Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Mechanical activation of vagal afferents involves opposing cation and TREK1 currents and NO regulation.

Vagal afferents convey signals of mechanical stimulation in the gut to the brain, which is essential for the regulation of food intake. However, ion channels sensing mechanical stimuli are not fully understood. This study aimed to examine the ionic currents activated by mechanical stimulation and a possible neuro-modulatory role of nitric oxide on vagal afferents. Nodose neuronal currents and potentials, and intestinal afferent firing by mechanical stimulation were measured by whole-cell patch clamp, and in vitro afferent recording, respectively. Osmotically activated cation and two-pore domain K+ currents were identified in nodose neurons. The membrane potential displayed a biphasic change under hypotonic stimulation. Cation channel-mediated depolarization was followed by a hyperpolarization mediated by K+ channels. The latter was inhibited by l-methionine (TREK1 channel inhibitor) and l-NNA (nitric oxide synthase inhibitor). Correspondingly, mechanical stimulation activated opposing cation and TREK1 currents. NOS inhibition decreased TREK1 currents and potentiated jejunal afferent nerve firing induced by mechanical stimuli. This study suggested a novel activation mechanism of ion channels underlying adaptation under mechanical distension in vagal afferent neurons. The guts' ability to perceive mechanical stimuli is vital in determining how it responds to food intake. The mechanosensation through ion channels could initiate and control gut function.

Mechanisms of reduced leptin-mediated satiety signaling during obesity.

BACKGROUND/OBJECTIVES: Disrupted leptin signaling in vagal afferent neurons contributes to hyperphagia and obesity. Thus, we tested the hypothesis that intrinsic negative regulators of leptin signaling, suppressor of cytokine signaling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) underlie dysfunctional leptin-mediated vagal afferent satiety signaling during obesity. METHODS: Experiments were performed on standard chow-fed control mice, high-fat fed (HFF), or low-fat fed (LFF) mice. SOCS3 and PTP1B expression were quantified using western blot and quantitative PCR. Nodose ganglion neuronal excitability and jejunal afferent sensitivity were measured by patch clamp and extracellular afferent recordings, respectively. RESULTS: Increased expression of SOCS3 and PTP1B were observed in the jejunum of HFF mice. Prolonged incubation with leptin attenuated nodose ganglion neuronal excitability, and this effect was reversed by inhibition of SOCS3. Leptin potentiated jejunal afferent nerve responses to CCK in LFF mice but decreased them in HFF mice. Inhibition of SOCS3 restored impaired vagal afferent neuronal excitability and afferent nerve responses to satiety mediators during obesity. Two-pore domain K+ channel (K2P) conductance and nitric oxide (NO) production that we previously demonstrated were elevated during obesity were decreased by inhibitions of SOCS3 or PTP1B. CONCLUSIONS: This study suggests that obesity impairs vagal afferent sensitivity via SOCS3 and PTP1B, likely as a consequence of obesity-induced hyperleptinemia. The mechanisms underlying leptin resistance appear also to cause a more global impairment of satiety-related vagal afferent responsiveness.

Cefazolin susceptibility of coagulase-negative staphylococci (CoNS) causing late-onset neonatal bacteraemia.

BACKGROUND: CoNS bacteraemia causes significant neonatal morbidity. Previous work has suggested that ß-lactam antibiotics vary in their binding affinity to PBP2a (produced by the mecA gene) present in most CoNS. OBJECTIVES: We evaluated cefazolin MICs for CoNS isolated in an Australian neonatal ICU (NICU) and correlated them with isolate genotype and phenotype. METHODS: Significant blood isolates from 2009 to 2017 were speciated and underwent broth microdilution testing for cefazolin, cefoxitin, oxacillin and flucloxacillin. Correlation with mecA presence and PBP2a expression was evaluated. A selection of Staphylococcus capitis isolates underwent WGS. RESULTS: The CoNS (n = 99) isolates were confirmed as S. capitis (n = 57), Staphylococcus epidermidis (n = 32), Staphylococcus haemolyticus (n = 2) and Staphylococcus warneri (n = 8). The MIC of cefazolin was ≤2 mg/L for 30% of isolates and 75% had an MIC of ≤8 mg/L (MIC90 = 16 mg/L). This contrasted with MIC90s of cefoxitin, oxacillin and flucloxacillin, which were all ≥32 mg/L. WGS found a number of S. capitis isolates closely related to the globally established NRCS-A clone. CONCLUSIONS: CoNS displayed distinctly lower MIC values of cefazolin than of other agents tested. MIC variation may be related to binding affinity of PBP2a or regulation of expression of mecA by mecR1-mecI functional genes. Further, NRCS-A S. capitis strains were present in this Australian NICU before and after the unit underwent physical relocation, which raised questions about a common environmental source. It is considered justified to conduct a randomized clinical trial that assesses cefazolin versus vancomycin for management of late-onset neonatal sepsis.

Femto-LASIK outcomes obtained by a fellowship trainee during a refractive surgery training program.

PURPOSE: To report, for the first time, the clinical outcomes and patient satisfaction of laser refractive surgery performed by a trainee during a corneal and refractive surgery fellowship program in Latin America. METHODS: This prospective and interventionist study reviewed the clinical charts of the first 100 consecutive refractive surgery cases performed by a single Cornea Fellowship trainee between March 2018 and June 2018 in the Blindness Prevention Association of Mexico (Asociación para Evitar la Ceguera en Mexico). Femtosecond LASIK was performed in all eyes. Visual and refractive outcomes were evaluated during the first year of follow-up. Patient satisfaction was measured using 5 author-created questions 6 months after surgery. RESULTS: Data of 100 eyes of 50 consecutive patients were evaluated. One year after the surgery, mean uncorrected distance visual acuity (UDVA) was 0.01 logMAR. Spherical equivalent error passed from -3.91 ± 2.28 D preoperatively to -0.22 ± 0.28 D. No eyes lost lines in corrected distance visual acuity (CDVA). Manifest refraction maintained stable during the first year after surgery. The five author-created questions revealed a high level of confidence and patient satisfaction. CONCLUSIONS: Femto-LASIK performed by a corneal and refractive surgery fellowship trainee showed good refractive and visual outcomes, as well as high patient satisfaction and confidence in a refractive surgery centre in Latin America.

Real-world clinical profile, treatment patterns and patient-reported outcomes in a subset of HR+/HER2- advanced breast cancer patients with poor prognostic factors: data from an international study.

BACKGROUND: Patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) and disease-related poor prognostic factors are not well characterized. We aimed to describe patient demographics, disease characteristics, treatment patterns and patient-reported outcomes in a subset of HR+/HER2- ABC patients with these factors [at the time when cyclin-dependent kinase (CDK) 4 and 6 inhibitors were being introduced] and understand how these factors informed treatment decisions at the time of the survey. METHODS: Real-world data were derived from a large, multinational, point-in-time survey of oncologists and their consulting patients with HR+/HER2- ABC in the EU5 and USA over March-June 2017, at the start of the changing treatment landscape. Analysis focused on four poor prognostic factors: visceral metastases, liver metastases (subset of visceral metastases), progesterone receptor-negative status and high tumor grade. RESULTS: In total, 2259 patients with HR+/HER2- ABC had records eligible for this analysis. At least one poor prognostic factor was present in 63% of patients (most common visceral metastases; least common progesterone receptor-negative status), with varying degrees of overlap between factors. For physician-reported outcomes, pain increased, whereas performance status and activities of daily living declined with presence of poor prognostic factors, especially liver metastases. No clear trends were observed for patient-reported outcomes. Treatment with combined endocrine therapy plus CDK4 and 6 inhibitors was infrequent, as these agents were entering the market. CONCLUSIONS: More than 60% of the HR+/HER2- ABC Adelphi Real World Disease Specific Programme™ sample had ≥1 disease-related poor prognostic factor, and patients appeared to be heterogeneous regarding occurrence and distribution of these factors. These patients typically have increased pain and reduced performance status, highlighting the importance of implementing effective therapy with CDK4 and 6 inhibitors. Future studies could inform how the treatment landscape has evolved over time with respect to patients with poor prognostic factors.

Resultados de Femto-LASIK obtenidos por un fellow durante un programa de formación en cirugía refractiva / Femto-LASIK outcomes obtained by a fellowship trainee during a refractive surgery training program

Objetivo Informar por primera vez sobre los resultados clínicos y la satisfacción de los pacientes operados de cirugía refractiva con láser por un fellow durante un programa de formación en cirugía corneal y refractiva en Latinoamérica. Métodos En este estudio prospectivo e intervencionista se revisaron las historias clínicas de los primeros 100 casos consecutivos de cirugía refractiva realizados por un solo fellow del departamento de córnea de la Asociación para Evitar la Ceguera en México entre marzo de 2018 y junio de 2018. La técnica LASIK asistida por femtosegundo se realizó en todos los ojos. Los resultados visuales y refractivos se evaluaron durante el primer año de seguimiento. La satisfacción del paciente se midió 6 meses después de la cirugía con 5 preguntas creadas por el autor. Resultados Se evaluaron datos de 100 ojos de 50 pacientes consecutivos. Después de 12 meses de la cirugía, la agudeza visual no corregida (AVNC) fue de 0,01logMAR. El equivalente esférico pasó de –3,91±2,28D preoperatoriamente a –0,22±0,28D. No se perdieron líneas en la agudeza visual mejor corregida (AVMC). La refracción manifiesta se mantuvo estable durante el primer año después de la cirugía. Las 5 preguntas creadas por el autor revelaron un alto grado de confianza y satisfacción del paciente. Conclusiones Los resultados refractivos y visuales obtenidos mediante Femto-LASIK por un fellow de cirugía corneal y refractiva fueron buenos. Del mismo modo se demostró una alta satisfacción y confianza del paciente en el cirujano en periodo de aprendizaje en un centro formativo de cirugía refractiva en Latinoamérica (AU)

Purpose To report, for the first time, the clinical outcomes and patient satisfaction of laser refractive surgery performed by a trainee during a corneal and refractive surgery fellowship program in Latin America. Methods This prospective and interventionist study reviewed the clinical charts of the first 100 consecutive refractive surgery cases performed by a single Cornea Fellowship trainee between March 2018 and June 2018 in the Blindness Prevention Association of Mexico (Asociación para Evitar la Ceguera en Mexico). Femtosecond LASIK was performed in all eyes. Visual and refractive outcomes were evaluated during the first year of follow-up. Patient satisfaction was measured using 5 author-created questions 6 months after surgery. Results Data of 100 eyes of 50 consecutive patients were evaluated. One year after the surgery, mean uncorrected distance visual acuity (UDVA) was 0.01logMAR. Spherical equivalent error passed from –3.91±2.28D preoperatively to –0.22±0.28D. No eyes lost lines in corrected distance visual acuity (CDVA). Manifest refraction maintained stable during the first year after surgery. The five author-created questions revealed a high level of confidence and patient satisfaction. Conclusions Femto-LASIK performed by a corneal and refractive surgery fellowship trainee showed good refractive and visual outcomes, as well as high patient satisfaction and confidence in a refractive surgery centre in Latin America (AU)

Change in EEG Activity is Associated with a Decrease in Tinnitus Awareness after rTMS.

OBJECTIVE: To examine how 1Hz and 10Hz rTMS temporarily influence ratings of tinnitus loudness, annoyance, and awareness. The thalamocortical dysrhythmia (TCD) model of tinnitus was tested by examining changes in spectral power and coherence of resting state EEGs from baseline to each phase of treatment and correlating these data with change in tinnitus. METHODS: Nineteen participants completed a double-blind, placebo (sham rTMS) controlled, within-subjects study with crossover between the two active rTMS treatment conditions. An imposed order effect, sham rTMS first, eliminated drift of active treatment into the placebo condition. The primary outcome measures were analogue ratings of tinnitus loudness, annoyance, and awareness, assessed repeatedly at baseline and during treatment, and 64 channel, resting state EEGs collected at baseline and the end of each treatment phase. Active rTMS consisted of 1800 pulses at 110% of motor threshold over temporal cortex delivered at 1Hz and 10Hz over four days. The research design also examined the effect of rTMS immediately following stimulation, regression to the mean in tinnitus ratings made over multiple days, and differences between treatment responders and non-responders. RESULTS: There was no immediate effect of rTMS on tinnitus during a single rTMS session. Regression to the mean in tinnitus ratings occurred over three days of baseline and four days of treatment (both sham and active rTMS). After accounting for regression to the mean in the statistical model, 1Hz rTMS led to a significant decrease in tinnitus awareness from baseline and 10Hz rTMS trended in the same direction, whereas sham rTMS showed little change from baseline other than regression to the mean. Changes from baseline in spectral power of the resting state EEG provided partial support for predictions based on TCD model of tinnitus for active 1 and 10Hz rTMS but not sham rTMS. However, only an increase in beta coherence correlated significantly with a decrease in tinnitus awareness. Changes in the EEG were robust in treatment responders but absent among non-responders and during sham rTMS. CONCLUSIONS: A positive response to rTMS for tinnitus is associated with an rTMS-induced change in beta coherence of the EEG. Increased beta coherence may be a biomarker of the rTMS effect; a "top-down" modulation of the EEG that promotes habituation to tinnitus. Participants whose tinnitus did not improve after rTMS did not show any changes in the EEG.

N-terminal Domain of TDP43 Enhances Liquid-Liquid Phase Separation of Globular Proteins.

Liquid-liquid phase separation (LLPS) of proteins is involved in a growing number of cellular processes. Most proteins with LLPS harbor intrinsically disordered regions (IDR), which serve as a guideline to search for cellular proteins that potentially phase separate. Herein, we reveal that oligomerization lowers the barriers for LLPS and could act as a general mechanism to enhance LLPS of proteins domains independent of IDR. Using TDP43 as a model system, we found that deleting its IDR resulted in LLPS that was dependent on the oligomerization of the N-terminal domain (NTD). Replacing TDP43's NTD with other oligomerization domains enhanced the LLPS proportionately to the state of oligomerization. In addition to TDP43, fusing NTD to other globular proteins without known LLPS behavior also drove their phase separation in a manner dependent on oligomerization. Finally, we demonstrate that heterooligomers composed of NTD-fused proteins can be driven into droplets through NTD interactions. Our results potentiate a new paradigm for using oligomerization domains as a signature to systematically identify cellular proteins with LLPS behavior, thus broadening the scope of this exciting research field.

Severe Acute Respiratory Syndrome Coronavirus 2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

BACKGROUND: Child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of SARS-CoV-2-related illnesses that the viruses causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (aged <21 years) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time polymerase chain reaction assay. RESULTS: Of 382 children, 293 (77%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (P < .0001), less likely to have asthma (P = .005), and more likely to have an infected sibling contact (P = .001) than uninfected children. Children aged 6-13 years were frequently asymptomatic (39%) and had respiratory symptoms less often than younger children (29% vs 48%; P = .01) or adolescents (29% vs 60%; P < .001). Compared with children aged 6-13 years, adolescents more frequently reported influenza-like (61% vs 39%; P < .001) , and gastrointestinal (27% vs 9%; P = .002), and sensory symptoms (42% vs 9%; P < .0001) and had more prolonged illnesses (median [interquartile range] duration: 7 [4-12] vs 4 [3-8] days; P = 0.01). Despite the age-related variability in symptoms, wWe found no difference in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while asthma is associated with decreased risk. Age-related differences in clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for coronavirus disease 2019 and in developing screening strategies for schools and childcare settings.

SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.

BACKGROUND: Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children. METHODS: We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay. RESULTS: Of 382 children, 289 (76%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have a history of asthma (p=0.009), and more likely to have an infected sibling contact (p=0.0007) than uninfected children. Children ages 6-13 years were frequently asymptomatic (38%) and had respiratory symptoms less often than younger children (30% vs. 49%; p=0.008) or adolescents (30% vs. 59%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p=0.002), gastrointestinal (26% vs. 9%; p=0.003), and sensory symptoms (43% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.004]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. CONCLUSIONS: Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while a history of asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.

Biotin supplementation causes erroneous elevations of results in some commercial serum 25-hydroxyvitamin d (25OHD) assays.

The Vitamin D External Quality Assessment Scheme (DEQAS) distributes serum samples globally, on a quarterly basis, to assess participants' performance of specific methods for 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D). DEQAS occasionally circulates samples containing high levels of substances found in certain clinical situations e.g. 25-OHD2, 24,25-(OH)2D3, hypertriglyceridemia. The increased availability and use of health supplements containing biotin has led to case reports of assay interference in methods utilizing a biotin-streptavidin detection system. In October 2018, DEQAS included a serum sample (545) containing exogenous biotin (concentration =586 µg/L) which was analyzed by a total of 683 laboratories using 35 different methods. The same serum sample (544) without exogenous biotin was also included in the 5-sample set. All methods (760 laboratories) performed satisfactorily on sample 544 giving an All-Laboratory Trimmed Mean = 50.2 ± 6.5 nmol/L (±SD, CV = 12.9 %). The target value for this sample 544 (& 555) was 47.4 nmol/L as determined by Centers for Disease Control and Prevention (CDC) Atlanta, Georgia using their LC-MS/MS reference method. In contrast, #545 containing the exogenous biotin was reported by only 683 laboratories and gave an All-Laboratory Trimmed Mean = 66.8 ± 37.6 nmol/L (±SD, CV = 56.3 %). As expected, LC-MS/MS methods (143 labs) reported similar results for both 544 = 48.9 ± 4.4 nmol/L (±SD) and 545 = 48.3 ± 4.5 nmol/L (±SD) showing that assays involving chromatographic steps are unaffected by the presence of biotin. Several of the antibody-based assays including Abbott Architect, DiaSorin Liaison, Beckman Unicel and Siemens Centaur are also unaffected by the addition of biotin. Two assays, IDS-iSYS and Roche Total 25OHD, both of which use biotin-streptavidin, exhibit biotin interference yielding values with a significant positive bias for 545 of 102.6 nmol/L ± 78.7 nmol/L (±SD) and 517.8 nmol/L ± 209.8 nmol/L (±SD) respectively. Interestingly, the failure to report sample 545 data from 77 laboratories is due solely to those running Roche Total 25OHD or Roche Vitamin D Total II assays. Given the prevalence of the adversely affected assays (25 % of DEQAS users) and the high volume of 25OHD testing, clinicians using these assays should, where possible, only measure 25OHD when patients are off biotin.

Estimating uncertainty of target values for DEQAS serum materials.

The External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) distributes human serum samples to laboratories across the world to assess their performance in measuring serum total 25-hydroxyvitamin D [25(OH)D], i.e. the sum of the concentrations of serum 25(OH)D2 and 25(OH)D3. In 2013 DEQAS, in collaboration with the Vitamin D Standardization Program (VDSP), became an accuracy-based EQAS when the National Institute for Standards and Technology (NIST) began assigning 25(OH)D target values to DEQAS serum samples using their Joint Committee for Traceability in Laboratory Medicine (JCTLM) approved reference measurement procedure (RMP). Historically, NIST has performed 4 determinations of 25-OHD2 and 25-OHD3 on each sample and used the mean values to calculate a single 'target value' for Total 25-OHD against which performance was judged. By definition the target values cannot be exact and each is associated with a level of uncertainty. The total uncertainty (UNIST) has two components, one from the 25(OH)D2, and 25(OH)D3 measurements and the other associated with the calibration procedure. The total combined uncertainty is calculated by adding up these uncertainties. In future, uncertainties will be attached to the target value in each DEQAS serum sample, starting with the next distribution cycle in 2019. Confidence intervals obtained using these uncertainties will allow DEQAS participants to determine if their result agrees with the NIST assigned target value. Furthermore, if the value falls within the confidence interval the laboratory's assay would be regarded as traceable, i.e. standardized, to the NIST RMP.

Predicting Pharmacist Dispensing Practices and Comfort Related to Pre-exposure Prophylaxis for HIV Prevention (PrEP).

To identify factors associated with pharmacist dispensing practice and comfort counseling patients about pre-exposure prophylaxis for HIV prevention (PrEP). Cross-sectional 2016 census of Indiana managing pharmacists measured PrEP awareness, comfort dispensing and counseling patients. Modified Poisson models with robust error variance estimated relative risks and confidence intervals. 15.8% of 284 pharmacists had dispensed PrEP and 11.6% had consulted about it. Dispensing and comfort counseling were associated with confidence in knowledge about PrEP medication adherence and adverse effects of PrEP medication; awareness about PrEP before the survey, number of full time pharmacists in their pharmacy, and increases in new HIV cases from 2015 to 2016 in communities served. Comfort counseling about PrEP was associated with the belief that pharmacists can be an important resource for HIV and HCV treatment.

External Quality Assessment of 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) assays.

The discovery that mutations of the CYP24A1 gene are a cause of idiopathic infantile hypercalcemia (IIH) has revived interest in measuring serum 24,25(OH)2D3. Several studies have also suggested that a high 25-hydroxyvitamin D3(25-OHD3):24,25(OH)2D3 ratio might provide additional diagnostic information in the investigation of vitamin D deficiency. Measurement of 24,25(OH)2D3 is necessarily restricted to laboratories with mass spectrometry methods although cross reactivity of the metabolite in immunoassays for 25-OHD is a potential cause of misleading results. The international External Quality Assessment (EQA) scheme for vitamin D metabolites (DEQAS) was set up in 1989. In 2013 DEQAS became an accuracy based EQA for 25-OHD with 'target values' assigned by the National Institute of Standards and Technology (NIST) Reference Measurement Procedure (RMP). A pilot scheme for serum 24,25(OH)2D3 was started in 2015 and participants were asked to measure the metabolite on each of the 5 samples sent out for 25-OHD. Inter-laboratory agreement was poor but this may reflect methodological differences, in particular different approaches to assay standardization. An important potential contribution to reducing variability among assays was the development by NIST of a 24,25(OH)2D3 RMP and its use in assigning values to SRMs 972a, 2973 and 2971, supported by the NIH Office of Dietary Supplements (ODS) as part of the Vitamin D Standardization Program (VDSP) effort.

Evaluation of the robustness of polarization attraction for 10.7-GBaud NRZ-BPSK after long-haul 100-GHz DWDM transmission.

An investigation was carried out on the polarization attraction (PA) of a polarization-scrambled 10.7-GBaud NRZ-BPSK signal in a 1-km-long highly nonlinear fiber (HNLF). For the back-to-back case, PA on an ASE-loaded signal yielded a receiver sensitivity penalty of ≈ 14.5 dB at the ITU-T G.975.1.I3 FEC threshold of 3.5 × 10-3, relative to matched-filter reception theory. After long-haul 100-GHz DWDM transmission in a recirculating loop, PA on the output signal was found to achieve approximately the same receiver sensitivity performance, as that of the back-to-back case. From these experiments, it is concluded that the Gordon-Mollenauer effect due to propagation in the HNLF during PA dominates other impairments including those arising from the long-haul 100-GHz DWDM recirculating loop transmission.

Scalable Synthesis of Hydrido-Disiloxanes from Silanes: A One-Pot Preparation of 1,3-Diphenyldisiloxane from Phenylsilane.

A simple, one-pot, and high-yielding synthesis of 1,3-diphenyldisiloxane is presented. The preparation of similar symmetrical disiloxane materials is also accomplished with this same protocol. This mechano-chemical procedure is efficient and highly scalable, furnishing a convenient route to hydrido-disiloxanes from widely accessible commercially available silanes.