Re-evaluating the structure of consciousness through the symintentry hypothesis.

The Projective Consciousness Model and its extension to the phenomenal selfhood model are the generic invariant structures of consciousness through five symmetries. They include the following: situated 3D spatiality; temporal integration through encompassing the three "nows" that constitute the Now; multimodal synchronic integration; relational phenomenal intentionality; and consciousness entails a pre-reflective awareness of the uniqueness of the phenomenal self. These symmetries stem from the evolution and emergence of the phenomenal self through modeling, and that is realized through the phenomenal modeling of the intentionality relationship. We propose that this set of symmetries is based on and can be explicated in terms of a more fundamental symmetry, symmetry-based modeling. The proposal stems from (a) Kant's transcendental structuralism, which asserts that "Objects" conform to models prescribed through the inherent structure of the phenomenal mind, and (b) Cassirer's proposition that a mathematical group underpins this structure. To validate our proposal, we stipulate this group defining symmetry-based modeling and its emergence and adaptation into structuring the Now. We find that Cassirer's group requires a more powerful dual quaternion operator to be able to support intentionality and the five symmetries. We propose that the efficacy of this operator stems from unifying symmetry-based modeling and intentionality as "symintentry." Symintentry, we argue, is not just a new form of symmetry but is the archetypical form of symmetry. Symintentry provides fresh insights into the nature of symmetry, intentionality, and consciousness.

Management of the Airway in Apert Syndrome.

The management of the airway in Apert syndrome is complex and multidisciplinary. This rare syndrome, occurring in up to approximately 1 in 65,000 live births, results in airway compromise at various anatomic levels, in addition to abnormal central respiratory drive. Obstructive apneas arise because of decreased airway caliber, which may occur in the form of congenital bony nasal stenosis, choanal atresia, a deviated nasal septum, a narrowed nasopharynx, a thick long soft palate, lateral palatal swellings, and a tracheal cartilage sleeve. Central apneas in Apert syndrome arise because of raised intracranial pressure and/or Chiari malformations. The purpose of this study was to investigate our treatment methods and outcomes in optimizing the airway in this complex, rare and interesting cohort of patients who present with airway compromise. Patients with Apert syndrome were retrospectively evaluated during a period from 1990 to 2013. Treatments for obstructive apnea were dilatation of nasal airways and choanal atresia repair, adenoidectomy, tonsillectomy, early midface advancement, and noninvasive ventilation. The insertion of ventriculoperitoneal shunts, fronto-orbital advancement, and Chiari decompression aid in managing central apneas. The authors present our experience at Alder Hey Children's Hospital, Liverpool, one of the 4 Supraregional Craniofacial Units in the United Kingdom.

Observational infant exploratory [(14)C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis.

AIMS: The aims of the study were to compare [(14)C]-paracetamol ([(14)C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group. METHODS: [(14)C]-PARA concentrations in 10-15 µl plasma samples were measured after enteral or i.v. administration of a single [(14)C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. RESULTS: Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h(-1), 1.76 (1.07) l h(-1), 2.93 (2.08) l h(-1) and 2.72 (3.10) l h(-1), t(1/2) values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l(-1) h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). CONCLUSIONS: All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg(-1)) and a microdose (ng kg(-1)) in babies between 35 to 127 weeks post-menstrual age. [(14)C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies.

A novel presentation of inappropriate antidiuretic hormone secretion in Leigh syndrome with the myoclonic epilepsy and ragged red fibers, mitochondrial DNA 8344A>G mutation.

A 17-month-old infant presented with a 2-week history of lethargy, anorexia, and an abnormal respiratory pattern on a previous 4-month history of hypotonia and gross motor delay, suggesting a clinical phenotype of Leigh syndrome. The patient experienced no epileptic seizures. Biochemical investigations were normal other than showing evidence of inappropriate secretion of antidiuretic hormone, and cerebral magnetic resonance imaging (MRI) showed symmetrical lesions in the cervical cord and lower brain stem. Initial screening investigations for a mitochondrial cytopathy were negative. Muscle histochemistry demonstrated reduced staining of cytochrome c oxidase but no ragged red fibers. Blood and muscle-derived DNA demonstrated a high level (92% and 82%, respectively) of the m.8344A>G mutation seen in patients with the mitochondrial cytopathy, ''myoclonic epilepsy with ragged red fibers on muscle biopsy.'' This infant's early presentation including inappropriate antidiuretic secretion due to presumed renal salt loss and rapid course appears to be unique to this mutation.

Novel use of skin substitute as rescue therapy in complicated giant exomphalos.

Giant exomphalos can be successfully managed using conservative or surgical techniques. However, if treatment is complicated by sepsis, early skin cover of the defect becomes necessary. Options include split skin grafting, but in the presence of ongoing infection the risk of graft failure is high and limited skin is available for regrafting. We describe the novel use of a skin substitute (Integra Artificial Skin, Integra Life Sciences Corporation, Plainsboro, NJ) as an alternative to primary grafting in the management of infected giant exomphalos.

Genitourinary malformations as a feature of the Pallister-Hall syndrome.

Pallister-Hall and McKusick-Kaufman syndromes are developmental disorders with well defined phenotypes, distinct loci and different patterns of inheritance. The clinical features can overlap and may cause diagnostic difficulty, particularly if complex genitourinary malformations are present. A case is presented with features of both syndromes but in which a GLI3 mutation has been identified. A literature review of similar cases is presented and it is proposed that these cases probably represent the Pallister-Hall syndrome. A detailed abdominal and perineal examination should be considered in all female patients with the Pallister-Hall syndrome, looking for associated genitourinary anomalies. Conversely, all girls with features suggestive of McKusick-Kaufman syndrome require neuroimaging to look for features of the Pallister-Hall syndrome. The correct diagnosis is important so that the patient and the family may receive appropriate management. It also allows provision for an accurate recurrence risk.

Differences in resting energy expenditure between male and female children with cystic fibrosis.

OBJECTIVES: To evaluate which factors might contribute to raised resting energy expenditure (REE) in patients with cystic fibrosis (CF). STUDY DESIGN: REE and anthropometry were measured in 134 (males = 68) children with CF and 100 (males = 51) controls (range, 3-18.7 years) in an outpatient setting. Bacterial colonization, liver disease, inhaled steroid use, pancreatic and pulmonary function, sex, and genotype were determined and regression analysis was used to determine the predictors of REE in the group with CF. RESULTS: REE for children with CF was increased on average by 7.2% compared with controls. This increase was greater for females than for males. REE in males was positively associated with fat-free mass (FFM), pancreatic insufficiency (PI), and liver disease, and negatively associated with pulmonary function, whereas in females, REE was positively associated with FFM and PI. REE (adjusted for FFM) was higher in children with a severe mutation (5495 +/- 47 kJ) compared with a mild mutation (5,176 +/- 124 kJ, P <.02). CONCLUSIONS: PI, severe mutations, and female sex are the main contributing factors to elevated REE in patients with CF with near normal pulmonary function.

Assessment of adrenal function in the initial phase of meningococcal disease.

OBJECTIVE: To determine the status of the hypothalamic-pituitary-adrenal axis in children who had meningococcal disease and were admitted to 2 regional pediatric intensive care units. METHODS: Sixty-five children (34 boys; median age: 2.5 years; range: 0.2-15 years) had cortisol and adrenocorticotropic hormone (ACTH) levels measured on admission, then at 8 AM and 8 PM during the next 48 hours. At 48 hours, a low-dose short Synacthen test (LDST) (500 ng of 1-24 corticotropin/m2) was performed in 42 patients (19 boys). Normal ranges for 8 AM cortisol and ACTH levels in unstressed children were 140 to 500 nmol/L and 2 to 11.3 pmol/L, respectively. Adrenal insufficiency (AI) was defined as a peak cortisol <500 nmol/L on the LDST or an 8 AM cortisol value <140 nmol/L. RESULTS: Five (7.7%) of the 65 children died, including 1 with primary AI. Cortisol levels were elevated on admission (median: 1122 mmol/L; range: 65-2110 nmol/L) with 81% of values more than the 8 AM normal range. The median ACTH level on admission was within the 8 AM normal range, but 40% of values were more than the 8 AM normal range. However, 7% and 8% of cortisol and ACTH values, respectively, were less than the normal range. Both cortisol and ACTH levels fell thereafter and showed no diurnal variation during the 48-hour profile. Six (14%) of the 42 failed the LDST. These patients had significantly lower mean 8 AM cortisol values than those with a normal peak value on the LDST. Five additional patients who did not have the LDST had 8 AM cortisol values <140 nmol/L. In the diagnosis of AI, the sensitivity of the 8 AM mean cortisol value at a cutoff of 400 nmol/L, judged against the LDST, was 83%; the specificity was 81%. CONCLUSIONS: During the initial phase of meningococcal disease, raised cortisol and ACTH levels indicate an appropriate stress response within the hypothalamic-pituitary-adrenal axis. However, a substantial subpopulation (11 [16.9%] of 65) has evidence of adrenal dysfunction during this period. Morning cortisol values in the initial phase of meningococcal disease could be used as a potential early index of AI.

Differing pathways of lower airway colonization and infection according to mode of ventilation (endotracheal vs tracheotomy).

OBJECTIVES: To determine whether the pathogenesis of lower airway colonization and infection was endogenous (via the oropharynx) or exogenous (via the endotracheal tube or tracheotomy) during the 2 modes of ventilation in the same subset of children requiring long-term ventilation. DESIGN: Prospective, observational cohort study. SETTING: A pediatric intensive care unit and a respiratory ward. PATIENTS: Consecutive admissions between September 1, 1993, and August 30, 1998. MEASUREMENTS AND MAIN RESULTS: Cultures were obtained simultaneously from the oropharynx and tracheobronchial tree on admission to the pediatric intensive care unit, at placement of the tracheotomy, and afterward twice weekly. Forty-five patients were studied. Lower airways were always sterile in 6 children, 39 children (87%) developed a total of 82 episodes of colonization, and 17 (38%) progressed to 25 episodes of infection. The number of infected children was halved once they had a tracheotomy (7 children [16%]). Of the 107 episodes of colonization and infection, 41 and 66 occurred during endotracheal ventilation and via a tracheotomy, respectively. Primary endogenous episodes of colonization and infection due to bacteria present in the admission flora in the pediatric intensive care unit were significantly more common with endotracheal ventilation than during ventilation via a tracheotomy (31/41 [76%] vs 36/66 [55%]; P =.03). Secondary endogenous and exogenous episodes of colonization and infection due to bacteria associated with the respiratory ward were significantly more frequent when ventilation was continued through a tracheotomy than during endotracheal ventilation (30/66 [45%] vs 10/41 [24%]; P =.02). CONCLUSIONS: Surveillance samples allow the distinction between primary endogenous ("imported" bacteria) from secondary endogenous and exogenous ("nosocomial" microorganisms) colonization and infection. This classification permits the development of preventive strategies to control both endogenous and exogenous pathways.