[Clear resection margins to avoid escalation of adjuvant therapy in oropharyngeal squamous cell carcinoma]. / Sichere R0-Resektion zur Vermeidung der adjuvanten Therapieeskalation beim Oropharynxkarzinom.

BACKGROUND: Resection margins in patients with oropharyngeal squamous cell carcinoma (OPSCC) are a predictive marker for overall survival (OS) and recurrence-free interval (RFI). Adjuvant therapy is influenced by TNM status, extracapsular extension (ECE), and resection margin status (R) of the primary tumor. The R status can be directly influenced by the head and neck surgeon. The aim of the current study was to evaluate the impact of R status on treatment decisions, RFI, and OS. MATERIALS AND METHODS: All patients with OPSCC who underwent surgery (with/without adjuvant therapy) between 2001 and 2011 were enrolled. Clinical data, survival parameters, histologic data such as ECE, resection margin status, and tumor size were retrospectively collected and analyzed. RESULTS: A total of 208 patients were enrolled. Survival parameters showed that patients with microscopically clear (R0) resection margins had an RFI/OS of 89/87 months. These values decreased in patients with R1 (65/65 months), R2 (38/33 months), and Rx (unclear) resections (59/45 months; p =  0.036/p = 0.001). In patients with ECE and R1 resection, but also in those with R0 resections achieved by follow-up resection and those with Rx resections, adjuvant therapy was escalated. CONCLUSION: Unclear resection status reduces OS and RFI in patients with OPSCC. Therefore, in surgical therapy, clear resection status in the first pass should be strived for to avoid escalation of adjuvant therapy due to an unclear R status.

Correction to: Estimation of exposure durations for vitamin D production and sunburn risk in Switzerland.

In the original article, the authorship list was given as "A. Religi1, C. Backes2,3, A. Chatelan2, J.-L. Bulliard2, L. Vuilleumier4, L. Moccozet1, M. Bochud2, D. Vernez3". This has been updated to "A. Religi*1, C. Backes*2,3, A. Chatelan2, J.-L. Bulliard2, L. Vuilleumier4, L. Moccozet1, M. Bochud 2, D. Vernez3".

Estimation of exposure durations for vitamin D production and sunburn risk in Switzerland.

Although overexposure to solar ultraviolet radiation (UVR) is responsible for cutaneous melanoma and epithelial skin cancer and can cause negative health effects such as sunburn, a "little and often" exposure regime is often suggested to produce naturally recommended vitamin D levels, being essential for skeletal health. This study aimed to quantify solar UV doses needed to trigger 1000 International Units (IU) vitamin D doses and, at the same time, producing sunburn in Switzerland. Solar UV erythema irradiance (in mW/m2) measured at four meteorological stations in Switzerland for the period 2005-2017 were used to evaluate effective solar UV radiation producing 1000 IU vitamin D doses in skin phototype II and III individuals. Daily solar UV exposure durations (in minutes) needed to produce vitamin D with limited sunburn risk were estimated while considering mean vitamin D food intake of the Swiss population and seasonal skin coverage. In summer and spring, with 22% of uncovered skin, 1000 IU vitamin D doses are synthesized in 10-15 min of sun exposure for adults. Exposure durations between erythema risk and 1000 IU vitamin D production vary between 9 and 46 min. In winter and autumn, the recommended vitamin D production without sunburn risks often unachievable, since up to 6.5 h of sun exposure might be necessary considering 8-10% of uncovered skin surface. The vitamin D food intake only represented 10% of the recommended vitamin D production and remained unchanged throughout the year. These findings might clarify why vitamin D deficiency is common in Switzerland. Moreover, exposure durations between recommended vitamin D and increased sunburn risk might only differ by few minutes. Without additional oral vitamin D supplementation, daily doses of vitamin D (1000 IU) are not reachable in autumn and winter months in Switzerland.

Sun exposure to the eyes: predicted UV protection effectiveness of various sunglasses.

The aim of this study was to assess solar ultraviolet radiation (UVR) doses received by the eyes in different exposure situations, and to predict the sun protection effectiveness provided by various styles of sunglasses at facial, periorbital, and ocular skin zones including the cornea and accounting for different head positions. A 3D numeric model was optimized to predict direct, diffuse and reflected erythemally weighted UVR doses received at various skin zones. Precisely defined facial, periorbital, and ocular skin zones, sunglasses (goggles, medium-, and large-sized sunglasses) and three head positions were modeled to simulate daily (08:00-17:00) and midday (12:00-14:00) UVR doses. The shading from sunglasses' frame and lenses' UVR transmission were used to calculate a predictive protection factor (PPF [%]). Highest ocular daily UVR doses were estimated at the uncovered cornea (1718.4 J/m2). Least sun protection was provided by middle-sized sunglasses with highest midday dose at the white lateral (290.8 J/m2) and lateral periorbital zones (390.9 J/m2). Goggles reached almost 100% protection at all skin zones. Large-sized sunglasses were highly effective in winter; however, their effectiveness depended on diffuse UVR doses received. In "looking-up" head positions highest midday UVR doses were received at the unprotected cornea (908.1 J/m2), totally protected when large-sized sunglasses are used. All tested sunglass lenses fully blocked UVR. Sunglasses' protection effectiveness is strongly influenced by geometry, wearing position, head positions, and exposure conditions. Sunglasses do not totally block UVR and should be combined with additional protection means. 3D modeling allows estimating UVR exposure of highly sensitive small skin zones, chronically exposed and rarely assessed.

Long-lived photoluminescence polarization of localized excitons in liquid exfoliated monolayer enriched WS2.

Monolayer transition metal dichalcogenides (TMDs) constitute a family of materials, in which coupled spin-valley physics can be explored and which could find applications in novel optoelectronic devices. However, before applications can be designed, a scalable method of monolayer extraction is required. Liquid phase exfoliation is a technique providing large quantities of the monolayer material, but the spin-valley properties of thus obtained TMDs are unknown. In this work, we employ steady-state and time-resolved photoluminescence (PL) to investigate the relaxation dynamics of localized excitons (LXs) in liquid exfoliated WS2. The results reveal that the circular polarization lifetime of the PL exceeds by at least an order of magnitude the PL lifetime. A rate equations model allows us to reproduce quantitatively the experimental data and to conclude that the observed large and long-lived PL polarization originates from efficient trapping of free excitons at localization sites hindering the intervalley relaxation. Furthermore, our results show that the depolarization process is inefficient for LXs. We discuss various mechanisms leading to this effect such as suppression of intervalley scattering of the LXs or inefficient spin relaxation of the holes.

Biological recognition of graphene nanoflakes.

The systematic study of nanoparticle-biological interactions requires particles to be reproducibly dispersed in relevant fluids along with further development in the identification of biologically relevant structural details at the materials-biology interface. Here, we develop a biocompatible long-term colloidally stable water dispersion of few-layered graphene nanoflakes in the biological exposure medium in which it will be studied. We also report the study of the orientation and functionality of key proteins of interest in the biolayer (corona) that are believed to mediate most of the early biological interactions. The evidence accumulated shows that graphene nanoflakes are rich in effective apolipoprotein A-I presentation, and we are able to map specific functional epitopes located in the C-terminal portion that are known to mediate the binding of high-density lipoprotein to binding sites in receptors that are abundant in the liver. This could suggest a way of connecting the materials' properties to the biological outcomes.

Differences in mortality characteristics in neonates with Down's syndrome.

OBJECTIVE: Neonates with Down's syndrome (nDS) may have multiple medical issues that place them at increased risk for mortality during the newborn period. Goal of this study was to determine if there are differences in baseline characteristics, medical complications or procedures performed during hospitalization between nDS who survived versus those who died during initial hospitalization. STUDY DESIGN: Data from 2000 to 2014 were reviewed using the Pediatric Health Information Systems (PHIS) database on all DS patients admitted to the hospital <30 days postnatal life. Baseline demographics, medical complications, procedures performed and mortality were recorded. Patients were divided into nDS patients who were discharged alive (nDS-a) versus nDS patients who died (nDS-d). Multivariate logistic analysis with odds ratios was performed to determine significant predictors of death. A P<0.05 was considered significant. RESULTS: A total of 5737 nDS were evaluated. Overall mortality was 7.5% (431/5737). nDS-d were more likely than nDS-a to have a lower birth weight (1.0 (0.9 to 1.0)), presence of a diaphragmatic hernia (6.9 (1.9 to 25.1), or a cardiac diagnosis of a pulmonary venous abnormality (6.8 (1.9 to 24.4)), Ebstein's anomaly (3.2 (1.2 to 8.5)) or left-sided obstructive lesion (2.0 (1.3 to 3.0). nDS-d were more likely to develop hydrops (5.7 (3.5 to 9.5)) and necrotizing enterocolitis (1.7 (1.2 to 2.6)). In addition, nDS-d had significantly higher odds of requiring mechanical ventilation (20.7 (9.9 to 43.1)) or extracorporeal membrane oxygenation (8.7 (4.7 to 16.1)). CONCLUSIONS: A number of characteristics, specifically certain cardiac diagnosis, place nDS at increased risk for mortality. Furthermore, development of specific medical complications or need for particular procedures increases the odds for mortality in nDS. Caregivers should be cognizant that they are taking care of a high-risk population nDS with an increased risk for mortality if these variables are present.

Right ventricular performance using myocardial deformation imaging in infants with bronchopulmonary dysplasia.

OBJECTIVE: Right ventricular (RV) performance among infants with bronchopulmonary dysplasia (BPD) remains poorly understood. We tested the hypothesis that myocardial deformation imaging (MDI) strain and strain rate would allow for differentiation between infants with severe and milder forms of BPD, independent of tissue Doppler imaging (TDI) and superior to conventional echocardiographic measurements. STUDY DESIGN: Infants with various severities of BPD (11 with none or mild, 13 with moderate and 10 with severe) underwent conventional echocardiography, TDI and MDI assessments at >36 weeks of corrected gestational age. BPD severity grading was determined according to the National Institutes of Child Health and Disease workshop rating scale by physicians blinded to the echocardiogram results. Group data were compared with one-way analysis of variance or Kruskal-Wallis tests, with post hoc multiple comparisons. RESULTS: No differences in traditional echocardiographic parameters or TDI among the three BPD severity groups were observed; none of the infants had evidence of pulmonary hypertension. Using MDI, infants with severe BPD had lower peak global systolic strain than did infants with moderate BPD (P<0.01) or mild/none BPD (P<0.01). Early and late diastolic strain rate measurements were similar across the three groups. CONCLUSIONS: Among infants with severe forms of BPD, evidence of abnormal RV systolic function was detected with MDI, but not traditional echocardiographic or TDI measurements. Infants with severe forms of BPD may represent a particularly high-risk subgroup for decreased RV performance warranting cardiac surveillance. MDI should be considered as a method to quantitate RV function in this population.

Preparedness of pediatric residents for fellowship: a survey of US neonatal-perinatal fellowship program directors.

OBJECTIVE: To evaluate the preparedness of pediatric residents entering accredited neonatal-perinatal medicine (NPM) fellowships in the United States. STUDY DESIGN: A multi-domain, validated survey was distributed to Program Directors (PDs) of US NPM fellowship programs. The 47-item survey explored 5 domains: professionalism, independent practice, psychomotor ability, clinical evaluation, and academia. A systematic, qualitative analysis on free-text comments was also performed. RESULTS: Sixty-one PDs completed the survey, for a response rate of 62% (61/98). For entering fellows, PDs assessed performance in professionalism positively, including 76% as communicating effectively with parents and 90% treating residents/house-staff with respect. In contrast, most PDs rated performance in psychomotor abilities negatively, including 59% and 79% as deficient in bag-and-mask ventilation and neonatal endotracheal intubation, respectively. Although 62% of PDs assessed entering fellows positively for genuine interest in academic projects, fewer than 10% responded positively that entering fellows understood research protocol design, basic statistics, or were capable of writing a cohesive manuscript well. Thematic clustering of qualitative data revealed deficits in psychomotor ability and academia/scholarship. CONCLUSIONS: On the basis of the perspective of front line educators, graduating pediatric residents are underprepared for subspecialty fellowship training in NPM. To provide the best preparation for pediatric graduates who pursue advanced training, changes to residency education to address deficiencies in these important competencies are warranted.

Revealing the nature of excitons in liquid exfoliated monolayer tungsten disulphide.

Transition metal dichalcogenides (TMD) hold promise for applications in novel optoelectronic devices. There is therefore a need for materials that can be obtained in large quantities and with well understood optical properties. In this report, we present thorough photoluminescence (PL) investigations of monolayer tungsten disulphide obtained via liquid phase exfoliation. As shown by microscopy studies, the exfoliated nanosheets have dimensions of tens of nanometers and thickness of 2.5 monolayers on average. The monolayer content is about 20%. Our studies show that at low temperature the PL is dominated by excitons localized on nanosheet edges. As a consequence, the PL is strongly sensitive to the environment and exhibits an enhanced splitting in magnetic field. As the temperature is increased, the excitons are thermally excited out of the defect states and the dominant transition is that of the negatively charged exciton. Furthermore, upon excitation with a circularly polarized light, the PL retains a degree of polarization reaching 50% and inherited from the valley polarized photoexcited excitons. The studies of PL dynamics reveal that the PL lifetime is on the order of 10 ps, which is probably limited by non-radiative processes. Our results underline the potential of liquid exfoliated TMD monolayers in large scale optoelectronic devices.

Long-chain amine-templated synthesis of gallium sulfide and gallium selenide nanotubes.

We describe the soft chemistry synthesis of amine-templated gallium chalcogenide nanotubes through the reaction of gallium(iii) acetylacetonate and the chalcogen (sulfur, selenium) using a mixture of long-chain amines (hexadecylamine and dodecylamine) as a solvent. Beyond their role as solvent, the amines also act as a template, directing the growth of discrete units with a one-dimensional multilayer tubular nanostructure. These new materials, which broaden the family of amine-stabilized gallium chalcogenides, can be tentatively classified as direct large band gap semiconductors. Their preliminary performance as active material for electrodes in lithium ion batteries has also been tested, demonstrating great potential in energy storage field even without optimization.

Timing of umbilical cord clamping among infants born at 22 through 27 weeks' gestation.

OBJECTIVE: To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation. STUDY DESIGN: This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s). RESULTS: Forty mother-infant pairs were randomized. Infants in the ICC and DCC groups had mean gestational ages (GA) of 24.6 and 24.4 weeks, respectively. No differences were observed between the groups across all available safety measures, although infants in the DCC group had higher admission temperatures than infants in the ICC group (97.4 vs. 96.2 °F, P=0.04). During the first 24 h of life, blood pressures were lower in the ICC group than in the DCC group (P<0.05), despite a threefold greater incidence of treatment for hypotension (45% vs. 12%, P<0.01). Infants in the ICC group had increased numbers of red blood transfusions (in first 28 days of life) than infants in DCC group (4.1±3.9 vs. 2.8±2.2, P=0.04). CONCLUSION: Among infants born at an average GA of 24 weeks', DCC appears safe, logistically feasible, and offers hematological and circulatory advantages compared with ICC. A more comprehensive appraisal of this practice is needed.

Genome-wide copy number profiling of mouse neural stem cells during differentiation.

There is growing evidence that gene amplifications were present in neural stem and progenitor cells during differentiation. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of mouse neural stem cells using TGF-ß and FCS for differentiation induction. Array data were deposited in GEO (Gene Expression Omnibus, NCBI) under accession number GSE35523. Here, we describe in detail the cell culture features and our TaqMan qPCR-experiments to validate the array-CGH analysis. Interpretation of array-CGH experiments regarding gene amplifications in mouse and further detailed analysis of amplified chromosome regions associated with these experiments were published by Fischer and colleagues in Oncotarget (Fischer et al., 2015). We provide additional information on deleted chromosome regions during differentiation and give an impressive overview on copy number changes during differentiation induction at a time line.

Early versus delayed umbilical cord clamping in infants with congenital heart disease: a pilot, randomized, controlled trial.

OBJECTIVE: Delayed umbilical cord clamping (DCC) at birth may provide a better neonatal health status than early umbilical cord clamping (ECC). However, the safety and feasibility of DCC in infants with congenital heart disease (CHD) have not been tested. This was a pilot, randomized, controlled trial to establish the safety and feasibility of DCC in neonates with CHD. STUDY DESIGN: Pregnant women admitted >37 weeks gestational age with prenatal diagnosis of critical CHD were enrolled and randomized to ECC or DCC. For ECC, the umbilical cord was clamped <10 s after birth; for DCC, the cord was clamped ~120 s after delivery. RESULTS: Thirty infants were randomized at birth. No differences between the DCC and ECC groups were observed in gestational age at birth or time of surgery. No differences were observed across all safety measures, although a trend for higher peak serum bilirubin levels (9.2±2.2 vs 7.3±3.2 mg dl(-1), P=0.08) in the DCC group than in the ECC group was noted. Although similar at later time points, hematocrits were higher in the DCC than in the ECC infants during the first 72 h of life. The proportion of infants not receiving blood transfusions throughout hospitalization was higher in the DCC than in the ECC infants (43 vs 7%, log-rank test P=0.02). CONCLUSION: DCC in infants with critical CHD appears both safe and feasible, with fewer infants exposed to red blood cell transfusions than with ECC. A more comprehensive appraisal of this practice is warranted.

Placental transfusion strategies in extremely preterm infants: the next piece of the puzzle.

Evidence is growing on the potential value of enhancing placental-fetal transfusion at birth, with recent endorsement of the practice by the World Health Organization and American College of Gynecologists. However, these recommendations provide clinicians with little guidance on the optimal practice among infants born extremely premature (<28 weeks gestation) and those requiring immediate resuscitation. The goals of this review are to: 1) provide rationale for better outcomes among extremely preterm infants following delayed cord clamping or umbilical cord "milking" than with immediate cord clamping; 2) describe clinical situations that warrant immediate cord clamping following delivery and explore the controversy regarding optimal cord clamping practice among extremely premature infants, including those requiring immediate resuscitation; 3) discuss the quality of evidence in this subgroup of infants; 4) consider areas for future research, with a focus on characterizing if placental-fetal transfusion affects the magnitude or timing of variables associated with physiological transition. The review provided herein suggests that delayed cord clamping or umbilical cord milking can be applied safely to infants born prior to 28 weeks gestation, but the lack of evidence on the best practice among infants born severely depressed and requiring immediate resuscitation, who comprise a greater proportion of infant deliveries at the lowest gestational ages, is recognized. Future studies using well-defined physiologic outcome measures are needed to understand the role of placental transfusion in premature infants' adaptations to extrauterine life.

Arginase I gene single-nucleotide polymorphism is associated with decreased risk of pulmonary hypertension in bronchopulmonary dysplasia.

AIM: To test the hypothesis that there are single-nucleotide polymorphisms (SNPs) in genes of the l-arginine/nitric oxide pathway associated with pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD). METHODS: Neonates with BPD were enrolled (n = 140) and clinical characteristics compared between case (BPD + PH) and control (BPD) groups. DNA was isolated from blood leucocytes and assayed for 17 SNPs in l-arginine/nitric oxide pathway genes by Sequenom massarray. Genes included carbamoyl-phosphate synthetase, ornithine transcarbamylase, argininosuccinate synthase, nitric oxide synthase and arginase. SNPs were selected from the National Center for Biotechnology Information database for their putative functionality. Calculated minor allele frequencies (MAF) of cases and controls were compared using χ2 and logistic regression. RESULTS: Of the 140 patients with BPD, 26% had echocardiographic evidence of PH. Ventilation days were longer for cases than controls (mean 31 vs. 15 days, p < 0.05). Of the 17 SNPs, rs2781666 in arginase I gene was less common in cases (MAF = 0.23) than controls (MAF = 0.37, p = 0.04). The odds of PH decreased by 43% (p = 0.047) for each copy of the SNP minor allele in arginase I gene in patients with BPD. CONCLUSION: Arginase I SNP (rs2781666) may be associated with protection against pulmonary hypertension in preterm neonates with BPD.

Genome-wide copy number profiling to detect gene amplifications in neural progenitor cells.

DNA sequence amplification occurs at defined stages during normal development in amphibians and flies and seems to be restricted in humans to drug-resistant and tumor cells only. We used array-CGH to discover copy number changes including gene amplifications and deletions during differentiation of human neural progenitor cells. Here, we describe cell culture features, DNA extraction, and comparative genomic hybridization (CGH) analysis tailored towards the identification of genomic copy number changes. Further detailed analysis of amplified chromosome regions associated with this experiment, was published by Fischer and colleagues in PLOS One in 2012 (Fischer et al., 2012). We provide detailed information on deleted chromosome regions during differentiation and give an overview on copy number changes during differentiation induction for two representative chromosome regions.

Neonatal abstinence syndrome: transitioning methadone-treated infants from an inpatient to an outpatient setting.

OBJECTIVE: Each year in the US ∼50 000 neonates receive inpatient pharmacotherapy for the treatment of neonatal abstinence syndrome (NAS). The objective of this study is to compare the safety and efficacy of a traditional inpatient only approach with a combined inpatient and outpatient methadone treatment program. STUDY DESIGN: Retrospective review (2007 to 2009). Infants were born to mothers maintained on methadone in an antenatal substance abuse program. All infants received methadone for NAS treatment as inpatient. Methadone weaning for the traditional group (75 patients) was inpatient, whereas the combined group (46 patients) was outpatient. RESULT: Infants in the traditional and combined groups were similar in demographics, obstetrical risk factors, birth weight, gestational age (GA) and the incidence of prematurity (34 and 31%). Hospital stay was shorter in the combined than in the traditional group (13 vs 25 days; P<0.01). Although the duration of treatment was longer for infants in the combined group (37 vs 21 days, P<0.01), the cumulative methadone dose was similar (3.6 vs 3.1 mg kg(-1), P=0.42). Follow-up information (at least 3 months) was available for 80% of infants in the traditional and 100% of infants in the combined group. All infants in the combined group were seen ≤72 h from hospital discharge. Breastfeeding was more common among infants in the combined group (24 vs 8% P<0.05). Following discharge there were no differences between the two groups in hospital readmissions for NAS. Prematurity (34 to 36 weeks GA) was the only predictor for hospital readmission for NAS in both groups (P=0.02, OR 5). Average hospital cost for each infant in the combined group was $13 817 less than in the traditional group. CONCLUSION: A combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and substantially reduces cost. Additional studies are needed to evaluate the potential long-term benefits of the combined approach on infants and their families.

Proposed method of well-child care in a resident's clinic.

Uniformity in a teaching hospital's pediatric outpatient clinic is often inconsistent because of the varying numbers of housestaff involved in patient evaluation. We have developed a flow sheet that defines the appropriate standards of care to be delivered at the Doctors Hospital Pediatric Outpatient Clinic. This flow sheet encompasses a method of rapid assessment of growth, development, physical examination, immunization status, screening laboratory testing, and parental education. We have defined these parameters as the minimal evaluation to be completed at each preschool well-child visit.