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1.
J Forensic Leg Med ; 103: 102683, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38669956

ABSTRACT

BACKGROUND: Sexual assault (SA) poses a threat to all areas of contemporary society. Although older individuals represent a vulnerable demographic, a considerable gap exists in the literature regarding the context in which older individuals experience SA. This study aims to provide a comprehensive description of older individuals' attendances at the Sexual Assault Treatment Unit (SATU) network in the Republic of Ireland. METHODS: A 7-year national cross-sectional study was performed to analyse the attendances of older people (≥65 years old) to the SATU network, and to compare them with younger attendances (<65 years old), with a more in-depth subset analysis of Dublin SATU attendances. RESULTS: During the study period, there were 6478 attendances to the SATU network, of which 0.93 % (n = 60) were older people. These included 59 females and 1 male, with the average age of 76.05 years ± 8.16. Forensic examinations were performed in 81.7 %, with the majority seeking assistance within 7 days (80 %). Comparison of older (≥65 years) and younger (<65 years) attendees revealed older individuals were more uncertain whether a sexual assault had occurred (35.5 % vs. 14.4 %, p < 0.001) but more likely to report the incident to the police (78.3 % vs. 64.3 %, p = 0.02). Assault by a person in authority was significantly more common in older age groups (11.7 % vs. 1.8 %, p < 0.001). Older individuals were significantly more likely to be assaulted in their own home (33.3 % vs. 21.5 p < 0.03) or in 'other-indoors' settings (e.g. nursing home/hospital) (43.3 % vs. 23.4 % p < 0.001). They were less likely to be assaulted in the assailant's home (5.0 % vs. 22.9 %, p < 0.001) or outdoors (5.0 % vs. 19.7 %, p = 0.004). In our subset analysis of 19 cases, 73.7 % occurred in healthcare facilities, 63.2 % had dementia, and 42.1 % were care dependent. Genital injuries were present in 44.4 % of patients and extra-genital injuries in 22.2 %. CONCLUSION: Unique patterns are evident in sexual assault experienced by older people, underscoring the necessity for tailored interventions and effective support systems for reporting and addressing this vulnerable demographic. This is especially crucial in healthcare environments, where a notable proportion of cases occur, frequently involving individuals with dementia and requiring care assistance.


Subject(s)
Crime Victims , Sex Offenses , Humans , Female , Ireland/epidemiology , Male , Aged , Cross-Sectional Studies , Sex Offenses/statistics & numerical data , Middle Aged , Crime Victims/statistics & numerical data , Aged, 80 and over , Adult , Age Distribution , Elder Abuse/statistics & numerical data
2.
PLoS One ; 19(4): e0300630, 2024.
Article in English | MEDLINE | ID: mdl-38578754

ABSTRACT

The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development. From this perspective our observation of media-conditional lethal metabolism in respiratory mutants of the opportunistic fungal pathogen Candida albicans was of interest. C. albicans mutants defective in NADH:ubiquinone oxidoreductase (Complex I of the electron transport chain) exhibit normal growth in synthetic complete medium. In YPD medium, however, the mutants grow normally until early stationary phase whereupon a dramatic loss of viability occurs. Upwards of 90% of cells die over the subsequent four to six hours with a loss of membrane integrity. The extent of cell death was proportional to the amount of BactoPeptone, and to a lesser extent, the amount of yeast extract. YPD medium conditioned by growth of the mutant was toxic to wild-type cells indicating mutant metabolism established a toxic milieu in the media. Conditioned media contained a volatile component that contributed to toxicity, but only in the presence of a component of BactoPeptone. Fractionation experiments revealed purine nucleosides or bases as the synergistic component. GC-mass spectrometry analysis revealed acetal (1,1-diethoxyethane) as the active volatile. This previously unreported and lethal synergistic interaction of acetal and purines suggests a hitherto unrecognized toxic metabolism potentially exploitable in the search for antifungal targets.


Subject(s)
Antifungal Agents , Candida albicans , Animals , Humans , Candida albicans/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Acetals/metabolism , Electron Transport Complex I/metabolism
3.
Nat Commun ; 15(1): 1866, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38424080

ABSTRACT

Fluorinated organic compounds are frequently used across the chemical and life sciences. Although a large, structurally diverse pool of alkyl fluorides is nowadays available, synthetic applications trail behind the widely accepted utility of other halides. We envisioned that C(sp2)-C(sp3) cross-coupling reactions of alkyl fluorides with fluorophilic organozinc compounds should be possible through a heterolytic mechanism that involves short-lived ion pairs and uses the stability of the Zn-F bond as the thermodynamic driving force. This would be mechanistically different from previously reported radical reactions and overcome long-standing limitations of organometallic cross-coupling methodology, including competing ß-hydride elimination, homodimerization and hydrodefluorination. Here, we show a practical Csp3-F bond functionalization method that expands the currently restricted synthetic space of unactivated primary, secondary and tertiary C(sp3)-F bonds but also uses benzylic, propargylic and acyl fluorides. Many functional groups and sterically demanding substrates are tolerated, which allows practical carbon-carbon bond formation and late-stage functionalization.

4.
Int J Legal Med ; 138(3): 997-1010, 2024 May.
Article in English | MEDLINE | ID: mdl-37971512

ABSTRACT

BACKGROUND: Sexual violence is a prevalent issue in contemporary society requiring a robust forensic healthcare response. It is critically important that forensic examiners put clinical examination findings into an appropriate evidence-based context. The presence of genital injuries has been shown to increase the likelihood of successful criminal prosecution and report the crime. However, the reported rates of genital injury vary widely in published studies. AIMS AND OBJECTIVES: We aim to critically evaluate and synthesize existing literature on the prevalence of genital injuries in post-pubertal females, examined following sexual violence, with a view to describing the prevalence and characteristics of genital injuries as well as the range of forensic practices employed. METHODS: Three online databases (PubMed, Embase, and Scopus) were systematically searched with key terms. RESULTS: Of the 1224 studies screened, 141 full-text publications met the inclusion criteria. Reported injury prevalence rates varied widely. Details pertaining to forensic examinations included in each study, such as grade of the examiner, type of examination, location of examination, and time interval from assault to examination also varied widely. Injury prevalence was highest in studies where enhanced visualization techniques were utilized. CONCLUSIONS: This systematic review demonstrates that there is no universally agreed standard for documenting genital injuries in cases of sexual violence and highlights the need for standardized approaches and guidelines for assessing, documenting, and reporting these injuries. The review provides robust evidence to support a call for establishing consistent context, terminology, classification systems, and data collection methods to improve the comparability and reliability of future research findings.


Subject(s)
Crime Victims , Rape , Sex Offenses , Female , Humans , Prevalence , Reproducibility of Results , Genitalia/injuries
5.
J Matern Fetal Neonatal Med ; 36(2): 2225115, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37322830

ABSTRACT

BACKGROUND: Neonatal leukemoid reaction is associated with higher risk of mortality, chronic lung disease and has been associated with chorioamnionitis. Literature on extremely low birth weight infants with leukemoid reaction is limited. OBJECTIVES: The aim of our study was to characterize the maternal and placental factors associated with neonatal leukemoid reaction and to describe outcomes of these ELBW infants. Our objective was to assess if there were maternal factors that would assist the decision-making process regarding the delivery of preterm infants at risk of chorioamnionitis and the sequelae of this inflammatory process. METHODS: This was a retrospective case-control study performed in a single, tertiary Maternity Hospital in Dublin. Two matched controls were identified for each case based on gestation and year of birth and data was collected on both the infants and their mothers. RESULTS: 7 extremely preterm neonates were identified as having a leukemoid reaction, defined as a total white cell count of >50,000 or in the first seven days of life. Baseline characteristics between the groups were similar. The median gestational age in the cases group was 24 + 4 weeks and in the control group was 24 + 1. The mean birthweight was 650 g in the cases group vs. 655 g in the control group. There was a higher percentage of males in the control group, 42.9% vs 28.6% in the cases. The preterm infants with leukemoid reaction had a longer duration of ventilation with a median of 18 days (7.5-23.5 days) compared to 6.5 days (2.8-24.5 days) in the control group. More infants in the leukemoid reaction group required inotropes for hypotension in the first 72 h after delivery (42.9% vs 7.1% in the controls, p value .169). Death or Bronchopulmonary dysplasia (BPD) occurred in 85.7% of the cases identified with a leukemoid reaction vs 71.4% of the controls matched. Median maternal CRP was higher in cases prior to delivery vs the controls (66 vs 18.1 mg/L, p-value = .2151). There was histological evidence of maternal inflammatory response in all cases with fetal inflammatory response in 71% of cases. CONCLUSIONS: Leukemoid reaction in ELBW infants with evidence of maternal and fetal inflammatory response syndrome on placental histology is associated with a longer duration of initial ventilation, increased need for inotropes in the first 72 h after birth, higher rates of death, and BPD. Prospective studies are required to identify potential biomarkers such as proinflammatory cytokines, IL-6, which might aid the decision-making process in delivery.


Subject(s)
Bronchopulmonary Dysplasia , Chorioamnionitis , Leukemoid Reaction , Infant , Male , Infant, Newborn , Humans , Female , Pregnancy , Infant, Extremely Premature , Retrospective Studies , Leukemoid Reaction/epidemiology , Case-Control Studies , Chorioamnionitis/epidemiology , Intensive Care Units, Neonatal , Placenta , Gestational Age
6.
Eur J Obstet Gynecol Reprod Biol ; 285: 159-163, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37120912

ABSTRACT

INTRODUCTION: Unsuccessful operative vaginal delivery (OVD) is associated with high rates of materno-fetal morbidity. We aimed to examine institutional rates of unsuccessful OVDs (uOVD) and compare them with successful OVD (sOVD) in order to identify factors to aid patient selection and education. METHODS: A 6-month retrospective cohort study was performed on all unsuccessful and successful OVDs in a tertiary level maternity hospital in the Republic of Ireland. Maternal demographics and obstetric factors were assessed to evaluate potential underlying risk factors for unsuccessful operative vaginal delivery versus successful vaginal delivery. RESULTS: There were 4,191 births during the study period with an OVD rate of 14.2% (n = 595) with 28 (4.7% of OVDs) being unsuccessful. Unsuccessful OVD were predominately nulliparous (25; 89.2%) with a mean maternal age of 30.1 years (range 20-42), with more than half (n = 15, 53.5%) being induced. The most common indication for induction was prolonged rupture of membranes (PROM) (n = 7, 25%) which was significantly different from the successful OVD group. A senior obstetrician was significantly more likely to be the primary operator in uOVD when compared to sOVD. (82.1 % V 54.1% p < 0.01). The majority of unsuccessful OVD were vacuum deliveries (n = 17; 60.7%), with a significantly higher mean birthweight when compared to successful OVD (3.695 kg V 3.483 kg; p < 0.01). Following an unsuccessful OVD, women were more likely to have a postpartum haemorrhage (64.2 % V 31.5% p < 0.01) and their infant was more likely to require admission to the neonatal intensive care unit (NICU) (32.1 % V 5.8% p < 0.01) when compared with successful OVD. CONCLUSION: Risk factors for unsuccessful OVD were higher birth weight and induction of labour. There was a higher incidence of postpartum haemorrhage and NICU admission when compared with successful OVD.


Subject(s)
Fetal Membranes, Premature Rupture , Postpartum Hemorrhage , Infant, Newborn , Female , Pregnancy , Humans , Young Adult , Adult , Postpartum Hemorrhage/epidemiology , Postpartum Hemorrhage/etiology , Retrospective Studies , Delivery, Obstetric/adverse effects , Vacuum Extraction, Obstetrical/adverse effects , Fetal Membranes, Premature Rupture/etiology
8.
Org Lett ; 24(47): 8719-8723, 2022 Dec 02.
Article in English | MEDLINE | ID: mdl-36394939

ABSTRACT

Cross-coupling of alkyl fluorides and organocuprates is accomplished via aluminum halide mediated C-F bond activation and subsequent Csp2-Csp3 and Csp3-Csp3 bond formation. Relatively mild conditions allow for smooth activation of notoriously challenging primary and secondary alkyl fluorides while competing alkyl chain rearrangement, HF elimination, and homocoupling reactions are effectively controlled. The utility and functional group tolerance are demonstrated with 23 examples and a variety of coupling products obtained in up to 88% yield.

9.
Int J Med Inform ; 168: 104899, 2022 12.
Article in English | MEDLINE | ID: mdl-36335797

ABSTRACT

BACKGROUND: Virtual reality learning environments (VRLE) have the potential to transform the delivery of teaching in obstetrics. Medical students often find it difficult to conceptualize fetal lie and presentation. METHODOLOGY: We conducted a single-centre randomized control trial of medical students using VRLE (n = 35) to depict fetal lie and presentation, compared with a control group (n = 34) using traditional 2-dimensional images. The VRLE, delivered using a mounted display headset, created an immersive experience exploring fetal lie and presentation. Clinical examination skills were then assessed using an obstetric abdominal model. The primary outcome was knowledge, as assessed by determination of fetal lie and presentation on an obstetric model. Secondary outcomes were time taken to successfully complete the task, and the student experience. RESULTS: There was a non-significant trend towards improved knowledge outcomes using the VRLE compared to traditional methods with 70 % (n = 23) in the VRLE group determining the correct fetal lie and presentation compared with 56 % (n = 19) in the control group (OR.551 CI 0.202-1.504, p = 0.242). Students in the intervention group more efficiently completed the task (45 s ± 12.95 vs 38 s ± 10.83 CI 1.701,13.367p = 0.012) and better enjoyed the virtual learning experience with student confidence and satisfaction scores significantly higher (p = 0.02). CONCLUSION: It is feasible to use VRLE to teach medical students clinical skills such as fetal lie and presentation, enhancing the learning experience in both student satisfaction and confidence, with positive trends towards improved knowledge outcomes demonstrated.


Subject(s)
Education, Medical , Students, Medical , Virtual Reality , Humans , Learning , Clinical Competence , Teaching
10.
Ulster Med J ; 91(2): 117-118, 2022 05.
Article in English | MEDLINE | ID: mdl-35722214
12.
Clin Exp Dermatol ; 47(4): 755-757, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34798687

ABSTRACT

Morphoea is a spectrum of disorders characterized by inflammation and sclerosis of the skin and potentially underlying tissues. There are no specific licensed treatments for morphoea and prospective studies on commonly used therapies are lacking. We describe a case of progressive, recalcitrant pansclerotic morphoea with a rapid response to abatacept.


Subject(s)
Scleroderma, Localized , Abatacept/therapeutic use , Humans , Prospective Studies , Scleroderma, Localized/drug therapy , Skin
13.
Evolution ; 75(12): 3026-3036, 2021 12.
Article in English | MEDLINE | ID: mdl-34626427

ABSTRACT

Communal displays such as leks and choruses are puzzling phenomena, as it is not obvious why signalers or choosers should aggregate. It has been hypothesized that signalers in leks enjoy higher per-capita reproductive success because choosers prefer to sample among dense configurations ("clusters") that are easier to compare. Although female preferences as well as the signal features of attractive males are well characterized in many chorusing species, we know little about how mate sampling is influenced by the spatial dynamics within communal displays. Here, we ask how female Eastern Gray Treefrogs (Hyla versicolor) respond to isolated and clustered call stimuli in a simple one versus three playback design. We explored (i) whether females exhibit a general preference for call clusters, (ii) whether spatial preference is robust to call-feature preference, and (iii) how this affects the relative success of attractive and unattractive males in different spatial combinations. We found generalized spatial discrimination against lone callers but did observe fine-scale assessment of call features within clusters. The prominence of the spatial preference impacts the attractiveness of males, conferring particular advantage to attractive callers within clusters, while reducing attractiveness of isolated males regardless of their acoustic features. Our findings indicate that female frogs navigate complex choruses by initially orientating toward clusters of calling males, and then assess call features within them. This study provides novel insight into the mate choice heuristics involved in animal choruses.


Subject(s)
Anura , Vocalization, Animal , Acoustics , Animals , Female , Male
14.
Ulster Med J ; 90(2): 70-76, 2021 May.
Article in English | MEDLINE | ID: mdl-34276083

ABSTRACT

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.


Subject(s)
Dermatitis, Atopic , Eczema , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Child , Dermatitis, Atopic/drug therapy , Double-Blind Method , Health Services Accessibility , Humans , Injections, Subcutaneous , Retrospective Studies , Severity of Illness Index , Treatment Outcome , United Kingdom
16.
Clin Exp Dermatol ; 46(1): 147-152, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32790078

ABSTRACT

This study summarizes the use, since its inception, of the Cutaneous Lupus Disease Area and Severity Index (CLASI) as an outcome measure in clinical studies. We systematically searched the MEDLINE, PubMed, EMBASE and Cochrane databases for papers including the term 'cutaneous lupus disease area and severity index' and its abbreviations up to August 2017, identifying 205 abstracts. Following shortlisting, two independent physicians critically reviewed 71 papers for data extraction. We found that a limited number of high-quality studies used the CLASI scoring as an outcome measure. We concluded that further validation is necessary to identify the effectiveness of the CLASI in the assessment of cutaneous lupus erythematosus subtypes. The use of standardized core patient- and physician-reported outcome measures may reduce heterogeneity and allow comparisons between patients enrolled in clinical trials. This would improve the relevance within clinical practice, where the use of CLASI is currently limited.


Subject(s)
Lupus Erythematosus, Cutaneous , Outcome Assessment, Health Care/methods , Severity of Illness Index , Clinical Trials as Topic , Humans , Treatment Outcome
19.
Cognition ; 182: 127-139, 2019 01.
Article in English | MEDLINE | ID: mdl-30243037

ABSTRACT

The thoughts and feelings people have about pain (referred to as 'pain expectations') are known to alter the perception of pain. However little is known about the cognitive processes that underpin pain expectations, or what drives the differing effect that pain expectations have between individuals. This paper details the testing of a model of pain perception which formalises the response to pain in terms of a Bayesian prior-to-posterior updating process. Using data acquired from a short and deception-free predictive cue task, it was found that this Bayesian model predicted ratings of pain better than other, simpler models. At the group level, the results confirmed two core predictions of predictive coding; that expectation alters perception, and that increased uncertainty in the expectation reduces its impact on perception. The addition of parameters relating to trait differences in pain expectation improved the fit of the model, suggesting that such traits play a significant role in perception above and beyond the influence of expectations triggered by predictive cues. When the model parameters were allowed to vary by participant, the model's fit improved further. This final model produced a characterisation of each individual's sensitivity to pain expectations. This model is relevant for the understanding of the cognitive basis of pain expectations and could potentially act as a useful tool for guiding patient stratification and clinical experimentation.


Subject(s)
Anticipation, Psychological/physiology , Individuality , Models, Psychological , Pain Perception/physiology , Uncertainty , Adult , Aged , Bayes Theorem , Cues , Female , Humans , Male , Young Adult
20.
QJM ; 111(12): 839-843, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-29088421

ABSTRACT

Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus, characterized by progressive dsypnoea, reduced lung volumes and associated restrictive lung physiology. Here, we provide two previously unreported cases, and review the available literature on the pathophysiology, clinical features and management of SLS. Effective treatment can prevent further deterioration or lead to improvement in abnormal lung function. A heightened awareness of SLS and its management is therefore required to prevent disease progression and increased morbidity.


Subject(s)
Lung Diseases/etiology , Lupus Erythematosus, Systemic/complications , Adult , Female , Humans , Lung Diseases/pathology , Lupus Erythematosus, Systemic/pathology , Male , Syndrome
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