Influence of the Sea Surface Microlayer on Oceanic Iodine Emissions.

The influence of organic compounds on iodine (I2) emissions from the O3 + I- reaction at the sea surface was investigated in laboratory and modeling studies using artificial solutions, natural subsurface seawater (SSW), and, for the first time, samples of the surface microlayer (SML). Gas-phase I2 was measured directly above the surface of liquid samples using broadband cavity enhanced absorption spectroscopy. I2 emissions were consistently lower for artificial seawater (AS) than buffered potassium iodide (KI) solutions. Natural seawater samples showed the strongest reduction of I2 emissions compared to artificial solutions with equivalent [I-], and the reduction was more pronounced over SML than SSW. Emissions of volatile organic iodine (VOI) were highest from SML samples but remained a negligible fraction (<1%) of the total iodine flux. Therefore, reduced iodine emissions from natural seawater cannot be explained by chemical losses of I2 or hypoiodous acid (HOI), leading to VOI. An interfacial model explains this reduction by increased solubility of the I2 product in the organic-rich interfacial layer of seawater. Our results highlight the importance of using environmentally representative concentrations in studies of the O3 + I- reaction and demonstrate the influence the SML exerts on emissions of iodine and potentially other volatile species.

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

Enhanced wintertime oxidation of VOCs via sustained radical sources in the urban atmosphere.

Daytime atmospheric oxidation chemistry is conventionally considered to be driven primarily by the OH radical, formed via photolytic sources. In this paper we examine how, during winter when photolytic processes are slow, chlorine chemistry can have a significant impact on oxidative processes in the urban boundary layer. Photolysis of nitryl chloride (ClNO2) provides a significant source of chlorine atoms, which enhances the oxidation of volatile organic compounds (VOCs) and the production of atmospheric pollutants. We present a set of observations of ClNO2 and HONO made at urban locations in central England in December 2014 and February 2016. While direct emissions and in-situ chemical formation of HONO continue throughout the day, ClNO2 is only formed at night and is usually completely photolyzed by midday. Our data show that, during winter, ClNO2 often persists through the daylight hours at mixing ratios above 10-20 ppt (on average). In addition, relatively high mixing ratios of daytime HONO (>65 ppt) provide a strong source of OH radicals throughout the day. The combined effects of ClNO2 and HONO result in sustained sources of Cl and OH radicals from sunrise to sunset, which form additional ozone, PAN, oxygenated VOCs, and secondary organic aerosol. We show that radical sources such as ClNO2 and HONO can lead to a surprisingly photoactive urban atmosphere during winter and should therefore be included in atmospheric chemical models.

Marine iodine emissions in a changing world.

Iodine is a critical trace element involved in many diverse and important processes in the Earth system. The importance of iodine for human health has been known for over a century, with low iodine in the diet being linked to goitre, cretinism and neonatal death. Research over the last few decades has shown that iodine has significant impacts on tropospheric photochemistry, ultimately impacting climate by reducing the radiative forcing of ozone (O3) and air quality by reducing extreme O3 concentrations in polluted regions. Iodine is naturally present in the ocean, predominantly as aqueous iodide and iodate. The rapid reaction of sea-surface iodide with O3 is believed to be the largest single source of gaseous iodine to the atmosphere. Due to increased anthropogenic O3, this release of iodine is believed to have increased dramatically over the twentieth century, by as much as a factor of 3. Uncertainties in the marine iodine distribution and global cycle are, however, major constraints in the effective prediction of how the emissions of iodine and its biogeochemical cycle may change in the future or have changed in the past. Here, we present a synthesis of recent results by our team and others which bring a fresh perspective to understanding the global iodine biogeochemical cycle. In particular, we suggest that future climate-induced oceanographic changes could result in a significant change in aqueous iodide concentrations in the surface ocean, with implications for atmospheric air quality and climate.

Antidiabetic effects of 11beta-HSD1 inhibition in a mouse model of combined diabetes, dyslipidaemia and atherosclerosis.

AIM: 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is considered to contribute to the aetiology of the metabolic syndrome, and specific inhibitors have begun to emerge as treatments for insulin resistance and other facets of the syndrome, including atherosclerosis. Given the role of glucocorticoids and 11beta-HSD1 in the anti-inflammatory response and the involvement of inflammation in the development of atherosclerosis, 11beta-HSD1 inhibition may exacerbate atherosclerosis. Our aim was to investigate in vivo the effects of a specific 11beta-HSD1 inhibitor (2922) on atherosclerosis while assessing glucose homeostasis. METHODS: We conducted a 12-week study administering 2922 (at three doses, 3, 10 and 100 mg/kg body weight) in Ldlr 3KO (Ldlr(-/-)Apob(100/100)Lep(ob/ob)) mice, a genetic model of obesity, insulin resistance, dyslipidaemia and atherosclerosis. Rosiglitazone and simvastatin were used to test the responsiveness of our model in both types of therapy. RESULTS: 2922 was effective in reducing 11beta-HSD1 activity in inguinal adipose tissue (>90% for 100 mg/kg) and was efficacious in improving glucose homeostasis at doses > or =10 mg/kg. Plasma insulin, blood glucose, glucose tolerance and homeostatic model assessment indices were all improved in mice treated with 2922 (100 mg/kg) compared with control animals. Despite an improvement in these parameters, no differences were observed in body weight, adipose or lean tissue masses in the 2922-treated mice. Interestingly, circulating lipids, proinflammatory cytokines and atherosclerosis were unaltered in response to 2922, although a small reduction in LDL cholesterol was detected. CONCLUSIONS: Importantly, 11beta-HSD1 inhibition leads to improved glucose metabolism and does not result in a worsening of atherosclerotic lesion area, yet retained antidiabetic potential in the face of multiple severe metabolic aberrations. This study reinforces the potential use of 11beta-HSD1 inhibitors in patients with the metabolic syndrome without negatively impacting atherosclerosis.

Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy.

Missense mutations of the lamin A/C gene, LMNA, have been recently identified in Dunnigan-type familial partial lipodystrophy (FPLD), which belongs to a heterogeneous group of rare disorders affecting adipose tissue distribution and metabolism. In this study, we sequenced the LMNA coding region from patients presenting with FPLD or other forms of lipodystrophy. We identified two heterozygous mutations in exon 8, R482W and R482Q, in FPLD patients (six families and one individual) with various clinical presentations. In addition, we found a novel heterozygous mutation (R584H) in exon 11, encoding specifically the lamin A isoform, in a patient with typical FPLD. Clinical and biochemical investigations in FPLD patients revealed that the expression and the severity of the phenotype were markedly dependent on sex, with female patients being more markedly affected. In subjects with generalized lipoatrophy, either congenital (13 case subjects) or acquired (14 case subjects), or Barraquer-Simon syndrome (2 case subjects), the entire LMNA coding sequence was normal. Although FPLD mutations are predominantly localized in exon 8 of LMNA, the finding of a novel mutation at codon 584, together with the R582H heterozygous substitution recently described, confirms that the C-terminal region specific to the lamin A isoform is a second susceptibility region for mutations in FPLD.

A clinical study of 57 children with fetal anticonvulsant syndromes.

BACKGROUND: Anticonvulsants taken in pregnancy are associated with an increased risk of malformations and developmental delay in the children. To evaluate the pattern of abnormalities associated with prenatal anticonvulsant exposure further, we undertook a clinical study of 57 children with fetal anticonvulsant syndromes. METHODS: Fifty two children were ascertained through the Fetal Anticonvulsant Syndrome Association and five were referred to the Aberdeen Medical Genetics Service. Pregnancy and medical history were obtained through a standardised questionnaire and interview and the children were examined. RESULTS: Thirty four (60%) were exposed in utero to valproate alone, four (7%) to carbamazepine alone, four (7%) to phenytoin alone, and 15 (26%) to more than one anticonvulsant. Forty six (81%) reported behavioural problems, 22 (39%) with hyperactivity or poor concentration of whom four (7%) had a diagnosis of attention deficit and hyperactivity disorder. Thirty four (60%) reported two or more autistic features, of whom four had a diagnosis of autism and two of Asperger's syndrome. Forty four (77%) had learning difficulties, 46 (81%) had speech delay, 34 (60%) had gross motor delay, and 24 (42%) had fine motor delay. Nineteen (33%) had glue ear and 40 (70%) had joint laxity involving all sizes of joints. Of 46 who had formal ophthalmic evaluation, 16 (34%) had myopia. CONCLUSIONS: Speech delay, joint laxity, glue ear, and myopia are common in the fetal anticonvulsant syndromes and autistic features and hyperactivity form part of the behavioural phenotype.

Long term health and neurodevelopment in children exposed to antiepileptic drugs before birth.

OBJECTIVE: To investigate the frequency of neonatal and later childhood morbidity in children exposed to antiepileptic drugs in utero. DESIGN: Retrospective population based study. SETTING: Population of the Grampian region of Scotland. PARTICIPANTS: Mothers taking antiepileptic drugs in pregnancy between 1976 and 2000 were ascertained from hospital obstetric records and 149 (58% of those eligible) took part. They had 293 children whose health and neurodevelopment were assessed. MAIN OUTCOME MEASURES: Frequencies of neonatal withdrawal, congenital malformations, childhood onset medical problems, developmental delay, and behaviour disorders. RESULTS: Neonatal withdrawal was seen in 20% of those exposed to antiepileptic drugs. Congenital malformations occurred in 14% of exposed pregnancies, compared with 5% of non-exposed sibs, and developmental delay in 24% of exposed children, compared with 11% of non-exposed sibs. After excluding cases with a family history of developmental delay, 19% of exposed children and 3% of non-exposed sibs had developmental delay, 31% of exposed children had either major malformations or developmental delay, 52% of exposed children had facial dysmorphism compared with 25% of those not exposed, 31% of exposed children had childhood medical problems (13% of non-exposed sibs), and 20% had behaviour disorders (5% of non-exposed). CONCLUSION: Prenatal antiepileptic drug exposure in the setting of maternal epilepsy is associated with developmental delay and later childhood morbidity in addition to congenital malformation.

Investigation of corneal ablation efficiency using ultraviolet 213-nm solid state laser pulses.

PURPOSE: To determine the threshold and efficiency of corneal ablation for various values of laser fluence at the ultraviolet wave length of 213 nm. METHODS: A commercial Q-switched Nd:YAG laser was used to produce the fifth harmonic wavelength of 213 nm. Ablation trials were carried out on porcine corneas. Slit ablations of dimensions 0.5 x 2.5 mm were performed using seven values of laser fluence to obtain the most efficient fluence for ablation. The morphology of each ablation was obtained using a computer-automated confocal profiling system. These profiles were then analyzed to determine the ablation depth for the range of fluence values used. RESULTS: A fluence in the region of 200 mJ/cm2 was found to be the most efficient for ablation. The efficiency in this region was approximately 0.35 mm3/J, and the ablation rate was found to be 0.6 microm/pulse. The ablation threshold was found to occur at a fluence of 50 mJ/cm2. In the region of highest efficiency, the peak varied slightly in the fluence range between 150 and 250 mJ/cm2. CONCLUSIONS: This study confirms that the corneal ablation properties at 213 nm are comparable with those at the 193-nm excimer laser wavelength. Increased pulse energy was obtained for the fifth harmonic of Nd:YAG lasers at 213 nm through the use of new nonlinear optical crystals to perform the frequency conversion. A solid state laser is feasible to replace the excimer gas laser for performing refractive surgery procedures. For the first time, the increased energy at 213 nm allows large-beam ablations to be performed at this wavelength.

Evidence for an immune complex vasculitis in neonatal necrotising enterocolitis.

Despite many attractive hypotheses, neonatal necrotising enterocolitis (NNEC) remains a disease of unknown aetiology. By means of the immunofluorescent direct sandwich technique we have demonstrated immune complex deposition in the small vessels of the diseased bowel wall. We believe this is the first report of evidence of an immunological reaction occurring in this disease.

A study of protein turnover in preterm neonates using 15N enrichment of urinary ammonia.

Hydrolysed yeast protein labelled with 15N was used to measure protein turnover, protein synthesis and protein breakdown in preterm infants. The yeast tracer was given as a bolus intragastric dose and protein turnover was determined from the 15N enrichment of urinary ammonia over known periods of about 12 h. Six boys (birthweight less than 1500 g) with gestation of 27-35 weeks were studied either two or three times at post-natal ages ranging from 13 to 54 d. There was no significant correlation between protein turnover with increasing post-conceptional or post-natal age. There was considerable interindividual variation and reproducibility varied between different infants. We suggest that this is a convenient non-invasive technique for monitoring serially nitrogen and protein metabolism in infants and that as such it merits further assessment.

Follow up care of bereaved parents after treatment withdrawal from newborns.

OBJECTIVE: To explore parents' experiences of bereavement care after withdrawal of newborn intensive care. DESIGN: Face to face interviews with 108 parents of 62 babies born over two calendar years in the East of Scotland. RESULTS: Only 22% were seen by six weeks after the death, 10% were not recalled before 6-11 months, and 8% were not seen at all in the first year. All except one couple saw the neonatologist who had cared for their baby. Only 33% remembered a neonatal nurse being present. Most (88%) were seen in the study hospital. Parents highlighted a number of specific needs. Appointments should be: (a) scheduled soon after the death of the baby and certainly within two months of the death irrespective of whether or not autopsy results are available; (b) with the named neonatologist; (c) in a setting away from the hospital if possible. Parents value: (a) efforts to find out how they are coping; (b) full frank information given sensitively to enable them to build up a cohesive picture of what happened and assess their future risks; (c) reassurance where possible, but half truths, false reassurances, and broken promises are unacceptable. CONCLUSIONS: Follow up care is a crucial part of the management of families from whose babies treatment has been withdrawn. Resources devoted to it should be re-examined to provide a service more in tune with parental need. In choosing the place, timing, and conduct of the meeting, staff should be sensitive to the expressed wishes of the parents themselves.

Consent to autopsy for neonates.

OBJECTIVES: To determine parents' views on autopsy after treatment withdrawal. DESIGN: Face to face interviews with 59 sets of bereaved parents (108 individual parents) for whose 62 babies there had been discussion of treatment withdrawal. RESULTS: All except one couple were asked for permission for postmortem examination; 38% refused. The main reasons for declining were concerns about disfigurement, a wish to have the child left in peace, and a feeling that an autopsy was unnecessary because the parents had no unanswered questions. The diagnosis, the age of the child, and the approach of the consultant appeared to influence consent rates. Of those who agreed to autopsies, 92% were given the results by the neonatologist concerned. Whether or not they had agreed to the procedure, at 13 months no parent expressed regrets about their decision. CONCLUSIONS: Autopsy rates in the East of Scotland stand at 62%. Parents' perceptions are an important element in consent to postmortem examination.

Fetal fat measurement by magnetic resonance imaging.

A method to assess the average percentage of fetal fat with respect to other fetal tissue is described. This method was then used to assess the percentage of fat in 13 normal fetuses who had a magnetic resonance imaging (MRI) examination late in pregnancy (38-41 weeks). The scans of a further 13 fetuses of diabetic mothers and one case of intrauterine growth retardation (IUGR), all of whom had MRI examinations in the last 3 years, were reviewed and similar calculations were carried out. Whilst the percentage fat range in the normal group was large, it was still possible to discern a difference between the normal, diabetic and IUGR cases.

Suboptimal care and perinatal mortality in ten European regions: methodology and evaluation of an international audit.

BACKGROUND: A European concerted action (the EuroNatal study) investigated differences in perinatal mortality between countries of Europe. This report describes the methods used in the EuroNatal international audit and discusses the validity of the results. METHODS: Perinatal deaths between 1993 and 1998 in regions of ten European countries were identified. The categories of death chosen for the study were singleton fetal deaths at 28 or more weeks of gestational age, all intrapartum deaths at 28 or more weeks of gestational age and neonatal deaths at 34 or more weeks of gestational age. Deaths with major congenital anomalies were excluded. An international audit panel used explicit criteria to review all cases, which were blinded for region. Subjective interpretation was used in cases of events or interventions where explicit criteria did not exist. Suboptimal factors were identified in the antenatal, intrapartum and neonatal periods, and classified as 'maternal/social', due to 'infrastructure/service organization', or due to 'professional care delivery'. The contribution of each suboptimal factor to the fatal outcome was listed and consensus was reached on a final grade using a procedure that included correspondence and plenary meetings. RESULTS: In all regions combined, 90% of all known or estimated cases in the selected categories were included in the audit. In total, 1619 cases of perinatal death were audited. Consensus was reached in 1543 (95%) cases. In 75% of all cases, the grade was based on explicit criteria. In the remaining cases, consensus was reached within subpanels without reference to predefined criteria. There was reasonable to good agreement between and within subpanels, and within panel members. CONCLUSIONS: The international audit procedure proved feasible and led to consistent results. The results that relate to suboptimal care will need to be studied in depth in order to reach conclusions about their implications for assessing the quality of perinatal care in the individual regions.

Surgical treatment of necrotizing enterocolitis: a population-based study in the Grampian region, Scotland.

Ninety-two cases of necrotizing enterocolitis (NEC) were diagnosed in the Grampian Region of Scotland between 1978 and 1984, for a regional incidence of 2.2/1,000 live births. Twenty-seven cases (29.3%) required surgery, 19 acutely and eight for delayed stricture. Acute operative mortality was 10.5%. Disease-related mortality was 3.3%, and overall mortality was 8.7%. Follow-up ranged from 15 to 77 months for surgical patients, with only three of 23 survivors having increased bowel frequency.

Neonatal upper limb ischaemia. The case for conservative management.

General supportive measures, the ability to avoid infection, the natural tendency to improvement and the feasibility of major reconstructive procedures later suggest that neonatal limb ischaemia should be managed conservatively at first, despite an alarming appearance. The number of infants at risk, especially due to prematurity and effective resuscitation, is theoretically increasing.

Neonatal examination and screening trial (NEST): a randomised, controlled, switchback trial of alternative policies for low risk infants.

OBJECTIVE: To evaluate the effectiveness of one rather than two hospital neonatal examinations in detection of abnormalities. DESIGN: Randomised controlled switchback trial. SETTING: Postnatal wards in a teaching hospital in north east Scotland. PARTICIPANTS: All infants delivered at the hospital between March 1993 and February 1995. INTERVENTION: A policy of one neonatal screening examination compared with a policy of two. MAIN OUTCOME MEASURES: Congenital conditions diagnosed in hospital; results of community health assessments at 8 weeks and 8 months; outpatient referrals; inpatient admissions; use of general practioner services; focused analysis of outcomes for suspected hip and heart abnormalities. RESULTS: 4835 babies were allocated to receive one screening examination (one screen policy) and 4877 to receive two (two screen policy). More congenital conditions were suspected at discharge among babies examined twice (9.9 v 8.3 diagnoses per 100 babies; 95% confidence interval for difference 0.3 to 2.7). There was no overall significant difference between the groups in use of community, outpatient, or inpatient resources or in health care received. Although more babies who were examined twice attended orthopaedic outpatient clinics (340 (7%) v 289 (6%)), particularly for suspected congenital dislocation of the hip (176 (3.6/100 babies) v 137 (2.8/100 babies); difference -0.8; -1.5 to 0.1), there was no significant difference in the number of babies who required active management (12 (0.2%) v 15 (0.3%)). CONCLUSIONS: Despite more suspected abnormalities, there was no evidence of net health gain from a policy of two hospital neonatal examinations. Adoption of a single examination policy would save resources both during the postnatal hospital stay and through fewer outpatient consultations.

Argininosuccinic aciduria--an underdiagnosed cause of neonatal death?

We describe a case of neonatal argininosuccinic aciduria, a condition we suggest is underdiagnosed. Although the clinical presentation can be of overwhelming septicaemia, certain routine biochemical investigations are indicative of this inborn error of urea cycle metabolism.

Keloids.

Keloids are a benign proliferative growth of dermal collagen usually resulting from an excessive tissue response to skin trauma in predisposed individuals. Herein is a review of the history, epidemiology, clinical evaluation, histopathology, immunological theories of progression, and treatment of keloids.