207 research outputs found
Eco-evolutionary feedback in fish–zooplankton communities on the Scottish island of North Uist
No full text‘Eco-evolutionary feedbacks’ occur when evolution of organismal traits causes environmental change that drives further evolution. Predator and prey interactions provide good examples of eco-evolutionary feedbacks. \ud
Here I examine the potential for eco-evolutionary feedbacks between three-spined sticklebacks (Gasterosteus aculeatus, hereafter ‘stickleback’) and their zooplankton prey in lochs (lakes) on the Scottish island of North Uist. Many lochs on the island were colonised by sticklebacks after the last glaciation, approximately 10,000-15,000 years ago. Previous work has shown that sticklebacks in different lochs have diverged greatly from each other in response to local environments. On the other hand, apart from several very old studies on the occurrence of some zooplankton species, there have been no previous in depth studies on the population dynamics of zooplankton on North Uist. \ud
I investigated first the diversity and abundance of zooplankton groups and the most common species across all North Uist lochs. Thirty-nine species were classified from three main groups (Rotifera, Cladocera and Copepoda). Species abundance in the presence of fish was relatively more even, while the abundance of zooplankton groups was not generally related to fish presence except for Cladocera in a subset of locations. The effects of predation on the life-history of zooplankton were also examined by comparing reproductive traits of the dominant cladoceran species (Bosmina and Daphnia) in lochs with and without fish. \ud
Cladocerans in lochs with fish have more rapid reproductive cycles and higher fecundity parameters, probably in response to the increased threat of predation. These effects remain evident in Bosmina after they have been raised through three generations in the laboratory, supporting the hypothesis that they have a genetic basis and are not a plastic response to predator presence. Life-history variables of cladocerans were also related to abiotic and biotic variation among lochs, including depth, pH, chlorophyll levels and the concentration of alkaline metals. \ud
I also demonstrate that stickleback have diversified greatly among lochs in functional trophic traits that determine the efficiency of feeding on different types of prey, which could affect total primary production and the structure of prey communities. Ancestral stickleback populations have adapted according to the type of habitat colonised. Fish feed on benthic prey in shallow lochs, which requires greater effort for successful foraging than that required by fish that feed on planktonic prey. I found that variation in stickleback trophic traits was related to both abiotic and biotic variation among lochs, including loch depth and the mean contributions of planktonic and benthic prey to diet.\ud
The results presented in this thesis suggest the possibility of eco-evolutionary feedbacks in these simple ecosystems on North Uist based on the significant responses in fish and zooplankton communities. The thesis also provides a basis for further studies on fish-zooplankton interactions on North Uist and contributes to the wider body of knowledge concerning the relevance of natural variation in shaping the foraging mechanisms of animals
Eco-evolutionary feedback in fish–zooplankton communities on the Scottish island of North Uist
No full text‘Eco-evolutionary feedbacks’ occur when evolution of organismal traits causes environmental change that drives further evolution. Predator and prey interactions provide good examples of eco-evolutionary feedbacks.
Here I examine the potential for eco-evolutionary feedbacks between three-spined sticklebacks (Gasterosteus aculeatus, hereafter ‘stickleback’) and their zooplankton prey in lochs (lakes) on the Scottish island of North Uist. Many lochs on the island were colonised by sticklebacks after the last glaciation, approximately 10,000-15,000 years ago. Previous work has shown that sticklebacks in different lochs have diverged greatly from each other in response to local environments. On the other hand, apart from several very old studies on the occurrence of some zooplankton species, there have been no previous in depth studies on the population dynamics of zooplankton on North Uist.
I investigated first the diversity and abundance of zooplankton groups and the most common species across all North Uist lochs. Thirty-nine species were classified from three main groups (Rotifera, Cladocera and Copepoda). Species abundance in the presence of fish was relatively more even, while the abundance of zooplankton groups was not generally related to fish presence except for Cladocera in a subset of locations. The effects of predation on the life-history of zooplankton were also examined by comparing reproductive traits of the dominant cladoceran species (Bosmina and Daphnia) in lochs with and without fish.
Cladocerans in lochs with fish have more rapid reproductive cycles and higher fecundity parameters, probably in response to the increased threat of predation. These effects remain evident in Bosmina after they have been raised through three generations in the laboratory, supporting the hypothesis that they have a genetic basis and are not a plastic response to predator presence. Life-history variables of cladocerans were also related to abiotic and biotic variation among lochs, including depth, pH, chlorophyll levels and the concentration of alkaline metals.
I also demonstrate that stickleback have diversified greatly among lochs in functional trophic traits that determine the efficiency of feeding on different types of prey, which could affect total primary production and the structure of prey communities. Ancestral stickleback populations have adapted according to the type of habitat colonised. Fish feed on benthic prey in shallow lochs, which requires greater effort for successful foraging than that required by fish that feed on planktonic prey. I found that variation in stickleback trophic traits was related to both abiotic and biotic variation among lochs, including loch depth and the mean contributions of planktonic and benthic prey to diet.
The results presented in this thesis suggest the possibility of eco-evolutionary feedbacks in these simple ecosystems on North Uist based on the significant responses in fish and zooplankton communities. The thesis also provides a basis for further studies on fish-zooplankton interactions on North Uist and contributes to the wider body of knowledge concerning the relevance of natural variation in shaping the foraging mechanisms of animals
From toxic ornamental to therapeutic prospect: Phytochemical profile and cytotoxic evaluation of n-hexane extract from Iraqi Senecio rowleyanus
No full textSenecio rowleyanus H. Jacobsen plant belongs to Asteraceae family that contain over 1600 genera and approximately 2500 species that have important pharmacological roles in human life. This study assesses the n-hexane extract of Senecio rowleyanus, introduces a new CombiFlash-based method for phytochemical isolation and evaluates its pharmacological effect against breast cancer cells. The whole plant was extracted using maceration in n-hexane and analyzed by Gas Chromatography- Mass Spectrometry (GC-MS). Phytosterols were isolated using CombiFlash column chromatography, yielding several fractions; only fraction B matched lupeol, confirmed by HPLC and FT-IR. Cytotoxicity of the extract was evaluated using the MTT assay on AMJ13 breast cancer cells treated with concentrations (1000, 500, 250, 125, 62.5 and 31.75 µg/mL) for 72 hrs, with doxorubicin as a control. Cell viability was then assessed. GC-MS analysis confirmed the presence of multiple bioactive phytosterols, which revealed a high content of β- and γ-sitosterol (17 %), spathulenol (13 %) and α-amyrin (9 %). with lupeol identified in a specific purified fraction. The n-hexane extract exhibited a cytotoxic effect on AMJ13 cells with an IC₅₀ value of 125.3 μg/mL, showing a concentration- and time-dependent reduction in cell viability. The observed cytotoxicity was notable when compared to the standard drug, doxorubicin. Senecio rowleyanus cultivated in Iraq demonstrates potent anticancer potential, with lupeol and other phytosterols exhibiting significant cytotoxicity against breast cancer cells. These findings support its promise as a natural candidate for pharmaceutical development, further mechanistic and clinical investigations is requiring
Keanekaragaman Makroinvertebrata di Sungai Kampai, Bengkulu
No full text AbstrakPenelitian ini bertujuan untuk menganalisis keanekaragaman makroinvertebrata di Sungai Kampai, Bengkulu. Pengambilan sampel dilakukan di tiga stasiun, yaitu Muara Simpur, Pagar Agung, dan Lubuk Gio dengan dua kali periode sampling setiap stasiun, yaitu April 2019 mengikuti puncak musim hujan dan September 2019 mengikuti puncak musim kemarau. Pengambilan sampel makroinvertebrata menggunakan metode three minutes sampling. Hasil penelitian ditemukan 501 individu makroinvertebrata yang terdiri dari 25 spesies (24 genus; 22 famili; 5 kelas; 4 filum). Epeourus aculeatus merupakan spesies dengan kelimpahan relatif tertinggi secara keseluruhan, yaitu sebesar 62,08%. Indeks keanekaragaman (H’) berturut-turut adalah 1,72; 1,13; 1,80 mengindikasikan bahwa Sungai Kampai mengalami degradasi ringan. Jumlah individu Ephemeroptera, Plecoptera, dan Trichoptera (EPT) per stasiun dari hulu ke hilir adalah 128; 196; dan 20 dengan Indeks Biotik Famili (IBF) adalah 3,34; 4; dan 4. Berdasarkan gabungan dari beberapa indeks ini menunjukkan bahwa kondisi Sungai Kampai masih tergolong sangat baik.AbstractThis research aims to analyze macroinvertebrate diversity in the Kampai River, Bengkulu. Sampling was carried out at three stations, namely Muara Simpur, Pagar Agung, and Lubuk Gio with two sampling periods for each station, namely April 2019 following the peak of the rainy season and September 2019 following the peak of the dry season. Macroinvertebrate sampling used the three minutes sampling method. The research results found 501 macroinvertebrate individuals consisting of 25 species (24 genera; 22 families; 5 classes; 4 phyla). Epeourus aculeatus is the species with the highest relative abundance overall, namely 62.08%. The diversity index (H\u27) is 1.72; 1.13; 1.80 indicates that the Kampai River is experiencing mild degradation. The number of Ephemeroptera, Plecoptera and Trichoptera (EPT) individuals per station from upstream to downstream is 128; 196; and 20 with a Biotic Family Index (IBF) of 3.34; 4; and 4. Based on a combination of several indices, it shows that the condition of the Kampai River is still considered very good.
Injuries Reported by Selected Health Facilities During the Arbaeenia Mass Gathering at Babel Governorate, Iraq, 2014: Retrospective Records Analysis (Preprint)
No full text
BACKGROUND
Arbaeenia is the largest religious mass gathering in Iraq. The conditions associated with mass gatherings result in high rates of injury. There have been no prior studies on injuries during the Arbaeenia mass gathering.
OBJECTIVE
This study describes the injuries observed during the Arbaeenia mass gathering in Babel Governorate in Iraq between November 24 and December 14, 2014.
METHODS
The study was conducted in Babel Governorate at the emergency departments of six public hospitals and two major temporary medical units that were located along the three roads connecting the Middle and Southern Iraqi governorates. We used the Iraq Injury Surveillance System modified form to collect information on injured patients treated in the selected facilities. Data on fatal injuries was obtained from the coroner’s office. The following data were collected from the patients: demographics, outcome of injury, place and time of occurrence, mode of evacuation and medical care before arriving at the hospital, duration of travel from place of occurrence to hospital, disposition of non-fatal injury, cause and mode of injury, and whether the injury occurred in connection with the Arbaeenia mass gathering.
RESULTS
Information was collected on 1564 injury cases, of which 73 were fatal. About half of the reported nonfatal injuries, 687/1404 (48.9%), and a quarter of fatalities, 18/73 (25%) were related to the Arbaeenia mass gathering (<i>P</i>&lt;.001). Most of the reported injuries were unintentional, 1341/1404 (95.51%), occurred on the street, 864/1323 (65.6%), occurred during the daytime 1103/1174 (93.95 %). Most of those injured were evacuated by means other than ambulance 1107/1206 (91.79%) and did not receive pre-hospital medical care 788/1163 (67.7%). Minor injuries 400/1546 (25.9%) and traffic accidents 394/1546 (25.5%) were the most common types of injuries, followed by falls 270/1546 (17.5%). Among fatal injuries, traffic accidents 38/73 (52%) and violence 18/73 (25%) were the leading causes of death. Mass gathering injuries were more likely to occur among individuals aged 21-40 years (odds ratio [OR] 3.5; 95% CI 2.7-4.5) and &gt;41 years (OR 7.6; 95% CI 5.4-10.6) versus those &lt;21 years; more likely to be unintentional than assault (OR 5.3; 95% CI 1.8-15.5); more likely to happen on the street versus at home (OR 37.7; 95% CI 22.4-63.6); less likely to happen at night than during the day (OR 0.2; 95% CI 0.1-0.4); and less likely to result in hospital admission (OR 0.5; 95% CI 0.3-0.7).
CONCLUSIONS
The study shows that most injuries were minor, unintentional, and nonfatal, and most people with injuries had limited access to ambulance transportation and did not require hospitalization.
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The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017
No full textBackground Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them. Methods For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers. Findings Globally, 14.3 million (95% uncertainty interval [UI] 12.5-16.3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44.6% (42.2-47.0) decline from 25 . 9 million (22.0-29.9) in 1990. Age-standardised incidence rates declined by 54 . 9% (53 . 4-56.5), from 439.2 (376.7-507.7) per 100 000 person-years in 1990, to 197.8 (172.0-226.2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76.3% (71.8-80.5) of cases of enteric fever. We estimated a global case fatality of 0.95% (0.54-1.53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135.9 thousand (76.9-218.9) deaths from typhoid and paratyphoid fever globally in 2017, a 41.0% (33.6-48.3) decline from 230.5 thousand (131.2-372.6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9.8 million (5.6-15.8) DALYs in 2017, down 43.0% (35.5-50.6) from 17.2 million (9.9-27.8) DALYs in 1990. Interpretation Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.N
The global burden of typhoid and parathypoid fevers: a systematic analyses for the Global Burden of Disease Study 2017
No full textBackground Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and
the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden
from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to
produce them.
Methods For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by
country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of
typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers
using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently
high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted
life-years (DALYs) for typhoid and paratyphoid fevers.
Findings Globally, 14·3 million (95% uncertainty interval [UI] 12·5–16·3) cases of typhoid and paratyphoid
fevers occurred in 2017, a 44·6% (42·2–47·0) decline from 25·9 million (22·0–29·9) in 1990. Age-standardised
incidence rates declined by 54·9% (53·4–56·5), from 439·2 (376·7–507·7) per 100000 person-years in 1990, to
197·8 (172·0–226·2) per 100 000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused
76·3% (71·8–80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54–1·53) in 2017, with
higher case fatality estimates among children and older adults, and among those living in lower-income countries.
We therefore estimated 135·9 thousand (76·9–218·9) deaths from typhoid and paratyphoid fever globally in 2017, a
41·0% (33·6–48·3) decline from 230·5 thousand (131·2–372·6) in 1990. Overall, typhoid and paratyphoid fevers were
responsible for 9·8 million (5·6–15·8) DALYs in 2017, down 43·0% (35·5–50·6) from 17·2 million (9·9–27·8) DALYs
in 1990.
Interpretation Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death,
with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain
essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young
children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to
drive the greatest improvements in the global burden of the diseas
Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
No full textBackground: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. Methods: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. Findings: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. Interpretation: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed. Funding: Bill & Melinda Gates Foundation
Global, regional, and national age-sex specifc mortality for 264 causes of death, 1980-2016: A systematic analysis for the Global Burden of Disease Study 2016
No full textBackground: Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specifc mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods: We estimated cause-specifc deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specifc causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specifc deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings: The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2-73·2) of deaths in 2016 with 19·3% (18·5-20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00-8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006-16 - age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176-181) increase in deaths in ages 90-94 years and a 210% (208-212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL signifcantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the fve leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a fner level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation: The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and confict and terrorism. Increasing levels of YLLs might refect outcomes from conditions that required high levels of care but for which efective treatments remain elusive, potentially increasing costs to health systems
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