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Adolescent-friendly health services in Nepal: usage and key determinants
Get PDFBackground: Adolescent-Friendly Health Services (AFHS) are crucial for addressing the sexual and reproductive health needs of adolescents. Despite AFHS integration into public health facilities in Nepal since 2009, the utilization of these services remains suboptimal and concerning. The purpose of this study was to investigate the utilization and key determinants of AFHS in Pokhara, Nepal. Methods: An analytical quantitative study involving 569 adolescents aged 12–19 years was conducted from July 12 to October 25, 2023. Study participants were selected using simple random sampling and proportionate stratified sampling methods. The study utilized a self-administered questionnaire, and key determinants of AFHS usage were identified using logistic regression analyses. Results: The mean age of the participants was 14.66 ± 1.09 years. Only 37.1% of the adolescents had utilized AFHS at the time of the study. More than half of the participants (51.7%) mentioned the need for AFHS. The key determinants of AFHS utilization were: perceived healthcare need as seeking health facilities directly (AOR: 1.62, 95% CI: 1.07–2.46, vs. seeking care after home remedies); hospital as the first treatment point (AOR: 2.50, 95% CI: 1.68–3.72, vs. grassroots health facilities); perceived need for AFHS (AOR: 1.57, 95% CI: 1.06–2.33); not paying for AFHS (AOR: 2.06, 95% CI: 1.39–3.04), feasible service time (AOR: 1.51, 95% CI: 1.02–2.46); proper counselling services (AOR: 1.97, 95% CI: 1.19–3.26); and adequacy of AFHS facilities (adequate water supply and sanitation facilities, AOR: 1.70, 95% CI: 1.12–2.58). Conclusions: The utilization of AFHS remains low within the study population. Key factors influencing AFHS utilization include perceived healthcare need, the first point of treatment, payment for services, perceived necessity of AFHS, service time feasibility, availability of counselling services, and access to reliable water supply and sanitation facilities. Therefore, it is crucial to establish proper infrastructure, implement effective planning, allocate adequate budgets, train personnel, and provide comprehensive counselling services tailored to adolescents’ needs to ultimately enhance AFHS utilization. Clinical trial number: Not applicable
Individual identification of bony fishes using unique body markings: implications and applications
No full textThe natural variation in animal body markings, such as spots, stripes, and blotches, offers a powerful tool for researchers, conservationists, citizen scientists, and resource managers to distinguish specific individuals within species. By building libraries of photo-identified individuals, we can track and differentiate individuals over time and space, thereby non-invasively and often cost-effectively studying species' biology and behaviour. This, in turn, enhances our understanding of species’ ecological roles, and informs and supports effective conservation strategies. Although photo-identification has been successfully applied to various aquatic species, including cetaceans, sharks, and rays, it remains surprisingly underutilised for bony fishes. Indeed, despite their striking diversity of colours and patterns, relatively few studies have used natural markings to non-invasively investigate bony fish biology and conservation. In this review, we highlight the potential of photo-identification as a valuable research and management tool for these fishes in both field and laboratory environments. We outline the scientific, practical and ethical benefits of this approach, illustrating how individual identification can advance our understanding of fish biology and support their conservation efforts. We also discuss previous applications of photo-identification in bony fishes, examine barriers to its broader adoption, and address common misconceptions that may limit its use. We propose strategies to overcome these challenges, driven by advancements in camera technology and artificial intelligence, and discuss scenarios where photo-identification may prove particularly effective. Through this review, we therefore aim to encourage the broader use of natural body markings as a non-invasive method in bony fish research, management and conservation
More haste, less speed: the spectroscopy of fast and slow photoproducts in animal cryptochromes
No full textAvian magnetoreception — the ability of some bird species to sense the Earth’s magnetic field to aid with migrational navigation — is the focal point of this thesis. The hypothesis investigated in this work is that of the radical pair mechanism (RPM) in cryptochromes, blue-light photoreceptor proteins found in the retinae of birds. Through magnetic field-dependent mixing between the spin states of a photogenerated radical pair, inducing a change in reaction kinetics and yields, it has been shown in previous works that cryptochromes are suitable for magnetic sensing. Background regarding avian magnetoreception and the radical pair mechanism, and an introduction to the spin interactions and systems of interest discussed throughout this thesis, are provided in Chapter 1.
This thesis presents an investigation of cryptochromes studied by a range of electron paramagnetic resonance (EPR) and UV-visible (UV-vis) spectroscopies, introduced in Chapter 2. Transient EPR (trEPR) and out-of-phase electron spin echo envelope modulation (out-of-phase ESEEM) are continuous wave and pulsed EPR techniques, respectively, used to identify photogenerated spin-correlated radical pairs (SCRPs). trEPR spectroscopy yields spin-polarised EPR spectra, with the lineshape influenced by all interactions of the electron spins with each other, nearby nuclei, and their local environments. Out-of-phase ESEEM reports directly on the inter-electron spin interactions, from which the inter-radical separation can be determined. A third EPR technique, electron nuclear double resonance (ENDOR), is used to probe the hyperfine couplings between electron and nuclear spins in long-lived radicals. This last technique is paired with UV-vis spectroscopy in this work, which, under continuous-illumination conditions, allows a kinetic profiling of long-lived absorbing species.
Chapter 3 presents a spectroscopic investigation of European robin (ErCry4a), chicken (GgCry4a), and common quail (CcCry4a) cryptochromes. Article 1, presented therein, focuses on GgCry4a and probes many facets of the cryptochrome photocycle, with identification of the SCRPs formed (and thus, determination of the electron transfer pathway) being the principal focus for the purpose of this thesis. In this work, the wild-type (WT) protein and three single-point mutants were investigated, in order to understand the significance of the identity of amino acids that are both part of, and close to, the electron transfer chain. Using a combination of out-of-phase ESEEM and trEPR techniques, electron transfer across a tetrad of tryptophan residues — with a flavin adenine dinucleotide (FAD) cofactor acting as the initial electron acceptor — was identified in the case of GgCry4a WT. Formation of an identical [FAD – W369 (W_D)] radical pair was observed in the R317C and E320K mutants, with optical spectroscopy techniques also illustrating a lack of change in the photochemistry between these three species. In contrast, GgCry4a W369F (where the terminal tryptophan residue is replaced with nominally redox-inactive phenylalanine) was shown to undergo electron transfer across a tryptophan triad, with an increased magnetic field effect observable by optical spectroscopy compared to the WT/R317C/E320K samples. Articles 5 and 6, presented in the appendix, discuss similar studies on ErCry4a and CcCry4a, in the context of WT and W369F samples. In both cases, the radical pair identities are again successfully determined using out-of-phase ESEEM and trEPR, forming the basis for the rest of this thesis.
The work on GgCry4a radical pairs is expanded upon in Chapter 4. This chapter, via Article 2, discusses the role of tyrosine and phenylalanine residues in the electron transfer pathways of GgCry4a, through radical pair identification by trEPR and out-of-phase ESEEM in a number of single- and double-point mutated samples. Through further investigation of samples involving W369F and Y319F mutations, a tyrosine-based radical pair was identified in the case of GgCry4a W369F. In addition, extended electron transfer was observed for all W_X F mutations (X = A–D, denoting each position in the tryptophan tetrad), suggesting that phenylalanine may not be a suitable substitution for completely blocking electron transfer.
Using the knowledge accrued in previous chapters, the investigation of cryptochrome photochemistry — specifically, radical pair formation — is extended to proteins from across the animal kingdom (Chapter 5). In addition to the robin, chicken, and quail species discussed in previous chapters, the catalogue of avian species is expanded in Article 3 to include cryptochrome from pigeon, Eurasian blackcap, and Sunda zebra finch. Aside from birds, the radical pairs formed in fruit fly and zebrafish cryptochromes were also identified. In addition to present-day species, this work attempts to retrace the evolutionary pathway, by examining the radical pairs formed in reconstructed ancestral cryptochromes. For the WT samples investigated in this work, near-identical [FAD – W_D] radical pairs were identified in each case, across the animal kingdom and through evolutionary (ancestor) species. An equivalent conservation of [FAD – W_C] radical pairs was also found for W_D F samples, with the possible formation of tyrosine-based radical pairs, as introduced in Chapter 4, discussed further. This work provides an important comparison of the early steps of cryptochrome photochemistry across a wide span of modern and ancient animal species, of varying migratory and magnetosensitive ability.
This thesis concludes with a shift in focus to the long-lived photogenerated species in cryptochromes, that are proposed to be signalling states in the RPM (Chapter 6). In Article 4, 1H ENDOR spectroscopy was used to investigate the flavin radicals that form in a variety of cryptochromes, with clear differences in the ENDOR spectra allowing for direct determination of the flavin protonation state (i.e., FADH• or FAD•−). In this article, the photoreduction of flavin species in avian and ancestral species was also modelled kinetically, using UV-vis spectroscopy of cryptochromes under continuous illumination. The rates and yields of formation of FADH• and FADH− were determined for a collection of WT samples, with a possible trend in photoreduction of FAD compared to species’ migratory ability identified. This chapter also discusses the effect of modifications to the electron transfer chain on the seconds-to-hours photoreduction of GgCry4a, via UV-vis spectroscopy of GgCry4a W_X F mutants. The degree of flavin photoreduction observed in these samples is paired with the extent of electron transfer identified in Chapter 4, thereby connecting the work on short-timescale radical pair formation — key to magnetic sensing — to the long-timescale photochemistry of cryptochromes — where magnetic signalling is proposed to occur
Relationship between personality and sleep: a dual validation study combining empirical and big data-driven approaches
Get PDFObjective: Sleep is a vital component of individual health, and personality traits are key factors influencing it. This study aims to investigate the relationship between personality traits and both modelassessed sleep problems and self-reported sleep quality. Methods: Using deep semantic understanding technology, we developed three deep learning models based on microblogs. Model 1 and Model 2 identified whether a post indicated a sleep problem, while Model 3 assessed the user’s personality traits based on the Five-Factor Model (FFM). We surveyed a dataset comprising 336 active users and then applied the models to a large-scale microblog dataset containing 4,860,000 posts from 15,251 users. Results: Our experimental results revealed that: (1) conscientiousness, agreeableness, and extraversion are associated with better sleep quality, while neuroticism is linked to poorer sleep quality; (2) the relationships between sleep problems and personality traits remained consistent when the model, trained on a small survey dataset with expert annotations, was applied to the large-scale dataset. Conclusions: These findings highlight the potential of using deep learning models to analyze the complex relationship between personality traits and sleep, offering valuable insights for future research and interventions
Large-scale epidemiology of opisthorchiasis in 21 provinces in Thailand based on diagnosis by fecal egg examination and urine antigen assay and analysis of risk factors for infection
Get PDFIntroduction: Infection with the carcinogenic fish-borne trematode Opisthorchis viverrini, known as opisthorchiasis, is a major cause of biliary cancer (cholangiocarcinoma). Despite decades of disease prevention and control in Thailand, the parasite remains endemic. Here we apply a novel antigen assay for mass screening of opisthorchiasis and compare the prevalence against the conventional examination and analyze risk factors associated with current O. viverrini infection. Materials and methods: We conducted a large-scale cross-sectional survey to assess transmission of O. viverrini in the North, Northeast, and Eastern regions of Thailand. We screened randomly selected people (age 15 years and over) in 23 sub-districts, within 21 provinces, with a target sample size of 1,000 per sub-district. Each participant was screened for multiple helminth infection by fecal examination (quantitative formalin-ethyl acetate concentration technique; FECT), and the antigen assay by monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) was applied to urine samples to detect O. viverrini. We collected risk factors for O. viverrini infection using standardized questionnaire surveys. The data were analyzed with regression models which correlated individual-level explanatory variables against i) infection status with O. viverrini and ii) the intensity of infection, as measured by the antigen assay or FECT. Findings: Of the 20,322 individuals enrolled, 19,465 provided urine samples for antigen detection by ELISA and 18,929 provided fecal samples for examination by FECT. The urine antigen assay revealed an overall opisthorchiasis prevalence of 50.3%, a fourfold increase over the 12.2% prevalence detected by FECT. Marked spatial heterogeneity was observed, with antigen‐based prevalence estimates ranging from 22.2% to 71.4% and several localities exceeding 60%. When assessed against a composite reference standard (combined ELISA and FECT), the urine ELISA yielded a diagnostic sensitivity of 91.6%, compared with 21.9% for FECT. We found a positive correlation between fecal egg counts and the concentration of worm antigen in urine across study sites. The ratio between the prevalence of O. viverrini observed by the antigen assay and FECT was high in provinces with a low mean number of O. viverrini eggs, and the ratio approached unity as the mean eggs per gram of stool (EPG) increased. Similar aggregate distribution patterns of fecal egg counts (EPG) and urine antigen concentrations suggest that the urine assay has potential for quantitative diagnostic evaluations. When analyzing individual-level risk factors, we further identified age, sex, occupation, a history of prior treatment with praziquantel, history of O. viverrini examination, and raw fish consumption as predictive of infection with O. viverrini, while a higher education level and certain occupations emerged as protective factors. Conclusions and recommendations: Application of the antigen assay to diagnose O. viverrini infection yielded a four-fold higher prevalence than the fecal egg examination, with the highest difference in low endemicity regions, which suggests that previous surveys may have underestimated the extent of opisthorchiasis in Thailand. Given the ease of urine sample collection, our study highlights the potential for application of the antigen assay as a new tool in the control of opisthorchiasis
Multimodal pragmatic jailbreak on text-to-image models
Get PDFDiffusion models have recently achieved remarkable advancements in terms of image quality and fidelity to textual prompts. Concurrently, the safety of such generative models has become an area of growing concern. This work introduces a novel type of jailbreak, which triggers T2I models to generate the image with visual text, where the image and the text, although considered to be safe in isolation, combine to form unsafe content. To systematically explore this phenomenon, we propose a dataset to evaluate the current diffusion-based text-toimage (T2I) models under such jailbreak. We benchmark nine representative T2I models, including two closed-source commercial models. Experimental results reveal a concerning tendency to produce unsafe content: all tested models suffer from such type of jailbreak, with rates of unsafe generation ranging from around 10% to 70% where DALL·E 3 demonstrates almost the highest unsafety. In real-world scenarios, various filters such as keyword blocklists, customized prompt filters, and NSFW image filters, are commonly employed to mitigate these risks. We evaluate the effectiveness of such filters against our jailbreak and found that, while these filters may be effective for single modality detection, they fail to work against our jailbreak. We also investigate the underlying reason for such jailbreaks, from the perspective of text rendering capability and training data. Our work provides a foundation for further development towards more secure and reliable T2I models
Reachability types, traces and full abstraction
Get PDFReachability types are a recent approach to modelling sharing in higher-order languages, aiming to provide separation guarantees through typability. The contextual equivalence problem in such a setting is exacerbated by the need to consider reachability-related constraints on the allowable interactions. In particular, they might weaken the ability of contexts to observe sequentiality.In this paper, we investigate contextual equivalence for reach-ability types through the lens of operational game semantics. We provide a sound trace model for a language equipped with reachability types, and show how to refine it to a fully abstract one, which captures a natural notion of equivalence based on allowing terms to share functions and locations consistently with the assigned reachability annotations. We also discuss the corresponding problem of contextual approximation, along with an inequational full abstraction result. This is a first attempt at defining a fully abstract semantics for reachability types
Translational neuroimaging for infant pain
Get PDFMany newborns are hospitalised, where they undergo clinically essential, noxious procedures. Exposure to these noxious stimuli is known to have harmful effects on infants in both the short-term and the long-term, and there are analgesic and other non-pharmacological interventions which might mitigate these. Despite this, pain is often undertreated in infants. This is partly because of the difficulty in identifying and measuring pain in this population. Our inability to accurately identify and measure pain in this population makes it difficult to evaluate the effect of interventions, and difficult to identify which hospitalised infants would benefit from them.
Neuroimaging measures of nociception have the advantage that they directly measure the brain. They can avoid many of the external confounding factors which are inherent to other methods, such as those based on physiology or behaviour. One particularly promising neuroimaging method is electroencephalography, which can be used to measure noxious evoked potentials (electroencephalographic signals caused by noxious stimuli). In this thesis I address two limitations of noxious evoked potential measurement; I do so by developing new methods for analysis.
The first topic is artefact and I address this in Chapter 4. Artefact in neuroimaging is measurement noise due to non-neural signals. I develop an automated, reproducible artefact detection algorithm. This algorithm uses machine learning techniques to distinguish between ‘clean’ epochs and those containing artefact. It performs as well as experienced raters in a fraction of the time.
The second topic is clinical utility and I address this in Chapter 5. A measurement for research settings does not necessarily translate well into clinical settings. For best clinical utility it is important for a measurement to be easily interpretable. I explore methods for combining individual neuroimaging and physiological metrics into a single, easily interpretable measure.
The overall intention of this thesis is to improve the EEG analysis methodology used both in neuroimaging research of neonatal pain, and in clinical practice
Dynamic change of calcium-rich compartments during coccolithophore biomineralization
Get PDFCoccolithophores are abundant marine phytoplankton that produce biomineralized calcite scales, called coccoliths, which sequester substantial amounts of carbon and play a substantial role in biogeochemical cycles. However, mechanisms underlying the storage and transport of ions essential for calcification remain unresolved. We used ptychographic x-ray computed tomography under cryogenic conditions to visualize intracellular calcium-rich structures involved in the storage of calcium ions in the coccolithophore species Chrysotila carterae. During calcification, we observed a range of structures, from small electron-dense bodies within larger compartments to denser and distributed globular compartments, before returning to small bodies once scale formation is complete. Nanobeam-scanning x-ray fluorescence measurements further revealed that these electron-dense bodies are rich in phosphorus and calcium (molar ratio of ~4:1). The dynamic nature of structures suggests that these bodies are part of the required cellular calcium ion transport pathways, a fundamental process critical for understanding the response of coccolithophores to climate change
The genome sequence of the Small Dotted Buff moth, <i>Photedes minima</i> Haworth, 1809
Get PDFWe present a genome assembly from a male specimen of Photedes minima (Small Dotted Buff; Arthropoda; Insecta; Lepidoptera; Noctuidae). The genome sequence has a total length of 694.66 megabases. Most of the assembly (99.95%) is scaffolded into 31 chromosomal pseudomolecules, including the Z sex chromosome. The mitochondrial genome has also been assembled, with a length of 15.38 kilobases