Therapeutic commitment for general nurses in dealing with mental health problems of People Living with HIV/AIDS in Blantyre, Malawi

Introduction Therapeutic commitment of general nurses influences their provision of mental health care to clients. It is the general nurses’ predisposition for working therapeutically with clients who have mental health problems (MHPs). In Malawi, general nurses are the majority of health care professionals who care for people living with HIV/AIDS (PLWHA) and they are expected to deal with the mental health problems of these patients. The provision of mental health care to PLWHA is vital because apart from the physical illnesses associated with the virus, these people are also affected by mental health problems. However, most general nurses, feel neither confident nor competent when dealing with the mental health problems of their clients in Malawi. This may negatively influence their therapeutic commitment in dealing with mental health problems of PLWHA. However, therapeutic commitment of general nurses in providing mental health care to PLWHA in Malawi remains unknown. Materials and Methods The study used a quantitative descriptive survey design. a convenient sample comprising of 136 general nurses was used and data was collected using Mental Health Problems Perception Questionnaire. Permission to use the tool in this study was granted by Prof. Lauder. Ethical approval to conduct the study was granted by Ethics Committees at University of KwaZulu Natal and University of Malawi. Data were analysed using Statistical Package for Social Sciences version 15.0. Results The study findings revealed that there is a linear relationship between general nurses’ levels of knowledge and skills and their therapeutic commitment (r=.40, n=136, p<.05) to provide mental health care of PLWHA. Conclusion This study suggests general nurses’ levels of therapeutic commitment in dealing with MHPs of PLWHA vary and their levels of knowledge and skill to deal with MHPs influence their willingness to provide mental health care to PLWHA.

TcT: Tyrolean Complexity Tool

International audience

A perfect day for zebrafish : neuromodulation of sleep in a diurnal vertebrate

Every day, we shift among various states of sleep and arousal to meet the many demands of our bodies and environment. A central puzzle in neurobiology is how the brain controls these behavioral states, which are essential to an animal's well-being and survival. Mammalian models have predominated sleep and arousal research, although in the past decade, invertebrate models have made significant contributions to our understanding of the genetic underpinnings of behavioral states. More recently, the zebrafish (Danio rerio), a diurnal vertebrate, has emerged as a promising model system for sleep and arousal research.

In this thesis, I describe two studies on sleep/arousal pathways that I conducted using zebrafish, and I discuss how the findings can be combined in future projects to advance our understanding of vertebrate sleep/arousal pathways. In the first study, I discovered a neuropeptide that regulates zebrafish sleep and arousal as a result of a large-scale effort to identify molecules that regulate behavioral states. Taking advantage of facile zebrafish genetics, I constructed mutants for the three known receptors of this peptide and identified the one receptor that exclusively mediates the observed behavioral effects. I further show that the peptide exerts its behavioral effects independently of signaling at a key module of a neuroendocrine signaling pathway. This finding contradicts the hypothesis put forth in mammalian systems that the peptide acts through the classical neuroendocrine pathway; our data further generate new testable hypotheses for determining the central nervous system or alternative neuroendocrine pathways involved.

Second, I will present the development of a chemigenetic method to non-invasively manipulate neurons in the behaving zebrafish. I validated this technique by expressing and inducing the chemigenetic tool in a restricted population of sleep-regulating neurons in the zebrafish. As predicted by established models of this vertebrate sleep regulator, chemigenetic activation of these neurons induced hyperactivity, whereas chemigenetic ablation of these neurons induced increased sleep behavior. Given that light is a potent modulator of behavior in zebrafish, our proof-of-principle data provide a springboard for future studies of sleep/arousal and other light-dependent behaviors to interrogate genetically-defined populations of neurons independently of optogenetic tools.

A (in)capacidade estatal de defesa dos direitos humanos : o incidente de deslocamento de competência nº 3 e a violência policial no estado de Goiás

Dissertação (mestrado)—Universidade de Brasília, Centro de Estudos Avançados Multidisciplinares, Programa de Pós-Graduação em Direitos Humanos e Cidadania, 2015.

Essays on internationalization in the context of heterogeneous firms

The significant increase in global trade flows in last decades has been one of the main features of the globalization process that started in the 1950s. In general, the main factors behind this increase were linked to (i) the significant reductions of trade costs and technical barriers; (ii) the improvements in transport infrastructure and telecommunications; (iii) the progress of the international financial system and the increasing legal certainty; and (iv) the development of a corporate culture that promotes the internationalization of firms as a strategic tool in order to survive and to grow. The remarkable increase of trade openness has also been observed in the Spanish economy. In this regard, it is clear that the entry into force of the Treaty of Accession of Spain to the European Economic Community (now the European Union) in 1986 played a main role in this dramatic increase. In addition, and because of the deep depression of domestic demand caused by the global financial and economic crisis that started in 2008, the external trade has become a key driver in the economic recovery of the Spanish economy...

Clinical skills and communication in nursing students

Abstract Background: Communication is a basic tool in nursing, a crucial element of care. The quality of the interactions that take place between the nurse and the user/family influence their satisfaction and security felt with the care received. Objectives: To identify the communication skills and interpersonal relationship of nursing students in health care; identify the sociodemographic and academic variables influencing communication skills and interpersonal relationship of nursing students in health care. Methodology: Quantitative study, cross-sectional, descriptive and correlational. The data collection instrument was a questionnaire with questions concerning the socio-demographic and academic characterization; basic skills of interview and clinical communication in health care; learning of clinical communication skills and range of communication skills and interpersonal relationship. The sample consisted of 374 nursing students from two Portuguese schools. Results: The majority were female (80.5%), in the age group of 18-21 years. The students recognize the importance of clinical communication skills and interpersonal relations in nursing practice (82.4%); agreed on the teaching methods of communicational skills (54.3%). Evaluated their training in the area as good (71.7%). Age, semester and school influenced communication skills and interpersonal relationship of students (p <0.5) Conclusion: The results obtained allow us to state that the education / training of nursing student in the relational context is of fundamental importance in building capacity for competent professional practice.

The epidemiology of foot-and-mouth disease at the wildlife-livestock interface in northern Tanzania

Foot-and-mouth disease (FMD), a disease of cloven hooved animals caused by FMD virus (FMDV), is one of the most economically devastating diseases of livestock worldwide. The global burden of disease is borne largely by livestock-keepers in areas of Africa and Asia where the disease is endemic and where many people rely on livestock for their livelihoods and food-security. Yet, there are many gaps in our knowledge of the drivers of FMDV circulation in these settings. In East Africa, FMD epidemiology is complicated by the circulation of multiple FMDV serotypes (distinct antigenic variants) and by the presence of large populations of susceptible wildlife and domestic livestock. The African buffalo (Syncerus caffer) is the only wildlife species with consistent evidence of high levels of FMDV infection, and East Africa contains the largest population of this species globally. To inform FMD control in this region, key questions relate to heterogeneities in FMD prevalence and impacts in different livestock management systems and to the role of wildlife as a potential source of FMDV for livestock. To develop FMD control strategies and make best use of vaccine control options, serotype-specific patterns of circulation need to be characterised. In this study, the impacts and epidemiology of FMD were investigated across a range of traditional livestock-keeping systems in northern Tanzania, including pastoralist, agro-pastoralist and rural smallholder systems. Data were generated through field studies and laboratory analyses between 2010 and 2015. The study involved analysis of existing household survey data and generated serological data from cross-sectional livestock and buffalo samples and longitudinal cattle samples. Serological analyses included non-structural protein ELISAs, serotype-specific solid-phase competitive ELISAs, with optimisation to detect East African FMDV variants, and virus neutralisation testing. Risk factors for FMDV infection and outbreaks were investigated through analysis of cross-sectional serological data in conjunction with a case-control outbreak analysis. A novel Bayesian modeling approach was developed to infer serotype-specific infection history from serological data, and combined with virus isolation data from FMD outbreaks to characterise temporal and spatial patterns of serotype-specific infection. A high seroprevalence of FMD was detected in both northern Tanzanian livestock (69%, [66.5 - 71.4%] in cattle and 48.5%, [45.7-51.3%] in small ruminants) and in buffalo (80.9%, [74.7-86.1%]). Four different serotypes of FMDV (A, O, SAT1 and SAT2) were isolated from livestock. Up to three outbreaks per year were reported by households and active surveillance highlighted up to four serial outbreaks in the same herds within three years. Agro-pastoral and pastoral livestock keepers reported more frequent FMD outbreaks compared to smallholders. Households in all three management systems reported that FMD outbreaks caused significant impacts on milk production and sales, and on animals’ draught power, hence on crop production, with implications for food security and livelihoods. Risk factor analyses showed that older livestock were more likely to be seropositive for FMD (Odds Ratio [OR] 1.4 [1.4-1.5] per extra year) and that cattle (OR 3.3 [2.7-4.0]) were more likely than sheep and goats to be seropositive. Livestock managed by agro-pastoralists (OR 8.1 [2.8-23.6]) or pastoralists (OR 7.1 [2.9-17.6]) were more likely to be seropositive compared to those managed by smallholders. Larger herds (OR: 1.02 [1.01-1.03] per extra bovine) and those that recently acquired new livestock (OR: 5.57 [1.01 – 30.91]) had increased odds of suffering an FMD outbreak. Measures of potential contact with buffalo or with other FMD susceptible wildlife did not increase the likelihood of FMD in livestock in either the cross-sectional serological analysis or case-control outbreak analysis. The Bayesian model was validated to correctly infer from ELISA data the most recent serotype to infect cattle. Consistent with the lack of risk factors related to wildlife contact, temporal and spatial patterns of exposure to specific FMDV serotypes were not tightly linked in cattle and buffalo. In cattle, four serial waves of different FMDV serotypes that swept through southern Kenyan and northern Tanzanian livestock populations over a four-year period dominated infection patterns. In contrast, only two serotypes (SAT1 and SAT2) dominated in buffalo populations. Key conclusions are that FMD has a substantial impact in traditional livestock systems in East Africa. Wildlife does not currently appear to act as an important source of FMDV for East African livestock, and control efforts in the region should initially focus on livestock management and vaccination strategies. A novel modeling approach greatly facilitated the interpretation of serological data and may be a potent epidemiological tool in the African setting. There was a clear temporal pattern of FMDV antigenic dominance across northern Tanzania and southern Kenya. Longer-term research to investigate whether serotype-specific FMDV sweeps are truly predictable, and to shed light on FMD post-infection immunity in animals exposed to serial FMD infections is warranted.

An investigation into the suitability of time-of-flight mass spectrometry in forensic toxicology

Liquid chromatography coupled with mass spectrometry is one of the most powerful tools in the toxicologist’s arsenal to detect a wide variety of compounds from many different matrices. However, the huge number of potentially abused substances and new substances especially designed as intoxicants poses a problem in a forensic toxicology setting. Most methods are targeted and designed to cover a very specific drug or group of drugs while many other substances remain undetected. High resolution mass spectrometry, more specifically time-of-flight mass spectrometry, represents an extremely powerful tool in analysing a multitude of compounds not only simultaneously but also retroactively. The data obtained through the time-of-flight instrument contains all compounds made available from sample extraction and chromatography, which can be processed at a later time with an improved library to detect previously unrecognised compounds without having to analyse the respective sample again. The aim of this project was to determine the utility and limitations of time-of-flight mass spectrometry as a general and easily expandable screening method. The resolution of time-of-flight mass spectrometry allows for the separation of compounds with the same nominal mass but distinct exact masses without the need to separate them chromatographically. To simulate the wide variety of potentially encountered drugs in such a general screening method, seven drugs (morphine, cocaine, zolpidem, diazepam, amphetamine, MDEA and THC) were chosen to represent this variety in terms of mass, properties and functional groups. Consequently, several liquid-liquid and solid phase extractions were applied to urine samples to determine the most general suitable and unspecific extraction. Chromatography was optimised by investigating the parameters pH, concentration, organic solvent and gradient of the mobile phase to improve data obtained by the time-of-flight instrument. The resulting method was validated as a qualitative confirmation/identification method. Data processing was automated using the software TargetAnalysis, which provides excellent analyte recognition according to retention time, exact mass and isotope pattern. The recognition of isotope patterns allows excellent recognition of analytes even in interference rich mass spectra and proved to be a good positive indicator. Finally, the validated method was applied to samples received from the A& E Department of Glasgow Royal Infirmary in suspected drug abuse cases and samples received from the Scottish Prison Service, which we received from their own prevalence study targeting drugs of abuse in the prison population. The obtained data was processed with a library established in the course of this work.

Celiac disease in children from Madeira island and its prevalence in first degree relatives

Context - It is well recognized that celiac disease is an immune-mediated systemic disorder highly prevalent among relatives of celiac patients. Objectives - The aim of this study is to determine the prevalence of celiac disease in a group of first degree relatives of celiac children, and to access the frequency of human leukocyte antigen HLA-DQ2 and DQ8 in celiac disease patients and their affected relatives. Methods - A survey was conducted of 39 children with celiac disease with follow-up in the Pediatric outpatient’s clinic of Dr. Nélio Mendonça Hospital, in Madeira Island, Portugal. Were invited 110 first degree relatives to undergo serological screen for celiac disease with IgA antibody to human recombinant tissue transglutaminase (IgA-TGG) quantification. In all seropositive relatives, small intestinal biopsy and HLA typing was recommended. Results - HLA- typing was performed in 38 celiac patients, 28/74% DQ2 positive, 1/2% DQ8 positive and 9/24% incomplete DQ2. Positive IgA-TGG was found in five out of the 95 relatives, and CD was diagnosed in three of them. Three relatives had the presence of HLA-DQ2, two were DQ2 incomplete (DQB1*02). Conclusion - The prevalence of celiac disease among first degree celiac patients´ relatives was 3.1%, 4.5 times higher than the general Portuguese population (0,7%) witch reinforces the need of extensive diagnostic screening in this specific group. HLA-DQ2 typing may be a tool in the diagnostic approach.

Incidencia de síndrome de abstinencia secundario a opioides y/o benzodiacepinas en dos unidades de cuidados intensivos pediátricos

• Introducción: El síndrome de abstinencia (SA) es el conjunto de síntomas y signos que se producen al suspender bruscamente la administración de un fármaco una vez se haya establecido dependencia física. • Objetivos: Caracterizar los pacientes que presentan SA secundario a opiodes (OP) y/o benzodiacepinas(BZ) durante la hospitalización en las unidades de cuidados intensivos pediátricos de la Clínica Infantil Colsubsidio (CIC) y Hospital del Niño de Panamá (HDN) del 1 de abril al 30 de septiembre del 2016. • Materiales y métodos: se realizó un estudio descriptivo, longitudinal, prospectivo. Incluimos 189 pacientes en la CIC y 144 pacientes en el HDN. Se utilizó la escala SOPHIA para el diagnóstico de SA, las escalas COMFORT para evaluar la sedación en pacientes ventilados no relajados y la escala FLACC para evaluar la analgesia. Se utilizó software StataV12® para el análisis estadístico. • Resultados: se reportó una incidencia global de SA de 6.1/100 días personas. La incidencia acumulada de SA fue de 56.08% y 29.86% para la CIC y el HDN respectivamente. En la CIC el 69.81% de los pacientes que requirieron infusión de OP y BZ desarrollaron SA. Se reportó una dosis acumulada de fentanyl de 530.34 ± 276.49 mcg/kg. Con respecto al HDN, de los pacientes que recibieron opioides y benzodiacepinas el 53.49 % desarrollaron SA. • Conclusión: El SA secundario a opioides y/o benzodiacepinas es frecuente en nuestras unidades con una incidencia variable, es mayor la presentación del SA al usar ambos fármacos, mayores dosis acumuladas y más días de infusión continua.

The use of motivational interviews by nurses to promote health behaviors in adolescents: developing a search strategy for this review

Introduction: The developmental changes during adolescence may affect subsequent risk for diseases and health-related behaviors. Motivational Interview (MI) may be taken as an essential tool in the provision of nursing care to adolescents, being itself a workspace with possible therapeutic effects. At this context, it is important to examine and map the use of MI by nurses in their clinical practice with adolescents to promote health behaviors. Objectives: A scoping review has been undertaking to find out what is the current extent of the use of nurse-led MI; which adolescents were included; in which contexts nurses use MI; which MI techniques/strategies are used and what outcomes have been reported. The first task was to develop a search strategy to identify relevant studies for this review. It is described here the experience in constructing the search strategy review. Methodology: This scoping review will be informed by JBI methodology. An initial search of MEDLINE and CINAHL was undertaken. An analysis of the text words contained in the title and abstract, and of the index terms used to describe the searched articles were retrieved and these were then used to construct a search strategy for use in Medline and Cinahl. Results: Analysis of the text words and the index terms generated 19 keywords: It was identified 5 synonyms for "Adolescents", 12 for "MI" and 2 for "nurse". A new research formula was designed using the text words identified. Adolescen*[Title/Abstract]) OR Younger*[Title/Abstract]) OR Youth*[Title/Abstract]) OR Teen*[Title/Abstract]) OR Adolescent[MeSH Terms])) AND (((((((((((("Motivational interview"[Title/Abstract]) OR "Motivational intervention"[Title/Abstract]) OR "Motivational interviews"[Title/Abstract]) OR "Motivational interventions"[Title/Abstract]) OR "motivational interviewing"[Title/Abstract]) OR "motivational counseling"[Title/Abstract]) OR "motivational support"[Title/Abstract]) OR "Motivational enhancement"[Title/Abstract]) OR "Brief intervention"[Title/Abstract]) OR "Brief interventions"[Title/Abstract]) OR Motivational Interviewing[MeSH Terms]) OR Directive Counseling[MeSH Terms])) AND ((nurs*[Text Word]) OR Nurses[MeSH Terms]). Limiters - Language: English, Portuguese, Spanish. In MEDLINE this research formula generated 125 results. Other 16 databases referenced at the protocol will be searched to identify additional studies. Articles identified from the final search will be assessed for relevance to the review, based on information provided in the title and abstract. The full article will be retrieved for all studies that meet the inclusion criteria of the review. Conclusions: It was presented here the initial results of this search. Next steps of this study will be to develop and refine the search strategy for use in other databases. It is expected that findings from this Scoping Review provide needed information to nurses related to the use of MI to promote health behaviors in adolescents and inform opportunities for future development in nursing practice.

Restricting the flexibility in DEA models

DEA models have been applied as the benchmarking tool in operations management to empirically account operational and productive efficiency. The wide flexibility in assigning the weights in DEA approach can result on indicators of efficiency who do not take account the relative importance of some inputs. In order to overcome this limitation, in this research we apply the DEA model under restricted weight specification. This model is applied to Spanish hotel companies in order to measure operational efficiency. The restricted weight specification enables us to decrease the influence of assigning unrealistic weights in some units and improve the efficiency estimation and to increase the discriminating potential of the conventional DEA model.

Mapping spatial and temporal potassium balances in Brazilian soils of south-west Goias.

Introduction: Brazil, is one of the main agricultural producers in the world ranking 1st in the production of sugarcane, coffee and oranges. It is also 2nd as world producer of soybeans and a leader in the harvested yields of many other crops. The annual consumption of mineral fertilizers exceeds 20 million mt, 30% of which corresponds to potash fertilizers (ANDA, 2006). From this statistic it may be supposed that fertilizer application in Brazil is rather high, compared with many other countries. However, even if it is assumed that only one fourth of this enormous 8.5 million km2 territory is used for agriculture, average levels of fertilizer application per hectare of arable land are not high enough for sustainable production. One of the major constraints is the relatively low natural fertility status of the soils which contain excessive Fe and Al oxides. Agriculture is also often practised on sandy soils so that the heavy rainfall causes large losses of nutrients through leaching. In general, nutrient removal by crops such as sugarcane and tropical fruits is much more than the average nutrient application via fertilization, especially in regions with a long history of agricultural production. In the recently developed areas, especially in the Cerrado (Brazilian savanna) where agriculture has expanded since 1980, soils are even poorer than in the "old" agricultural regions, and high costs of mineral fertilizers have become a significant input factor in determining soybean, maize and cotton planting. The consumption of mineral fertilizers throughout Brazil is very uneven. According to the 1995/96 Agricultural Census, only in eight of the total of 26 Brazilian states, were 50 per cent or more of the farms treated "systematically" with mineral fertilizers; in many states it was less than 25 per cent, and in five states even less than 12 per cent (Brazilian Institute for Geography and Statistics; Censo Agropecuario1995/96, Instituto Brazileiro de Geografia e Estadistica; IBGE, www.ibge.gov.br). The geographical application distribution pattern of mineral fertilizers may be considered as an important field of research. Understanding geographical disparities in fertilization level requires a complex approach. This includes evaluation of the availability of nutrients in the soil (and related soil properties e.g. CEC and texture), the input of nutrients with fertilizer application, and the removal of nutrients by harvested yields. When all these data are compiled, it is possible to evaluate the balance of particular nutrients for certain areas, and make conclusions as to where agricultural practices should be optimized. This kind of research is somewhat complicated, because it relies on completely different sources of data, usually from incomparable data sources, e.g. soil characteristics attributed to soil type areas, in contrast to yields by administrative regions, or farms. A priority tool in this case is the Geographical Information System (GIS), which enables attribution of data from different fields to the same territorial units, and makes possible integration of these data in an "inputoutput" model, where "input" is the natural availability of a nutrient in the soil plus fertilization, and "output" export of the same nutrient with the removed harvested yield.

Impact of Protein Induced by Vitamin K Absence (PIVKA-II) in diagnosis and monitoring of patients with hepatocellular carcinoma

Background and Aims: Hepatocellular carcinoma (HCC) represents the second leading cause of cancer deaths worldwide. Protein induced by vitamin K absence (PIVKA-II) has been proposed as potential screening biomarker for HCC.This study has been designed to evaluate the role of PIVKA-II as diagnostic HCC marker, through the comparison between PIVKA-II and alpha-fetoprotein (AFP) serum levels on HCC patients and the two control groupsof patients with liver disease and without HCC. Methods: In an Italian prospective cohort, PIVKA-II levels were assessed on serum samplesby an automated chemiluminescent immunoassay (Abbott ARCHITECT). The study population included 65 patients with HCC (both “de novo” and recurrent), 111 with liver cirrhosis (LC) and 111 with chronic hepatitis C (CHC). Results: PIVKA-II levels were increased in patients with HCC (median 63.75, range: 12-2675 mAU/mL) compared to LC (median value: 30.95, range: 11.70–1251mAU / mL, Mann Whitney test p < 0.0001) and CHC (median value: 24.89, range: 12.98-67.68mAU / mL, p < 0.0001).The area under curve (AUC) for PIVKA-II was 0.817 (95% Confidence Interval(CI), 0.752-0.881). At the optimal threshold of 37 mAU / mL, identified by the Youden Index, the sensitivity and specificity were 79% and 76%, respectively. PIVKA-II was a better biomarker than AFP for the diagnosis of HCC, since the AUC for AFP was 0.670 (95% CI 0.585-0.754, p<0.0001) and at the best cutoff of 16.4 ng / mL AFP yielded 98% specificity but only 34% sensitivity. Conclusions:These initial data suggest the potential utility of this tool in the diagnosis of HCC.PIVKA-II alone or in combination may help to an early diagnosis of HCC and a significant optimization of patient management.

Correlations between cardiac magnetic resonance and histologic findings in Anderson Fabry disease

ABSTRACT Background Cardiac magnetic resonance (CMR) has been shown as promising diagnostic tool in Anderson-Fabry disease (AFD) cardiomyopathy due to its ability to detect fat deposits through lower native T1 values. However no histological validation has been provided to date. Objectives To correlate CMR and histologic findings in different cardiac stages of AFD focusing on T1 mapping. Methods Fifteen AFD patients (49 years [IQR 39-63], 60% females) undergoing CMR (cines, native T1 and T2 mapping, LGE and post-contrast T1 imaging) and endomyocardial biopsy (EMB, n=11) or septal myectomy (n=4), were retrospectively evaluated. Tissue specimens were analyzed with light/electron microscopy and vacuolization amount calculated as percentages of vacuolated myocytes and vacuolated myocyte area (%VMA) through a quantitative histomorphometric color-based analysis. Results In patients without increased indexed left ventricular mass (LVMi) at CMR (67%), T1 fell as %VMA increased (r= -0.883; p<0.001), whereas no clear relationship was evident once increased LVMi occurred (r= -0.501; p=0.389). At least 45% of vacuolized myocytes and 10% of VMA were needed for low T1 to occur. %VMA positively correlate with maximal wall thickness (MWT, r=0.860, p<0.0001) and LVMi (r= 0.762; p<0.001). Increased MWT and LVMi were present with at least 45% and 80% of vacuolated myocytes, respectively, and 18% and 22% of VMA. Conclusions This study demonstrated an inverse correlation between native T1 and the vacuolization amount in patients without increased LVMi at CMR, providing a histological validation of low native T1 in AFD. Importantly, a significant vacuolization burden was needed before low T1 and left ventricle hypertrophy occurred.