A randomized clinical trial to evaluate the efficacy of L-carnitine L-tartrate to modulate the effects of SARS-CoV-2 infection.

Introduction: L-carnitine (LC) has been associated with inflammatory mediator reduction and with downregulating the angiotensin-converting enzyme-2 (ACE2) receptor, which is the target of SARS-CoV-2 attachment. Methods: This pilot phase 2 randomized, double-blind placebo-controlled trial contained two cohorts. Cohort 1 comprised 101 individuals with negative RT-PCR SARS-CoV-2 test results who cohabitated with an individual diagnosed with SARS-CoV-2 infection. Cohort 2 comprised 122 individuals with positive SARS-CoV-2 RT-PCR test results who were asymptomatic or had mild COVID-19 pneumonia symptoms. Participants in each cohort were randomized 1:1 to receive either 2 g elemental oral LC supplementation or placebo daily for 21 days. Primary endpoints included adverse events, SARS-CoV-2 infection incidence in Cohort 1, and disease progressions in Cohort 2. Secondary endpoints included between-group laboratory profile comparisons and Cohort 2 ACE1/ACE2 plasma levels. Disease progression was compared between the Cohort 2 groups using chest computed tomography. Results: In Cohort 1, two SARS-CoV-2 infections occurred in each group. The common adverse events included headache, dyspnea, and tiredness. In Cohort 2, platelet counts were elevated, and fibrinogen levels reduced in the LC group compared with those of the placebo group. Conclusion: Our study showed that LC was well-tolerated and suggests it modulates coagulation pathways. Furthermore, chest computed tomography images of the Cohort 2 LC group showed significant lung lesion improvement, suggesting that LC may slow COVID-19 progression.

The Effect of Capsule-in-Capsule Combinations on In Vivo Disintegration in Human Volunteers: A Combined Imaging and Salivary Tracer Study.

Controlling the time point and site of the release of active ingredients within the gastrointestinal tract after administration of oral delivery systems is still a challenge. In this study, the effect of the combination of small capsules (size 3) and large capsules (size 00) on the disintegration site and time was investigated using magnetic resonance imaging (MRI) in combination with a salivary tracer technique. As capsule shells, Vcaps® HPMC capsules, Vcaps® Plus HPMC capsules, gelatin and DRcaps® designed release capsules were used. The three HPMC-based capsules (Vcaps®, Vcaps® Plus and DRcaps® capsules) were tested as single capsules; furthermore, seven DUOCAP® capsule-in-capsule combinations were tested in a 10-way crossover open-label study in six healthy volunteers. The capsules contained iron oxide and hibiscus tea powder as tracers for visualization in MRI, and two different caffeine species (natural caffeine and 13C3) to follow caffeine release and absorption as measured by salivary levels. Results showed that the timing and location of disintegration in the gastrointestinal tract can be measured and differed when using different combinations of capsule shells. Increased variability among the six subjects was observed in most of the capsule combinations. The lowest variability in gastrointestinal localization of disintegration was observed for the DUOCAP® capsule-in-capsule configuration using a DRcaps® designed release capsule within a DRcaps® designed release outer capsule. In this combination, the inner DRcaps® designed release capsule always opened reliably after reaching the ileum. Thus, this combination enables targeted delivery to the distal small intestine. Among the single capsules tested, Vcaps® Plus HPMC capsules showed the fastest and most consistent disintegration.

The Ander's organ: a mechanism for anti-predator ultrasound in a relict orthopteran.

The use of acoustics in predator evasion is a widely reported phenomenon amongst invertebrate taxa, but the study of ultrasonic anti-predator acoustics is often limited to the prey of bats. Here, we describe the acoustic function and morphology of a unique stridulatory structure - the Ander's organ - in the relict orthopteran Cyphoderris monstrosa (Ensifera, Hagloidea). This species is one of just eight remaining members of the family Prophalangopsidae, a group with a fossil record of over 90 extinct species widespread during the Jurassic period. We reveal that the sound produced by this organ has the characteristics of a broadband ultrasonic anti-predator defence, with a peak frequency of 58±15.5 kHz and a bandwidth of 50 kHz (at 10 dB below peak). Evidence from sexual dimorphism, knowledge on hearing capabilities and assessment of local predators, suggests that the signal likely targets ground-dwelling predators. Additionally, we reveal a previously undescribed series of cavities underneath the organ that probably function as a mechanism for ultrasound amplification. Morphological structures homologous in both appearance and anatomical location to the Ander's organ are observed to varying degrees in 4 of the 7 other extant members of this family, with the remaining 3 yet to be assessed. Therefore, we suggest that such structures may either be more widely present in this ancient family than previously assumed, or have evolved to serve a key function in the long-term survival of these few species, allowing them to outlive their extinct counterparts.

The identity of the Bahama endemic field cricket Gryllus bryanti Morse (Orthoptera: Gryllidae; Gryllinae; Gryllini).

The Bahama endemic field cricket, Gryllus bryanti Morse, 1905, previously known from only the lost female holotype, is redescribed, including designation of a neotype. Known only from Andros and Eleuthera Islands in The Bahamas, where it occurs with G. assimilis, it can be separated from the latter by song, tegmen file characteristics, head wider than pronotum, and genetics.

Accurate and reproducible enumeration of T-, B-, and NK lymphocytes using the BD FACSLyric 10-color system: A multisite clinical evaluation.

Clinical flow cytometry is a reliable methodology for whole blood cell phenotyping for different applications. The BD FACSLyric™ system comprises a flow cytometer available in different optical configurations, BD FACSuite™ Clinical software, and optional BD FACS™ Universal Loader. BD FACSuite Clinical software used with BD™ FC Beads and BD CS&T Beads enable universal setup for performance QC, instrument control, data acquisition/storage, online/offline data analysis, and instrument standardization. BD Biosciences sponsored the clinical evaluation of the BD FACSLyric 10-color configuration at seven clinical sites using delinked and de-identified blood specimens from HIV-infected and uninfected subjects to enumerate T-, B-, and NK-lymphocytes with the BD Multitest™ reagents (BD Multitest IMK kit and BD Multitest 6-color TBNK). Samples were analyzed on the BD FACSLyric system with BD FACSuite Clinical software, and on the BD FACSCanto™ II system with BD FACSCanto clinical software and BD FACS 7-Color Setup beads. For equivalency between methods, data (n = 362) were analyzed with Deming regression for absolute count and percentage of lymphocytes. Results gave R2 ≥0.98, with slope values ≥0.96, and slope ranges between 0.90-1.05. The percent (%) bias values were <10% for T- and NK cells and <15% for B- cells. The between-site (n = 4) total precision was tested for 5 days (2 runs/day), and gave %coefficient of variation below 10% for absolute cell counts. The stability claims were confirmed (n = 186) for the two BD Multitest reagents. The reference intervals were re-established in male and female adults (n = 134). The analysis by gender showed statistically significant differences for CD3+ and CD4+ T-cell counts and %CD4. In summary, the BD FACSLyric and the BD FACSCanto II systems generated comparable measurements of T-, B-, and NK-cells using BD Multitest assays.

Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study.

PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation). METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3). RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity. CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection. CLINICAL TRIAL REGISTRATION: NCT02188992.

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study.

PURPOSE: Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. METHODS: Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections. RESULTS: A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9. CONCLUSIONS: This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT02186522).

Human HLA-B27 typing using the BD™ HLA-B27 kit on the BD FACSVia™ system: A multicenter study.

The BD FACSVia™ system is a novel flow cytometer with improved workflow efficiencies. To evaluate the HLA-B27 application developed on the BD FACSVia system utilizing the BD™ HLA-B27 kit, we conducted a concordance study at three centers to compare with the BD FACSCalibur™ system. Prepared donor samples (n = 594) were analyzed on both the BD FACSVia and BD FACSCalibur for the HLA-B27 assay. Adjudication of HLA-B27 discordant results was performed using the reverse sequence-specific oligonucleotide (rSSO) DNA typing method (LABType® SSO, One Lambda). On the BD FACSVia system 80 B27 positive, 499 B27 negative and 15 "Inconclusive" samples were observed. The corresponding BD FACSCalibur results were 73 B27 positive, 502 B27 negative and 19 "gray zone" samples. The overall concordance of HLA-B27 determination was 98% between the two systems with seven more positives identified on BD FACSVia as compared to BD FACSCalibur. The equivocal zone between positive and negative on BD FACSVia (named "Inconclusive") and on BD FACSCalibur (named "gray zone") is due to antibody cross reactivity of HLA-B27 clone GS145.2. One negative sample verified with the rSSO DNA method was reported as HLA-B27 positive by the BD FACSVia system leading to a false positive result. Our study demonstrated concordance results between the BD FACSVia system and BD FACSCalibur. Intersite reproducibility of BD HLA-B27 assay remained within the limits of acceptability. © 2018 The Authors. Cytometry Part B: Clinical Cytometry published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.

Comparison of Flow Cytometric Methods for the Enumeration of Residual Leucocytes in Leucoreduced Blood Products: A Multicenter Study.

The BD FACSVia™ System features novel designs in hardware, software, and instrument QC. We compared the performance of the BD FACSVia System using the BD Leucocount™ kit with the BD FACSCalibur™ flow cytometer. Leucoreduced platelet (PLT, n = 252) and red blood cell (RBC, n = 278) specimens were enrolled at four sites. Each specimen was stained in four tubes using the BD Leucocount kit reagents and acquired on the two systems. BD Leucocount Control cells (high and low) were used to evaluate the inter-site reproducibility on the BD FACSVia System at three sites over 20 days. Deming regression and Bland-Altman analysis were performed to determine the WBC absolute counts on the BD FACSVia System vs. the BD FACSCalibur system. Assay accuracy for the range of 0-350 WBCs/µl was adequate. For samples with <25 WBCs/µl, the bias with 95% limits of agreement was 0.136 (-1.897 to 2.169) WBC/µl for PLTs (n = 184) and 0.170 (-2.025 to 2.365) WBC/µl for RBCs (n = 193). For inter-site reproducibility, the CV% was 6.46% (upper 95% CI 7.16%) for the PLT high control and 9.49% (10.52%) for the PLT low control. The CV% was 7.51% (8.32%) for the RBC high control and 10.76% (11.92%) for the RBC low control. The BD FACSVia System reported equivalent results of WBC absolute counts for leucoreduced PLT and RBC samples compared to the BD FACSCalibur system. The inter-laboratory reproducibility of the BD FACSVia System met study specifications. © 2018 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC.

Analytical Representations for Characterizing the Global Aviation Radiation Environment Based on Model and Measurement Databases.

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety climatological model and the Automated Radiation Measurements for Aerospace Safety (ARMAS) statistical database are presented as polynomial fit equations. Using equations based on altitude, L shell, and geomagnetic conditions an effective dose rate for any location from a galactic cosmic ray (GCR) environment can be calculated. A subset of the ARMAS database is represented by a second polynomial fit equation for the GCR plus probable relativistic energetic particle (REP; Van Allen belt REP) effective dose rates within a narrow band of L shells with altitudinal and geomagnetic dependency. Solar energetic particle events are not considered in this study since our databases do not contain these events. This work supports a suggestion that there may be a REP contribution having an effect at aviation altitudes. The ARMAS database is rich in Western Hemisphere observations for L shells between 1.5 and 5; there have been many cases of enhanced radiation events possibly related to effects from radiation belt particles. Our work identifies that the combined effects of an enhanced radiation environment in this L shell range are typically 15% higher than the GCR background. We also identify applications for the equations representing the Nowcast of Atmospheric Ionizing Radiation for Aviation Safety and ARMAS databases. They include (i) effective dose rate climatology in comparison with measured weather variability and (ii) climatological and statistical weather nowcasting and forecasting. These databases may especially help predict the radiation environment for regional air traffic management, for airport overflight operations, and for air carrier route operations of individual aircraft.

Clinical Evaluation of the BD FACSPresto™ Near-Patient CD4 Counter in Kenya.

BACKGROUND: The BD FACSPresto™ Near-Patient CD4 Counter was developed to expand HIV/AIDS management in resource-limited settings. It measures absolute CD4 counts (AbsCD4), percent CD4 (%CD4), and hemoglobin (Hb) from a single drop of capillary or venous blood in approximately 23 minutes, with throughput of 10 samples per hour. We assessed the performance of the BD FACSPresto system, evaluating accuracy, stability, linearity, precision, and reference intervals using capillary and venous blood at KEMRI/CDC HIV-research laboratory, Kisumu, Kenya, and precision and linearity at BD Biosciences, California, USA. METHODS: For accuracy, venous samples were tested using the BD FACSCalibur™ instrument with BD Tritest™ CD3/CD4/CD45 reagent, BD Trucount™ tubes, and BD Multiset™ software for AbsCD4 and %CD4, and the Sysmex™ KX-21N for Hb. Stability studies evaluated duration of staining (18-120-minute incubation), and effects of venous blood storage <6-24 hours post-draw. A normal cohort was tested for reference intervals. Precision covered multiple days, operators, and instruments. Linearity required mixing two pools of samples, to obtain evenly spaced concentrations for AbsCD4, total lymphocytes, and Hb. RESULTS: AbsCD4 and %CD4 venous/capillary (N = 189/ N = 162) accuracy results gave Deming regression slopes within 0.97-1.03 and R2 ≥0.96. For Hb, Deming regression results were R2 ≥0.94 and slope ≥0.94 for both venous and capillary samples. Stability varied within 10% 2 hours after staining and for venous blood stored less than 24 hours. Reference intervals results showed that gender-but not age-differences were statistically significant (p<0.05). Precision results had <3.5% coefficient of variation for AbsCD4, %CD4, and Hb, except for low AbsCD4 samples (<6.8%). Linearity was 42-4,897 cells/µL for AbsCD4, 182-11,704 cells/µL for total lymphocytes, and 2-24 g/dL for Hb. CONCLUSIONS: The BD FACSPresto system provides accurate, precise clinical results for capillary or venous blood samples and is suitable for near-patient CD4 testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT02396355.

Multivariate sexual selection on male song structure in wild populations of sagebrush crickets, Cyphoderris strepitans (Orthoptera: Haglidae).

While a number of studies have measured multivariate sexual selection acting on sexual signals in wild populations, few have confirmed these findings with experimental manipulation. Sagebrush crickets are ideally suited to such investigations because mating imposes an unambiguous phenotypic marker on males arising from nuptial feeding by females. We quantified sexual selection operating on male song by recording songs of virgin and mated males captured from three wild populations. To determine the extent to which selection on male song is influenced by female preference, we conducted a companion study in which we synthesized male songs and broadcast them to females in choice trials. Multivariate selection analysis revealed a saddle-shaped fitness surface, the highest peak of which corresponded to longer train and pulse durations, and longer intertrain intervals. Longer trains and pulses likely promote greater mate attraction, but selection for longer intertrain durations suggests that energetic constraints may necessitate "time outs". Playback trials confirmed the selection for longer train and pulse durations, and revealed significant stabilizing selection on dominant frequency, suggesting that the female auditory system is tightly tuned to the species-specific call frequency. Collectively, our results revealed a complex pattern of multivariate nonlinear selection characterized primarily by strong stabilizing and disruptive selection on male song traits.

Feasibility and safety study of a new device (Odón device) for assisted vaginal deliveries: study protocol.

BACKGROUND: Intrapartum complications are responsible for approximately half of all maternal deaths, and two million stillbirth and neonatal deaths per year. Prolonged second stage of labour is associated with potentially fatal maternal complications such as haemorrhage and infection and it is a major cause of stillbirth and newborn morbidity and mortality. Currently, the three main options for managing prolonged second stage of labour are forceps, vacuum extractor and caesarean section. All three clinical practices require relatively expensive equipment (e.g., a surgical theatre for caesarean section) and/or highly trained staff which are often not available in low resource settings. The specific aim of the proposed study is to test the safety and feasibility of a new device (Odón device) to effectively deliver the fetus during prolonged second stage of labour. The Odón device is a low-cost technological innovation to facilitate operative vaginal delivery and designed to minimize trauma to the mother and baby. These features combined make it a potentially revolutionary development in obstetrics, particularly for improving intrapartum care and reducing maternal and perinatal morbidity and mortality in low resource settings. METHODS/DESIGN: This will be a hospital-based, multicenter prospective phase 1 cohort study with no control group. Delivery with the Odón device will be attempted under normal labour and non-emergency conditions on all the women enrolled in the study. One-hundred and thirty pregnant women will be recruited in tertiary care facilities in Argentina. Safety will be assessed by examining maternal and infant outcomes until discharge. Feasibility will be evaluated by observing successful expulsion of the fetal head after one-time application of the device under standardized conditions (full cervical dilation, anterior presentation, +2 station, normal fetal heart rate). TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier: ACTRN12613000141741.

Pharmacokinetics and postprandial glycemic excursions following insulin lispro delivered by intradermal microneedle or subcutaneous infusion.

BACKGROUND: Intradermal (ID) delivery has been shown to accelerate insulin pharmacokinetics (PK). We compared the PK and pharmacodynamic (PD) effects of insulin lispro administered before two daily standardized solid mixed meals (breakfast and lunch), using microneedle-based ID or traditional subcutaneous (SC) delivery. METHOD: The study included 22 subjects with type 1 diabetes in an eight-arm full crossover block design. One arm established each subject's optimal meal dose. In six additional arms, the optimal, higher, and lower doses (+30%, -30%) were each given ID and SC delivery, in random order. The final arm assessed earlier timing for the ID optimal dose (-12 versus -2 min). The PK/PD data were collected for 6 h following meals. Intravenous basal regular insulin was given throughout, and premeal blood glucose (BG) adjusted to 115 mg/dl. RESULTS: The primary end point, postprandial time in range (70-180 mg/dl), showed no route-based differences with a high level of overall BG control for both SC and ID delivery. Secondary insulin PK end points showed more rapid ID availability versus SC across doses and meals (∆Tmax -16 min, ∆T50rising -7 min, ∆T50falling -30 min, all p < .05). Both intrasubject and intersubject variability for ID Tmax were significantly lower. Intradermal delivery showed modest, statistically significant secondary PD differences across doses and meals, generally within 90-120 min postprandially (∆12 mg/dl BG at 90 min, ∆7 mg/dl BGmax, ∆7 mg/dl mean BG 0-2 h, all p < .05). CONCLUSIONS: This study indicates that ID insulin delivery is superior to SC delivery in speed of systemic availability and PK consistency and may improve postprandial glucose control.

Non-invasive viability assessment of day-4 frozen-thawed human embryos using near infrared spectroscopy.

This study investigated if metabolomic profiling of culture media using near infrared (NIR) spectroscopy was related to live-birth rates after single-embryo transfer of frozen-thawed embryos. Analysis of culture media of frozen-thawed embryos was performed by NIR spectroscopy. A viability score was calculated using a predictive multivariate algorithm of fresh day-5 embryos with known pregnancy outcomes. This algorithm generated with fresh day-5 embryos could help to identify the live-birth group from the no live-birth group. Multivariable regression models that tested the predictive ability of the viability score for live birth showed an odds ratio in the crude analysis of 1.50 (P=0.008), after adjustment for embryo morphology, 1.44 (P=0.022), and after adjustment for all variables, 1.71 (P=0.005); based on a 0.1 step increase in viability scores. In conclusion, higher viability scores resulted in higher live-birth rates. An algorithm generated from fresh embryos might be used to predict viability of frozen-thawed embryos. Frozen-thawed embryos have different metabolic activity which is related to implantation potential. Therefore, this method might be useful to select the best embryo for transfer within a group of embryos with similar morphology.

Continuous glucose monitoring using a novel glucose/galactose binding protein: results of a 12-hour feasibility study with the becton dickinson glucose/galactose binding protein sensor.

AIM: This study evaluated the performance characteristics of a prototype Becton Dickinson (BD) (Franklin Lakes, NJ) glucose/galactose binding protein (GGBP) sensor placed intradermally (BD-ID) or subcutaneously (BD-SC) for continuous glucose monitoring. MATERIALS AND METHODS: The performance characteristics of the prototype BD GGBP sensor after intradermal or subcutaneous placement were assessed, and its accuracy was compared with that of a glucose oxidase (GOx)-based sensor and a standard laboratory method (YSI STAT2300 analyzer, Yellow Springs Instrument, Yellow Springs, OH) under glucose clamp conditions and during an off-clamp meal challenge in 40 patients with type 1 or 2 diabetes in a 12-h feasibility study. RESULTS: BD-ID and BD-SC sensors performed as well as or better than the GOx-based sensor (differences in median absolute percentage error 2-4 points in hyperglycemic and euglycemic regions, ≥ 10 points in the hypoglycemic region). For glucose values ≤ 100 mg/dL, the percentage of measurement values in consensus error plot Zone A was substantially higher with the GGBP sensors than the GOx-based sensor. CONCLUSIONS: The BD prototype sensor demonstrated competitive accuracy relative to a GOx-based sensor and a YSI blood standard with a single calibration and minimal warm-up. Current development work is focused on the design and manufacture of a commercially feasible device that will include marked enhancements to device robustness and longevity.

Receiver operating characteristic (ROC) analysis of day 5 morphology grading and metabolomic Viability Score on predicting implantation outcome.

PURPOSE: Assessment of embryo viability is a key component of in vitro fertilization (IVF) and currently relies largely on embryo morphology and cleavage rate. In this study, we used receiver operating characteristic (ROC) analysis to compare the Viability Score (generated by metabolomic profiling of spent embryo culture media using near infrared (NIR) spectroscopy) to morphologic grading for predicting pregnancy in women undergoing single embryo transfer (SET) on day 5. METHODS: A total of 198 spent embryo culture media samples were collected in four IVF centers located in the USA, Europe and Australia. First, 137 samples (training set) were analyzed by NIR to develop an algorithm that generates a Viability Score predictive of pregnancy for each sample. Next, 61 samples (validation set) were analyzed by observers blinded to embryo morphology and IVF outcome, using the Day 5 algorithm generated with the training set. Pregnancy was defined as fetal cardiac activity (FCA) at 12 weeks of gestation. RESULTS: The Area Under the Curve (AUC) was greater for the metabolomic Viability Score compared to Morphology [Training set: 0.75 versus 0.55, p = 0.0011; Validation set: 0.68 versus 0.50, P = 0.021], and for a Composite score (obtained using a model combining Viability Score with morphologic grading), compared to morphology alone [0.74 versus 0.50, p = 0.004]. CONCLUSIONS: Our findings suggest that Viability Score alone or in combination with morphologic grading has the potential to be a better classifier for pregnancy outcome than morphology alone in women undergoing SET on day 5.

Evidence for male allocation in pipefish?

Sexual differences in the extent and type of parental care lie at the heart of sexual selection theory, and evolution resulting from parental conflict has produced some striking behavioural and morphological adaptations. In a study of male pregnancy in Gulf pipefish, Paczolt and Jones showed that more eggs were transferred to the male's brood pouch and more offspring survived following mating with large females (preferred by males) than with small (less preferred) females. Although the authors conclude that the lower survival of embryos from small females is most consistent with males actively removing resources from these offspring, no data are presented to directly support this hypothesis (ref. 2, and Supplementary Information therein) and the data do not refute the alternative explanation that differential egg survival is caused by female effects mediated by variation in fecundity and egg size or quality. We argue that only by experimentally manipulating female attractiveness separately from the quality of eggs deposited in the brood pouch can the extent of sexual conflict in this role-reversed system be assessed.

Male weaponry in a fighting cricket.

Sexually selected male weaponry is widespread in nature. Despite being model systems for the study of male aggression in Western science and for cricket fights in Chinese culture, field crickets (Orthoptera, Gryllidae, Gryllinae) are not known to possess sexually dimorphic weaponry. In a wild population of the fall field cricket, Gryllus pennsylvanicus, we report sexual dimorphism in head size as well as the size of mouthparts, both of which are used when aggressive contests between males escalate to physical combat. Male G. pennsylvanicus have larger heads, maxillae and mandibles than females when controlling for pronotum length. We conducted two experiments to test the hypothesis that relatively larger weaponry conveys an advantage to males in aggressive contests. Pairs of males were selected for differences in head size and consequently were different in the size of maxillae and mandibles. In the first experiment, males were closely matched for body size (pronotum length), and in the second, they were matched for body mass. Males with proportionately larger weaponry won more fights and increasing differences in weaponry size between males increased the fighting success of the male with the larger weaponry. This was particularly true when contests escalated to grappling, the most intense level of aggression. However, neither contest duration nor intensity was related to weaponry size as predicted by models of contest settlement. These results are the first evidence that the size of the head capsule and mouthparts are under positive selection via male-male competition in field crickets, and validate 800-year-old Chinese traditional knowledge.

Sensitivity of Raman spectra to chemical functional groups.

Spectral features in Raman spectra of organic molecules can be attributed to certain functional groups. A library of 1222 Raman spectra was used to train an artificial neural network (ANN) for predicting the presence of 13 functional groups. Sensitivity analysis was applied to the ANN models to determine a sensitivity factor or feature spectrum for each functional group. The feature spectra could then be used to predict the presence of specific groups based on Bayes' theorem. Once a model is constructed for each functional group, it can be applied directly to measured spectra of structurally unknown molecules and provide real-time predictions. Prediction accuracies of greater than 90% were obtained for aromatic, alkene, aldehyde, ketone, ester, nitro, and nitrile linkages. Accuracies for alcohols and amines were in the 80% range.