which projects only to the superficial layers, and a visuomotor component consisting of many other prestriate visual areas as well as frontal and parietal visuomotor areas, which projects to the deep compartment of the colliculus.

PET evaluation of a tetracyclic, atypical antidepressant, [N-methyl-11C]mianserin, in the living porcine brain.

We synthesized [N-methyl-11C]mianserin by alkylation of N-desmethyl mianserin with [11C]methyl iodide followed by HPLC purification. We used PET for determining the regional cerebral pharmacokinetics of the radiotracer in anesthetized swine. [N-methyl-11C]Mianserin entered most brain regions readily (range of K1 values: 0.66-1.13), reaching highest levels in the basal ganglia and thalamus. The binding potential of [N-methyl-11C]mianserin was relatively low (range: 0.07-0.50), but regional differences were nonetheless observed, with highest values in the temporal cortex and lowest values in the brainstem. These PET findings, which are the first ones for a tetracyclic, antidepressant drug, show that [N-methyl-11C]mianserin has only a limited degree of regional specificity of binding in the living brain.