Polymorphism of growth hormone (GH) gene and its association with performance and body conformation of Harnali sheep.

The present study was carried out to study the polymorphism in the GH gene and its association with various performance and body conformation traits, viz., birth weight (B-WT), weaning weight (W-WT), six-month body weight (6 M-WT), one-year body weight (Y-WT), annual greasy fleece weight (AGFW), body length (BL), body height (BH), heart girth (HG) and paunch girth (PG) in 138 Harnali sheep. PCR-RFLP was performed to identify polymorphism in the targeted region of the GH gene. The PCR product of 422 bp size of the GH gene was amplified encompassing partial exon 2 and inton 3 in Harnali sheep. The PCR product was digested with HaeIII restriction enzyme for the detection of Single nucleotide polymorphism (SNP). The digested products revealed the presence of two genotypes, i.e. AA and AB in the studied population. A > G mutation (A781G) was observed in our resource population. The AA genotype was found to be the predominant genotype (0.62). Chi square value revealed that resource population was not under Hardy-Weinberg equilibrium with respect to target locus. Period of birth was found to have significant effect on W-WT, Y-WT, BL, BH and PG. Sex of animal was found to have significant (P < 0.05) effect on W-WT and highly significant (P < 0.01) effect on 6 M-WT, Y-WT and AGFW in Harnali sheep. The effect of genotype was found to be significant (P < 0.05) on annual greasy fleece weight. AB genotype was found to be associated with higher annual greasy fleece weight and can be used as a potential candidate marker in selection criteria for improving greasy fleece weight in Harnali sheep.

Multi-oligomeric and catalytically compromised serine acetyltransferase and cysteine regulatory complex of Mycobacterium tuberculosis.

l-cysteine, a primary building block of mycothiol, plays an essential role in the defense mechanism of Mycobacterium tuberculosis (Mtb). However, it is unclear how Mtb regulates cysteine biosynthesis as no study has reported the cysteine regulatory complex (CRC) in Mtb. Serine acetyltransferase (SAT) and cysteine synthase (CS) interact to form CRC. Although MtCS has been characterized well, minimal information is available on MtSAT, which synthesizes, O-acetylserine (OAS), the precursor of cysteine. This study fills the gap and provides experimental evidence for the presence of MtCRC and a non-canonical multi-oligomeric MtSAT. We employed multiple analytical methods to characterize the oligomeric and kinetic properties of MtSAT and MtCRC. Results show that MtSAT, lacking >75 N-terminal amino acids exists in three different assembly states; trimer, hexamer, and dodecamer, compared to the single hexameric state of SAT of other bacteria. While hexamers display the highest catalytic turnover, the trimer is the least active. The predominance of trimers at low physiologically relevant concentrations suggests that MtSAT displays the lowest catalytic potential known. Further, the catalytic potential of MtSAT is also significantly reduced in CRC state, in contrast to enhanced activity of SAT in CRC of other organisms. Our study provides insights into multi-oligomeric MtSAT with reduced catalytic potential and demonstrates that both MtSAT and MtCS of Mycobacterium interact to form CRC, although with altered catalytic properties. We discuss our results in light of the altered biochemistry of the last step of canonical sulfate-dependent cysteine biosynthesis of Mycobacterium.

Unearthing the genotype-inhibitor phenotype association in severe haemophilia A: A north Indian cohort study.

INTRODUCTION: Various risk factors for inhibitor development in haemophilia A (HA) have been described but Indian data remains scanty. AIM: We aimed to evaluate the genetic changes in Indian HA-patients that are associated with the development of inhibitors. METHODS: All HA-patients with inhibitors who availed coagulation-laboratory services from January-2015 till December-2021 and had their samples preserved for DNA extraction were included in this study. An equal number of severity-matched HA patients without inhibitors were also included as controls. Intron 22 and intron 1 inversions in Factor VIII gene were identified using inverse-shifting-PCR. Inversion-negative patients were further assessed by targeted NGS, MLPA. RESULTS: Thirty HA-patients with inhibitors were identified. All had severe-HA. Thirty severe-HA-patients without inhibitors were also included as controls. Intron 22 inversion (63.3%) and large deletions (15%) were the commonest variants identified. There was no difference in genetic variants in patients with low and high titre inhibitors. A3, A2 and C2 were the most common domains involved in inversion-negative patients with inhibitors. However, there was no significant difference in domain involvement among inversion-negative patients with and without inhibitors. Seven novel-variants were identified, including three large deletions, one large duplication and two nonsense variants in inhibitor-positive patients, and one frameshift variant in inhibitor-negative patient. After adjusting for clinical risk-factors, large deletions were independently associated with the presence of inhibitors [aOR:6.1 (1.41-56.3)]. CONCLUSION: Intron 22 inversions are the commonest variant in Indian patients with severe-HA. Large deletions predispose to inhibitor development independent of clinical risk factors.

Effect of Covid pandemic on immunization status of children in tertiary care Hospital of North India: reason for partial and non-immunization a cross-sectional study.

BACKGROUND: Low immunization coverage in India attributes to many factors including sociodemographic factors and people's behavior. COVID-19 pandemic resulted in disruptions in achieving optimum availability and utilization of immunization services. This study was carried out to find out the immunization status of children in the post COVID era and various factors responsible for non-immunization during the pandemic. METHODS: This cross-sectional study included parents of 225 admitted children aged 1-6 years were interviewed using a semi-structured open-ended questionnaire. Children were classified as completely immunized, partially immunized and unimmunized on the basis of vaccines missed given under first year of life. Reasons for non-immunization and delay/missed vaccination during COVID-19 pandemic were recorded. RESULTS: Of the 225 children, 162 (72%; 95% CI 66-78%) were completely immunized, 55 (24.4%; 95% CI 19-30%) were partially immunized and 8 (3.6%; 95% CI 1-6%) were unimmunized. Parents with hospital deliveries, higher education level and lesser birth order were more likely to have children with better immunization status (p < 0.05). First dose of measles scheduled at 9 months and 3rd dose of pentavalent vaccine/OPV/Rotavirus vaccine scheduled at 14 weeks were most commonly missed vaccines among partially immunized. Lack of awareness (n = 36, 57.1%; 95% CI 45-70%) was the common reason for partial and non-immunization followed by illness of child (n = 21, 33.3%; 95% CI 21-45%) and COVID-19 pandemic (n = 11, 17.4%; 95% CI 8-27%). Pandemic was reason for delay in 50 (22.2%; 95% CI 17-28%) children. Restrictions of movement (64%; 95% CI 50-78%), fear of being exposed to COVID-19 (52%; 95% CI 38-66%) were the most common reasons for delay during the pandemic. Of the 50 children who had delay due to pandemic, 39 children (17.3%; 95% CI 12-22%) received their catch-up immunization after the pandemic. No child remained completely unimmunized due to COVID-19 pandemic. CONCLUSIONS: Although COVID-19 pandemic resulted in disruptions in routine immunization services, sociodemographic factors such as awareness for immunization, parental education and various beliefs for immunization were responsible for the children remaining unimmunized or partially immunized after the pandemic.

Protein S antibody as an adjunct therapy for hemophilia B.

ABSTRACT: Hemophilia B (HB) is caused by an inherited deficiency of plasma coagulation factor IX (FIX). Approximately 60% of pediatric patients with HB possess a severe form of FIX deficiency (<1% FIX activity). Treatment typically requires replacement therapy through the administration of FIX. However, exogenous FIX has a limited functional half-life, and the natural anticoagulant protein S (PS) inhibits activated FIX (FIXa). PS ultimately limits thrombin formation, which limits plasma coagulation. This regulation of FIXa activity by PS led us to test whether inhibiting PS would extend the functional half-life of FIX and thereby prolong FIX-based HB therapy. We assayed clotting times and thrombin generation to measure the efficacy of a PS antibody for increasing FIX activity in commercially obtained plasma and plasma from pediatric patients with HB. We included 11 pediatric patients who lacked additional comorbidities and coagulopathies. In vivo, we assessed thrombus formation in HB mice in the presence of the FIXa ± PS antibody. We found an accelerated rate of clotting in the presence of PS antibody. Similarly, the peak thrombin formed was significantly greater in the presence of the PS antibody, even in plasma from patients with severe HB. Furthermore, HB mice injected with PS antibody and FIX had a 4.5-fold higher accumulation of fibrin at the thrombus induction site compared with mice injected with FIX alone. Our findings imply that a PS antibody would be a valuable adjunct to increase the effectiveness of FIX replacement therapy in pediatric patients who have mild, moderate, and severe HB.

Unusual Perineal Metastasis in a Case of Prostate Cancer on 68 Ga-PSMA-11 PET/CT.

ABSTRACT: Prostate cancer is the fifth leading cause of death in the male population worldwide. 68 Ga-PSMA PET/CT has proved to be an excellent modality with greater accuracy for nodal and bone/visceral metastases staging than bone scintigraphy and CT scan, with high sensitivity and specificity. Common sites of metastasis include bone (84%), lymph nodes (10.6%), liver (10.2%), lung, and pleura (9.1%); however, metastasis to the skin is quite rare (≤0.36%). The present case demonstrates PSMA-avid perineal metastasis in a patient of prostate cancer postchemoradiotherapy on 68 Ga-PSMA PET/CT scan.

Factors associated with thrombo-hemorrhagic deaths in patients with Acute Promyelocytic leukemia treated with Arsenic Trioxide and all-trans retinoic acid.

Acute Promyelocytic Leukemia (APL) is associated with excellent long-term outcomes. However, early mortality due to coagulopathy remains a challenge. In this study we examined the bleeding and thrombotic manifestations, as well as incidence of Early Death secondary to thrombosis/hemorrhage (ED-TH) in patients with APL. Early death (ED) was defined as death occurring within 30 days of induction therapy. Two-hundred forty-eight patients were included in the study. Overall, 57 patients had evidence of a major bleed/thrombosis at presentation or during induction therapy, including 44 patients with a major bleed, 8 patients with thrombosis and 5 patients with both evidence of thrombosis and a major bleed. Forty patients (16.1%) had ED, of which 21 had ED-TH. The cumulative incidence of death due to thrombo-hemorrhagic complications at 30 days was 8.4%. On univariate analysis, increasing Prothrombin time (PT)(p-<0.001), white blood cell count (p < 0.001) and activated Partial thromboplastin time (aPTT) (p < 0.001) were statistically significantly associated with increased risk of ED-TH. However, on multivariate analysis, only increasing PT (p-0.025) and aPTT (p-0.041) were significantly associated with increased risk of ED-TH.

Balancing growth amidst salt stress - lifestyle perspectives from the extremophyte model Schrenkiella parvula.

Schrenkiella parvula, a leading extremophyte model in Brassicaceae, can grow and complete its lifecycle under multiple environmental stresses, including high salinity. Yet, the key physiological and structural traits underlying its stress-adapted lifestyle are unknown along with trade-offs when surviving salt stress at the expense of growth and reproduction. We aimed to identify the influential adaptive trait responses that lead to stress-resilient and uncompromised growth across developmental stages when treated with salt at levels known to inhibit growth in Arabidopsis and most crops. Its resilient growth was promoted by traits that synergistically allowed primary root growth in seedlings, the expansion of xylem vessels across the root-shoot continuum, and a high capacity to maintain tissue water levels by developing thicker succulent leaves while enabling photosynthesis during salt stress. A successful transition from vegetative to reproductive phase was initiated by salt-induced early flowering, resulting in viable seeds. Self-fertilization in salt-induced early flowering was dependent upon filament elongation in flowers otherwise aborted in the absence of salt during comparable plant ages. The maintenance of leaf water status promoting growth, and early flowering to ensure reproductive success in a changing environment, were among the most influential traits that contributed to the extremophytic lifestyle of S. parvula.

Tobacco use and its impact on survival in young patients with oral cancer.

Background: Tobacco is a major risk factor associaetd with developing oral factor. Recent studies have shown that the age of onset, especially in Asia, is reducing. This study was to determine if tobacco exposure correlated with prognosis in oral squamous cell carcinoms (OSCC) based on age at diagnosis. Methods: Six hundred and forty three patients of OSCC treated in our institution were divided into four groups, younger patients (≤45 years) with or without tobacco exposure and older patients (>45 years) with or without tobacco exposure, and compared with respect to prognostically relevant variables, disease-free survival (DFS) and overall survival (OS). Survival analysis was performed. Results: The percentage of those with tobacco exposure was comparable in both age groups. Tobacco correlated with known pathological determinants in OSCC; however, perineural invasion, lymphovascular invasion, and extranodal extension were significantly more common in the young. On survival analysis, tobacco exposure impacted OS (P = 0.04) and DFS (P = 0.03) in patients ≤45 years, and not in older patients >45 years. On multivariate analysis, tobacco exposure in the young was significantly associated with recurrence (P = 0.03, hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.07-2.94) but not survival. Conclusion: Younger patients with a history of tobacco use have a significantly higher risk of recurrence and mortality due to OSCC, but this difference could not be attributed to any of the known prognostic determinants in OSCC. Younger patients also had more adverse pathological features. Whether this occurs because of altered disease biology or pathways of carcinogenesis in the young with tobacco exposure is unknown. Younger tobacco users with oral cancer are more likely to have a poor prognosis.

Correction to: Genetic Spectrum in F13A1 Detected by Next-Generation Sequencing Among North Indian Patients with FXIII Deficiency.

[This corrects the article DOI: 10.1007/s12288-022-01579-1.].

Ferromagnetism in Defected TMD (MoX2, X = S, Se) Monolayer and Its Sustainability under O2, O3, and H2O Gas Exposure: DFT Study.

Spin-polarized density-functional theory (DFT) has been employed to study the effects of atmospheric gases on the electronic and magnetic properties of a defective transition-metal dichalcogenide (TMD) monolayer, MoX2 with X = S or Se. This study focuses on three single vacancies: (i) molybdenum "VMo"; (ii) chalcogenide "VX"; and (iii) di-chalcogenide "VX2". Five different samples of sizes ranging from 4 × 4 to 8 × 8 primitive cells (PCs) were considered in order to assess the effect of vacancy-vacancy interaction. The results showed that all defected samples were paramagnetic semiconductors, except in the case of VMo in MoSe2, which yielded a magnetic moment of 3.99 µB that was independent of the sample size. Moreover, the samples of MoSe2 with VMo and sizes of 4 × 4 and 5 × 5 PCs exhibited half-metallicity, where the spin-up state becomes conductive and is predominantly composed of dxy and dz2 orbital mixing attributed to Mo atoms located in the neighborhood of VMo. The requirement for the establishment of half-metallicity is confirmed to be the provision of ferromagnetic-coupling (FMC) interactions between localized magnetic moments (such as VMo). The critical distance for the existence of FMC is estimated to be dc≅ 16 Å, which allows small sample sizes in MoSe2 to exhibit half-metallicity while the FMC represents the ground state. The adsorption of atmospheric gases (H2O, O2, O3) can drastically change the electronic and magnetic properties, for instance, it can demolish the half-metallicity characteristics. Hence, the maintenance of half-metallicity requires keeping the samples isolated from the atmosphere. We benchmarked our theoretical results with the available data in the literature throughout our study. The conditions that govern the appearance/disappearance of half-metallicity are of great relevance for spintronic device applications.

Ex Vivo Colonic Tissue Susceptibility to HIV-1 in Cisgender Men and Women.

The biology of HIV-1 acquisition through unprotected receptive anal intercourse is understudied. Considering that sex hormones are implicated in intestinal physiology, pathology, and HIV acquisition and pathogenesis, we explored links between sex hormones, ex vivo HIV-1BaL infection of colonic mucosa, and candidate biomarkers of susceptibility to HIV-1 (CD4+ T cell frequencies and immune mediators) in cisgender women and men. No consistent significant associations between sex hormone concentrations and ex vivo tissue infection with HIV-1BaL were detected. In men, serum estradiol (E2) concentrations were positively associated with tissue proinflammatory mediators (IL17A, GM-CSF, IFNγ, TNFα, and MIG/CXCL9) and serum testosterone concentrations were negatively associated with frequencies of activated CD4+ T cells (CD4+CCR5+, CD4+HLA-DR+, and CD4+CD38+HLA-DR+). In women, the only significant interactions were positive associations between progesterone (P4)/E2 ratios and tissue ILRA concentrations and between P4/E2 ratios and frequencies of tissue CD4+α4ß7high+ T cells. The study did not reveal relationships between biological sex or phase of the menstrual cycle and ex vivo tissue HIV-1BaL infection and tissue immune mediators. A comparison of CD4+ T cell frequencies between study groups revealed a higher frequency of tissue CD4+α4ß7high+ T cells in women versus men. In contrast, higher frequencies of tissue CD4+CD103+ T cells were detected in men versus women in the follicular phase of the menstrual cycle. Overall, the study identified associations between systemic sex hormone concentrations, biological sex, and tissue candidate biomarkers of susceptibility to HIV-1. The significance of these results for tissue susceptibility to HIV-1 and early HIV-1 pathogenesis warrants further investigation.

Genetic Spectrum in F13A1 Detected by Next-Generation Sequencing Among North Indian Patients with FXIII Deficiency.

Purpose: The study aimed to explore the molecular defects underlying FXIII deficiency. Materials and Methods: Sixteen unrelated cases were enrolled based on the indication of the urea clot solubility test and Factor XIII-A antigen levels. Cases were further subjected to targeted next-generation sequencing (custom gene panel: F7, F8, VWF, F9, F13A1, F13B). The pathogenic/likely pathogenic variants were validated by Sanger sequencing in the patients and family members. Results: Mean age of referral to our center was 27.2 years (8 week-67 years). Consanguinity was found in only one of the 16 cases and 9 cases presented in infancy. The most common symptoms were skin bleeds (69%) and umbilical cord bleed (50%). The clot solubility test was positive in 12, inconclusive in 1, and normal in 3. Mean FXIII-A levels were 15.7 IU/dL (range 0.6 to 49.5 IU/dL). Pathogenic/likely pathogenic variants in F13A1 were found in 11 (69%). Nine cases (82%) were homozygous, and two were compound heterozygous. Total eleven variants were found of which four were missense (c.1226G>A; c.998C>T; c.631G>C; c.2134A>C); three deletion (c.521delG; c.742delA; c.1405_1408delCAAA); two nonsense (c.1112G>A; c.1127G>A) and two splice site (c.1909-1G>C; c.2045G>A). No probably pathogenic variant was found in the F13B. Conclusion: Inherited FXIII deficiency with bleeding is associated with genetic defects in predominantly the F13A1 gene. A variety of variants were seen in this cohort. A nonsense variant c.1127G>A found in three of our cases seems to be recurrent. This data will contribute to designing functional studies and antenatal testing in affected families. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01579-1.

Dissemination of carbapenemase-producing Enterobacterales in Ireland from 2012 to 2017: a retrospective genomic surveillance study.

The spread of carbapenemase-producing Enterobacterales (CPE) is of major public health concern. The transmission dynamics of CPE in hospitals, particularly at the national level, are not well understood. Here, we describe a retrospective nationwide genomic surveillance study of CPE in Ireland between 2012 and 2017. We sequenced 746 national surveillance CPE samples obtained between 2012 and 2017. After clustering the sequences, we used thresholds based on pairwise SNPs, and reported within-host diversity along with epidemiological data to infer recent putative transmissions. All clusters in circulating clones, derived from high-resolution phylogenies, of a species (Klebsiella pneumoniae, Escherichia coli, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter hormaechei and Citrobacter freundii) were individually examined for evidence of transmission. Antimicrobial resistance trends over time were also assessed. We identified 352 putative transmission events in six species including widespread and frequent transmissions in three species. We detected putative outbreaks in 4/6 species with three hospitals experiencing prolonged outbreaks. The bla OXA-48 gene was the main cause of carbapenem resistance in Ireland in almost all species. An expansion in the number of sequence types carrying bla OXA-48 was an additional cause of the increasing prevalence of carbapenemase-producing K. pneumoniae and E. coli.

Impact of ABO blood group antigens on residual factor VIII levels and risk of inhibitor development in hemophilia A.

Background: The clinical phenotype of hemophilia A (HA) does not always correlate with severity. Similarly, the presence of inhibitors does not necessarily increase the risk of bleeding. This paradox between clinical and laboratory findings may be partially attributed to non-modifiable factors, such as blood group, which is known to influence FVIII levels in healthy individuals. Our aim was to assess the effect of ABO blood group antigens on FVIII levels across the severity spectrum of HA and risk of inhibitor development. Methods: Data of consecutive patients with HA who visited the coagulation unit of a northern Indian tertiary care hospital between 2010‒2021 were reviewed. Patients with missing blood group data, transfusion histories, or baseline FVIII levels were excluded. Results: Mild, moderate, and severe HA was present in 41 (6.9%), 72 (12.2%), and 479 (80.9%) patients, respectively. There were no differences in the FVIII levels among the various blood groups across the HA severity spectrum. Inhibitors were administered to 35 patients (5.9%). In the multivariate analysis, blood group A was an independent risk factor for the development of inhibitors (adjusted odds ratio 2.70, P=0.04) after adjusting for age at onset of bleeding, FVIII transfusion, age at first FVIII transfusion, and severity of HA. Conclusion: Unlike what is observed in healthy individuals, blood group did not influence residual FVIII levels across the severity spectrum of HA. Patients in group A had a higher risk of developing inhibitors.

Comparative genomic epidemiology of serotype 3 IPD and carriage isolates from Southampton, UK between 2005 and 2017.

Serotype 3 pneumococci remains a significant cause of disease despite its inclusion in PCV13. Whilst clonal complex 180 (CC180) represents the major clone, recent studies have refined the population structure into three clades: Iα, Iß and II, with the last being a recent divergent and more antibiotic-resistant. We present a genomic analysis of serotype 3 isolates from paediatric carriage and all-age invasive disease, collected between 2005 and 2017 in Southampton, UK. Forty-one isolates were available for analysis. Eighteen were isolated during the annual cross-sectional surveillance of paediatric pneumococcal carriage. The remaining 23 were isolated from blood/cerebrospinal fluid specimens at the University Hospital Southampton NHS Foundation Trust laboratory. All carriage isolates were CC180 GPSC12. Greater diversity was seen with invasive pneumococcal disease (IPD) with three GPSC83 (ST1377: n=2, ST260: n=1) and one GPSC3 (ST1716). For both carriage and IPD, Clade Iα was dominant (94.4 and 73.9 % respectively). Two isolates were Clade II with one from carriage (a 34-month-old, October 2017) and one invasive isolate (49-year-old, August 2015). Four IPD isolates were outside the CC180 clade. All isolates were genotypically susceptible to penicillin, erythromycin, tetracycline, co-trimoxazole and chloramphenicol. Two isolates (one each from carriage and IPD; both CC180 GPSC12) were phenotypically resistant to erythromycin and tetracycline; the IPD isolate was also resistant to oxacillin.In the Southampton area, carriage and invasive disease associated with serotype 3 is predominantly caused by Clade Iα CC180 GPSC12.

The NIN-LIKE PROTEIN 7 transcription factor modulates auxin pathways to regulate root cap development in Arabidopsis.

The root cap is a small tissue located at the tip of the root with critical functions for root growth. Present in nearly all vascular plants, the root cap protects the root meristem, influences soil penetration, and perceives and transmits environmental signals that are critical for root branching patterns. To perform these functions, the root cap must remain relatively stable in size and must integrate endogenous developmental pathways with environmental signals, yet the mechanism is not clear. We previously showed that low pH conditions altered root cap development, and these changes are mediated by the NIN LIKE PROTEIN 7 (NLP7) transcription factor, a master regulator of nitrate signaling. Here we show that in Arabidopsis NLP7 integrates nitrate signaling with auxin pathways to regulate root cap development. We found that low nitrate conditions promote aberrant release of root cap cells. Nitrate deficiency impacts auxin pathways in the last layer of the root cap, and this is mediated in part by NLP7. Mutations in NLP7 abolish the auxin minimum in the last layer of the root cap and alter root cap expression of the auxin carriers PIN-LIKES 3 (PILS3) and PIN-FORMED 7 (PIN7) as well as transcription factors that regulate PIN expression. Together, our data reveal NLP7 as a link between endogenous auxin pathways and nitrate signaling in the root cap.

Cherenkov Radiation in Optical Fibres as a Versatile Machine Protection System in Particle Accelerators.

Machine protection systems in high power particle accelerators are crucial. They can detect, prevent, and respond to events which would otherwise cause damage and significant downtime to accelerator infrastructure. Current systems are often resource heavy and operationally expensive, reacting after an event has begun to cause damage; this leads to facilities only covering certain operational modes and setting lower limits on machine performance. Presented here is a new type of machine protection system based upon optical fibres, which would be complementary to existing systems, elevating existing performance. These fibres are laid along an accelerator beam line in lengths of ∼100 m, providing continuous coverage over this distance. When relativistic particles pass through these fibres, they generate Cherenkov radiation in the optical spectrum. This radiation propagates in both directions along the fibre and can be detected at both ends. A calibration based technique allows the location of the Cherenkov radiation source to be pinpointed to within 0.5 m with a resolution of 1 m. This measurement mechanism, from a single device, has multiple applications within an accelerator facility. These include beam loss location monitoring, RF breakdown prediction, and quench prevention. Detailed here are the application processes and results from measurements, which provide proof of concept for this device for both beam loss monitoring and RF breakdown detection. Furthermore, highlighted are the current challenges for future innovation.

New approaches for developing biomarkers of hormonal contraceptive use.

To identify biomarkers of hormonal contraceptive (HC) use in urine and saliva, we conducted a pilot study with 30 women initiating levonorgestrel (LNG) containing combined oral contraceptives (COCs) or depot medroxyprogesterone acetate (DMPA) (15/group). Based on established COC pharmacokinetics, we collected serum and urine samples before COC ingestion and during Days one and three of use, or before DMPA injection and on Days 21 and 60 post-injection. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure serum/urine LNG and MPA. LNG was undetectable at baseline (specificity 100%); post ingestion, most urine samples had detectable LNG levels (sensitivity: 80% 6 h post Dose one, 93% 6 h post Dose three). We used a DetectX LNG immunoassay kit and showed 100% sensitivity measuring urine LNG. Urine MPA levels were undetectable in 14/15 women at baseline (specificity 91%); post-injection all urine samples had detectable MPA levels (sensitivity: 100% days 21 and 60). Results suggest urine sampling can be used to identify a biomarker of LNG and MPA use. Based on evidence from other steroidal hormonal studies showing changes affecting the transcriptome profile of saliva at 24 h, we used the same (COC, DMPA) timepoints to collect saliva. We performed transcriptome analysis and detected several differentially expressed genes in DMPA users' saliva on Days 21 and 60 compared to baseline; none among COC users. We plan further research of differential gene expression in saliva as a HC biomarker of DMPA use, and will explore longer periods of COC use and saliva collection times, and application of microRNA sequencing to support using saliva as a COC biomarker.