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Long QT syndrome : the identification and verification of putative KCNE2-interacting proteinsNeethling, Annika 12 1900 (has links)
Thesis (MScMedSc)-- Stellenbosch University, 2013. / ENGLISH ABSTRACT: Long QT syndrome (LQTS) is a cardiac repolarization disorder affecting every 1:2000-1:3000 individuals. This disease is characterized by a prolonged QT interval on the surface electrocardiogram (ECG) of patients. Symptoms of LQTS range from dizziness and syncope to more severe symptoms such as seizures and sudden cardiac death (SCD). Clinical features of LQTS are a result of the precipitations of Torsades de Pointes, which is a polymorphic form of ventricular tachycardia. A number of genetic forms of LQTS have been identified with more than 700 mutations in 12 different genes leading to disease pathogenesis. However it has been estimated that approximately 25% of patients with compelling LQTS have no mutations within the known LQT genes. This proves to be problematic since treatment regimens depend on the genetic diagnosis of affected individuals. Of the known mutated genes, KCNE2 is associated with LQT6. KCNE2 encodes the beta-subunit of potassium ion channel proteins. These proteins contain cytoplasmic C-terminal domains in which many mutations have been identified.
We hypothesize that genes encoding KCNE2-interacting proteins might be identified as disease-causing or modifying genes. The present study aimed to use yeast two-hybrid (Y2H) methodology to screen a pre-transformed cardiac cDNA library in order to identify putative interactors of the C-terminal of KCNE2. Through specific selection methods the number of KCNE2 ligands was reduced from 296 to 83. These interactors were sequenced and 14 were identified as putative interacting proteins. False positive ligands were excluded based on their function and subcellular location. Ultimately three strong candidate ligands were selected for further analysis: Alpha-B crystallin (CRYAB), Filamin C (FLNC) and voltage-dependent anion-selective channel protein 1 (VDAC1). Three-dimensional (3D) co-localization and co-immunoprecipitation were used to verify these proposed interactions and succeeded in doing so.
The genes encoding verified interactors will be screened in our SA panel of LQT patients, to potentially identify novel LQT causative or modifying genes. Furthermore, the interactions verified in the present study may shed some light on the mechanism of pathogenesis of LQT causative mutations in KCNE2. / AFRIKAANSE OPSOMMING: Lang QT-sindroom (LQTS) is 'n hart her-polariserende siekte wat elke 1:2000-1:3000 individue affekteer. Hierdie siekte word gekenmerk deur 'n lang QT-interval op die oppervlak elektrokardiogram (EKG) van pasiënte. Simptome van LQTS wissel van duiseligheid en floutes tot meer ernstige simptome soos stuiptrekkings of aanvalle en skielike kardiale dood (SKD). Kliniese kenmerke van LQTS is 'n gevolg van die neerslag van Torsades de Pointes; 'n polimorfiese vorm van ventrikulêre tagikardie. Verskeie genetiese vorms van LQTS is geïdentifiseer met meer as 700 mutasies in 12 verskillende gene wat lei tot siekte patogenese. Dit is ergter beraam dat ongeveer 25% van pasiënte met dwingende LQTS geen mutasies in die bekend LQT gene besit nie. Dit is problematies aangesien siekte behandeling af hang van die genetiese diagnose van geaffekteerde individue. Een van die bekende gemuteerde gene is KCNE2 wat verband hou met LQT6. KCNE2 kodeer die beta-subeenheid van kalium ioonkanaal proteïene. Hierdie proteïene bevat sitoplasmiese C-terminale waarin baie mutasies alreeds geïdentifiseer is.
Ons veronderstel dat gene wat proteïene kodeer wat met KCNE2 interaksie toon, geïdentifiseer kan word as siekte veroorsaakende of wysigings gene. Die huidige studie het die gis twee-hibried metode gebruik om 'n vooraf-getransformeerde hart cDNS biblioteek te sif om vermeende protein interaksies van die C-terminaal van KCNE2 te identifiseer. Deur middel van seleksie metodes is die aantal KCNE2 ligande verminder van 296 tot 83. Die identiteit van die proteïene is bekend gemaak deur volgorderbepaling waarna 14 geïdentifiseer is as proteïene wat moontlik interaksie kan toon met KCNE2. Vals positiewe ligande is uitgesluit op grond van hul funksie en subsellulêre lokasering. Drie kandidaat ligande is gekies vir verdere analise: Alfa-B crystallin (CRYAB), Filamin C (FLNC) en spanning-afhanklike anioon-selektiewe kanaal proteïen 1 (VDAC1). Drie-dimensionele (3D) mede-lokalisering en mede-immunopresipitasie tegnieke is gebruik om hierdie voorgestelde interaksies te verifieer en het geslaag om dit te doen.
Die gene wat geverifieerde proteïene kodeer, sal gekeur word in ons Suid-Afrikaanse paneel van LQT pasiënte om sodoende potensieel nuwe LQT veroorsakende of wysigings gene te identifiseer. Verder kan die geverifieer interaksies in die huidige studie lig werp op die meganisme van die ontstaan van LQT veroorsakende mutasies in KCNE2. / Harry Crossley Foundation (South Africa) / Stellenbosch University / South African Council for Scientific and Industrial Research / Stella and Paul Loewenstein Charitable and Educational Trust
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The role of the cumulus oophorus complex during spermatozoa capacitational eventsRijsdijk, Michelle 12 1900 (has links)
Thesis (MScMedSc (Obstetrics and Gynaecology))--University of Stellenbosch, 2005. / Chapter 1 contains a review dealing with nuclear and morphological changes during spermatogenesis and spermatozoa transport with emphasis on the maturation of spermatozoa, capacitation, acrosome reaction and the interaction with the cumulus oophorus complex (COC). The oocyte and cumulus oophorus complex is also discussed particularly on the topic of maturity (oocyte and cumulus maturity). Also presented is a review of the fluorescent binding agents, namely Fluorescein Isothiocyanate labeled with Pisum sativum (FITC-PSA), Chlorotetracycline test (CTC) and Chromomycin A3 (CMA3). Chapter II describes all the materials and methods used during this study. Routine semen analysis is described with emphasis on normal spermatozoon morphology according to strict criteria. The evaluation of capacitation and acrosome reaction (AR) using the CTC and PSA-FITC staining methods as well as the evaluation of spermatozoon nuclear chromatin packaging using the CMA3 staining method is described. Chapter III represents the results recorded in this study. Compared with those spermatozoa cultured in medium alone, spermatozoa exposed to the cumulus mass were more likely to be capacitated and acrosome reacted, with a distinct increase in chromatin packaging quality. A general discussion of the results and future applications are discussed in Chapter IV. In short An in vitro model for spermatozoa penetration through the cumulus oophorus was established. The model can be applied to investigate the effect of the cumulus oophorus on sperm functions and to assist in the selection of functional sperm for intracytoplasmic sperm injection therapy. All relevant references are presented in Chapter V .
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Early human follicle ultrastructure comparison after slow cryopreservation in two different cryoprotectantsEls, Cecilia Lydia 03 1900 (has links)
Thesis (MScMedSc (Obstetrics and Gynaecology))--Stellenbosch University, 2008. / BACKGROUND: The cryopreservation and transplantation of ovarian tissue have
been shown to restore ovarian function temporarily and may also preserve the fertility
of young female cancer patients until after their sterilizing cancer treatment. Since
tissue samples are large and morphologically complex, the cryopreservation
methodology is difficult to optimize and standardise. Ovarian tissue cryopreservation
is therefore, still in its experimental stages and is not a routine option offered to
cancer patients.
OBJECTIVES: Our main aim was to initiate, develop and implement a practical
ovarian tissue cryopreservation and re-transplantation protocol which would restore
ovarian function, and possibly fertility, in young female cancer patients undergoing
sterilizing cancer therapies in South Africa. The objective of this study was to
improve the slow cryopreservation protocol for human ovarian tissue. The
ultrastructural effects after cryopreservation with two well-known cryoprotectants,
dimethyl sulfoxide (DMSO) and 1,2-propylene glycol (PROH), on early human
follicles were investigated and compared to identify and the better cryoprotectant.
MATERIALS AND METHODS: A single group experimental study design was used.
The participants consisted cancer patients of the Gynaecological Oncology Unit of
Tygerberg Hospital who entered on a basis of voluntary informed consent. Ovarian
tissue was obtained by laparoscopic oophorectomy. After dissection of the
ovary(ies), some fresh cortical tissue was sent for metastatic analysis and a few
strips taken as fresh control. Remaining dissected ovarian cortical tissue sections of
each patient were equally divided into the two cryoprotectant groups. Five resulting
groups could be compared: i) fresh tissue (control group); tissue equilibrated in ii)
DMSO; or iii) PROH and tissue equilibrated and cryopreserved in iv) DMSO or v)
PROH. Five tissue samples per patient were therefore fixed for standard histological
haematoxylin and eosin (HE) staining and transmission electron microscopy (TEM).
Tissue samples showing early follicles on HE slides were sent for TEM processing.
Ultrastructural studies on micrographs of primordial and primary follicles were
assessed according to a scoring system which gave an indication of follicular health.
Appropriate statistical tests were applied to analyse the mean scores where P≤0.05
was considered as statistically significant. RESULTS: No significant overall cryopreservation treatment effect was evident in
any of the follicular ultrastructures evaluated. This result indicated that the
cryopreservation protocol used did not induce significant damage to the cortex tissue
compared to the fresh control group. Comparison of the effect of PROH and DMSO
on the follicular ultrastructures showed that PROH tend to induce more extensive
damage, especially after cryopreservation. Correlation studies showed significant
positive relationships between the majority of the evaluated ultrastructures, especially
between the oocyte and granulosa cell layer and basal membrane. The stromal cells
and extracellular matrix did not correlate well with other structures. Correlations
indicated that the granulosa cells, oocyte and basal lamina are affected similarly and
that the damage in one of these structures may be representative of the damage in
the other structures.
CONCLUSION: The main aim of the study was achieved since results showed that
no significant damage was induced by the cryopreservation protocols. Ovarian tissue
cryopreserved in this study has shown to restore endocrine function temporarily after
heterotopic autotransplantation in menopausal patients. From the electron
microscopy evaluations, DMSO showed better cryopreservation results. The DMSO
cryopreservation protocol was also more time efficient and has shown the most
successful outcomes in the literature. The stromal tissue seemed to be affected
differently by cryopreservation compared to the primordial follicle ultrastructures.
Younger patients are needed for future studies since a larger initial follicular reserve
may allow for larger follicle sample sizes.
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The impact of a sensory developmental care programme for very low birth weight preterm infants in the neonatal intensive care unit.Nieder-Heitmann, Esther 03 1900 (has links)
Thesis (MOccTher (Interdisciplinary Health Sciences. Occupational Therapy))--University of Stellenbosch, 2010. / AFRIKAANSE OPSOMMING: AGTERGROND
Dit is bekend dat vroeggebore babas met ʼn baie lae geboortemassa ʼn hoër
insidensie van ontwikkelings-, gedrags- en mediese agterstande en verskeie
leerprobleme toon teen die tyd dat hulle skoolgaande ouderdom bereik. Kommer
bestaan ook oor die omgewingseffek van die neonatale intensiewe sorgeenheid op
die sensoriese ontwikkeling van die vroeggebore baba en hoe dit tot bogenoemde
agterstande kan bydra. Daar is verskillende benaderings wat daarop aanspraak
maak dat hulle die probleem kan oplos, met kangaroemoedersorg (‘kangaroo mother
care’) en ontwikkelingsorg (‘developmental care’) wat in die literatuur uitgesonder is
as besonders belowend. Met die aanvang van hierdie studie was daar nog geen
empiriese studies in die literatuur gerapporteer wat enige aansprake van hierdie
benaderings bevestig het nie. Daar was dus ʼn behoefte vir ʼn empiries-nagevorsde
program wat prakties in die neonatale intensiewe eenheid toegepas kon word met die
oog op die vermindering van omgewingstressors ten opsigte van die vroeggebore
baba se sensoriese sisteme.
DOEL
Die doel met die studie was om die invloed te bepaal van ʼn Sensoriese Ontwikkelingsorgprogram
(‘Sensory Developmental Care Programme’), wat ʼn spesifieke kangaroemoedersorg-
protokol insluit, op die sensoriese ontwikkeling van die vroeggebore
baba met 'ʼn baie lae geboortemassa tot en met die ouderdom van 18 maande
(gekorrigeerde ouderdom).
METODOLOGIE
ʼn Ewekansig-gekontroleerde studie is uitgevoer. Die studiesteekproef het bestaan uit
89 vroeggebore babas met ʼn baie lae geboortemassa wat in ʼn periode van 24
maande toegelaat is tot die neonatale eenheid van Tygerberg Hospitaal in Kaapstad,
Suid-Afrika. Die babas is gewerf op grond van sekere kriteria en is dan daarna
ewekansig aan een van twee groepe toegeken: 1) die intervensiegroep het sorg
ontvang volgens die Sensoriese Ontwikkelingsorgprogram vir 10 dae; en 2) die
kontrolegroep het ook vir 10 dae die standaardsorg van die eenheid ontvang. Die
intervensiegroep het uit 45 babas bestaan, van wie 22 die studie voltooi het, terwyl
die kontrolegroep uit 44 babas bestaan het van wie 20 die studie voltooi het. Beide
studiegroepe is opgevolg op 6, 12 en 18 maande (gekorrigeerde ouderdom), by
welke geleentheid die Sensoriese Funksietoets vir Babas (‘Test of Sensory Functions
in Infants’) telkens toegepas is vir die assessering van sensoriese ontwikkeling. Op
18 maande (gekorrigeerde ouderdom) is ʼn assessering met die Griffiths
Ontwikkelingskaal ook gedoen om funksies in die ander ontwikkelingsareas van die
babas te bepaal. Toetsresultate is geanaliseer met behulp van herhaalde ANOVAmetings
en die Bonferoni t-prosedure om die effek van die Sensoriese
Ontwikkelingsorgprogram op die sensoriese ontwikkeling van die babas tot en met
18 maande (gekorrigeerde ouderdom) te bepaal.
RESULTATE
Die resultate van die vergelyking van die prestasie van beide groepe (groep-effek),
gemeet met behulp van die Sensoriese Funksietoets vir Babas, is van groot belang
vir hierdie studie. Die intervensiegroep het betekenisvol verskil op die totale telling
(p<0.00), sowel as op die volgende vier van die vyf subtoets-tellings: respons op
diepdruk (‘tactile deep pressure’) (p<0.03); motoriese aanpassingsreaksies (p<0.03);
visuele tas-integrasie (p<0.00); en respons op vestibulêre stimulasie (p<0.01).
GEVOLGTREKKING
Die resultate van die studie dui aan dat die babas in die intervensiegroep baat gevind
het by die Sensoriese Ontwikkelingsorgprogram met betrekking tot hul sensoriese
funksies tot en met die ouderdom van 18 maande (gekorrigeerde ouderdom). Die
Sensoriese Ontwikkelingsorgprogram het geblyk prakties sowel as suksesvol te
wees met betrekking tot sy doel. Die Program sou daarom met vrug in ander
neonatale intensiewe sorgeenhede aangewend kon word. / ENGLISH ABSTRACT: BACKGROUND
Premature infants of very low birth weight are known to be inclined to developmental,
medical, behavioural and various learning deficiencies by the time they reach schoolgoing
age. Concerns have been raised about the effect of the neonatal intensive care
unit environment on the sensory development of the premature infant and how this
could contribute to these deficiencies. Various approaches claim to address this
problem, of which kangaroo mother care and developmental care have in the
literature been singled out as particularly promising. However, at the commencement
of this study no empirical studies had been reported in the literature to confirm any of
the claims of these approaches. Therefore, a need existed for an empirically
researched programme that could be practically applied in the neonatal intensive
care unit with a view to reducing environmental stressors regarding the sensory
systems of the premature infant.
AIM
The aim of this study was to determine the influence of a Sensory Developmental
Care Programme, which incorporated a specific kangaroo mother care protocol, on
the sensory development of the very low birth weight premature infant, up to the age
of 18 months (corrected age).
METHODOLOGY
A randomised controlled study was conducted. The study sample consisted of 89
very low birth weight premature infants, admitted during a 24-month period to the
neonatal care unit at Tygerberg Hospital in Cape Town, South Africa. The infants
were recruited by means of certain criteria and then randomly assigned to one of two
groups: 1) the intervention group was cared for according to the Sensory
Developmental Care Programme for ten recorded days; and 2) the control group that
received the standard care of the unit, also for ten days. The intervention group
consisted of 45 infants of whom 22 completed the study, while the control group
consisted of 44 infants of whom 20 completed the study. Both study groups were
followed up at six, 12 and 18 months (corrected age) when the Test of Sensory
Functions in Infants was used to do a sensory developmental assessment. At 18
months (corrected age) a Griffiths Developmental Scale assessment was also
conducted to determine function in other areas of development. Test results were
analysed using repeated measures of ANOVA, and the Bonferoni t procedure to
determine the effect that the Sensory Developmental Care Programme had on the
sensory development of the infant up to 18 months (corrected age).
RESULTS
The results of the comparison of the performance of both groups (group effect),
measured by the Test of Sensory Functions in Infants are of great importance to this
study. The intervention group had a significant difference on the total score (p<0.00),
as well as on the following four of the five sub-tests scores: reactivity to tactile deep
pressure (p<0.03); adaptive motor functions (p<0.03); visual-tactile integration
(p<0.00); and reactivity to vestibular stimulation (p<0.01).
CONCLUSION
The results of this study signify that the infants in the intervention group benefited
from the Sensory Developmental Care Programme concerning their sensory
functions up to the age of 18 months (corrected age). The Sensory Developmental
Care Programme was demonstrated to be both practical and successful in terms of
its aims. The Programme could therefore be fruitfully utilised in other neonatal
intensive care units.
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Pre- and post-test results of the cognitive functioning level of workers with intellectual impairment after the implementation of a structured activity programme in a protective workshopGoliath, Charlyn Delmarie 12 1900 (has links)
Thesis (MA)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: Acknowledgement of the right to equal work opportunities for people with disabilities is
widely supported in South Africa. Several policy documents and laws have been
published since July 1993 and provide clear guidelines regarding equal opportunities for
people with disabilities.
A state subsidy scheme for protective workshops was introduced for the first time on
1 April 1997 (Operational Manual for Protective Workshops, 2001: 1). The purpose of
this subsidy scheme was to provide work opportunities for people who cannot enter the
sheltered or open labour market due to the effect of their disabilities on their daily
functioning. In March 2001, the Department of Social Development and Poverty
Alleviation in the Western Cape introduced a draft document, Operational Manual for
Protective Workshops. The aim of the manual focused on the development of the
worker role and economic empowerment of people with disabilities who work in
protective workshops.
Due to ignorance, fear and stereotyping, persons with intellectual impairment are being
unfairly discriminated against in society and at the workplace. With reasonable
accommodation, persons with intellectual impairment are able to demonstrate their work
ability and contribute equally in the workplace. Persons with intellectual impairment
contribute to the economy and society by means of their service in protective
workshops.
The aim of the study was to investigate whether the structured activity programme
implemented in a protective workshop in the Western Cape brought a change to the
level of cognitive functioning of workers with intellectual impairment as assessed by the
Allen Cognitive Level Screen (ACLS), with the purpose of making recommendations
regarding the sustainability and extension of the structured activity programme.
Pre- and post-tests of the workers' cognitive functioning were done to determine
whether the implemented structured activity programme had an effect on the cognitive
functioning level of the workers. The ACLS was used as measurement instrument and a
hypothesis was stated:
HO - There is no change in the level of cognitive functioning of the workers after
participation in a structured activity programme.
H1 - There is a change in the level of cognitive functioning of the workers after
participation in a structured activity programme.
The Functional Information Processing Model (FIPM) was used as a frame of reference
in the development of the structured activity programme for the occupational group. The
structured activity programme was implemented and after one year and six months a
post-test was done on the workers in the occupational group.
The null hypothesis was accepted as p=O.28.A 95% confidence interval was indicated.
The post-test indicated that there was no significant change in the cognitive levels of the
workers in the occupational group after implementation of a structured activity
programme. This could have resulted from the study sample being too small. Although
the change was not statistically significant. it indicated that learning did occur on an
Allen Cognitive Level (ACL) 3. It is recommended that the study to be replicated at other
protective workshops that may provide a bigger sample to confirm the amount of
learning that takes place. / AFRIKAANSE OPSOMMING: Erkenning van persone met gestremdhede se gelyke reg tot indiensneming word sterk
in Suid-Afrika ondersteun. Verskeie beleidsdokumente en werkstukke is sedert Julie
1993 gepubliseer wat duidelike riglyne aangaande hierdie standpunt stel.
'n Staatsubsidieskema vir beskermde werkwinkels is vanaf 1 April 1997 vir die eerste
keer beskikbaar gestel (Operational Manual for Protective Workshops, 2001: 1). Die
doel van hierdie skema is om werksgeleenthede te verskaf aan persone wat as gevolg
van hul graad van gestremdheid nie die beskutte arbeids- of ope arbeidsmark kan
betree nie. In Maart 2001 het die Departement van Sosiale Dienste, Wes-Kaap, 'n
voorlopige dokument, Operational Manual for Protective Workshops, bekendgestel, wat
fokus op die ontwikkeling van werksvaardighede en die ekonomiese bemagtiging van
persone met gestremdhede in beskermde werkwinkels.
Weens onkunde, vrees en stereotipering word daar onregverdig gediskrimineer teen
persone met intellektuele gestremdheid in die samelewing, asook in die werksplek.
lndien persone met intellektuele gestremdheid billik geakkommodeer word, sal hulle hul
werkvermoëns demonstreer en sal hulle 'n gelyke bydrae kan lewer in die werksplek.
Persone met intellektuele gestremdheid lewer 'n bydrae tot die ekonomie en die
samelewing deur hul diens in beskermde werkwinkels.
Die doel van die studie was om ondersoek in te stelof die gestruktureerde
aktiwiteitsprogram, soos aangebied in 'n beskermde werkswinkel in die Wes-Kaap, 'n
verandering in die kognitiewe funksioneringsvlakke van werkers met intellektuele
gestremdheid, soos bepaal deur die Allen Cognitive Level Screen (ACLS),
teweeggebring het ten einde aanbevelings te maak oor die uitbreiding en
volhoubaarheid van die program.
Voor- en na-toetse van die werkers se kognitiewe funksioneringsvlakke is gedoen om te
bepaal of die gestruktureerde aktiwiteitsprogram enige verskil in hul kognitiewe
funksionering gemaak het. Die Allen Cognitive Level Screen- (ACLS-)toets is as 'n
meetinstrument gebruik en 'n hipotese is gestel:
HO - Daar is geen verandering in die werkers se kognitiewe funksioneringsvlak na
deelname aan 'n gestruktureerde aktiwiteitsprogram nie.
H1 - Daar is 'n verandering in die werkers se kognitiewe funksioneringsvlak na
deelname aan 'n gestruktureerde aktiwiteitsprogram.
Die Functional Information Processing Model (FIPM) is gebruik as 'n
verwysingsraamwerk vir die ontwikkeling van die gestruktureerde aktiwiteitsprogram.
Die gestruktureerde aktiwiteitsprogram is geïmplementeer en 'n na-toets is na 'n jaar en
ses maande op die werkers in die gestruktureerde aktiwiteitsprogram gedoen.
Die nulhipotese is aanvaar aangesien p=O.28. 'n Sekerheidsinterval van 95% is
aangetoon. Die na-toets het getoon dat daar geen statisties beduidende verskil was in
die verandering van die kognitiewe vlakke van die werkers in die aktiwiteitsgroep na
implementering van 'n gestruktureerde aktiwiteitsprogram nie. Die resultaat kan die
gevolg wees van 'n te klein steekproef. Alhoewel die verandering in kognitiewe vlak nie
statisties beduidend was nie, het daar tog 'n mate van leer op 'n Allen Cognitive Level
(ACL) 3 by die werkers plaasgevind. Dit word voorgestel dat hierdie studie herhaal word
by ander beskermde werkswinkels wat 'n groter steekproef kan lewer om die mate van
leer wat plaasvind, te bevestig.
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A critical review of the validity of the Credibility Assessment Tool (CAT) and its application to the screening of suspected malingeringTheunissen, Karen Sunette 03 1900 (has links)
Thesis (MOccTher)-- University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Malingering, the intentional simulation or exaggeration of symptoms for secondary gain, has a
significant financial impact on disability insurance given its prevalence. Multidisciplinary
professionals involved in disability determination therefore require a tool which would assist in the
screening of suspected malingerers.
AIM: The Credibility Assessment Tool (CAT), a tool which was developed as part of the
Performance APGAR, was reviewed in terms of its validity and application to the screening of
malingering. Research objectives included the review of face and content validity through a
literature review and concept analysis, as well as the review of construct and concurrent validity by
comparing the results with the operationalised malingering construct and available malingering
protocols. The adapted Slick criteria as proposed by Aronoff, applicable to chronic pain,
neurocognitive, neurological and psychiatric symptoms, was identified as the most suitable
criterion standard for use of comparison.
DESIGN: The research design was a descriptive analytical design, which was performed
retrospectively with a report review from insurance referrals to the researcher. Informed consent
was obtained from insurers who legally own the reports. A saturated sample of convenience of
184 cases with depression and pain as predominant symptoms were analysed. Recall bias were
minimised through omission of personal identifiers and the use of a peer check of 20 random
cases. Results in the peer check were suggestive of poor inter-rater reliability, rather than recall
bias.
METHOD: Cases were analysed according to the guidelines from the respective authors of the
CAT and adapted Slick criteria, however this was further defined to ensure that the study could be
replicated.
RESULTS: Face validity was adequate in terms of purpose, item selection and association
between consistency criteria, however require improvement in terms of standardised instruction
and weighting of the scale. Content validity was rated as adequate to excellent, given that it
supports criteria linked to the malingering construct. Construct validity was adequate as
demonstrated by association between concepts obtained through concept analysis. Correlation
between the CAT and adapted Slick was strong (r>0.5) however caution is expressed that this
requires further research.
CONCLUSION: Recommendations for further research included the review of content validity with
subject experts, criterion and predictive valid through a case-control study of known-groups, as
well as the reliability of the CAT, and the use of specialised ADL indices for malingering detection.
Adaptation to the CAT was depicted in the proposed Consistency Assessment Tool. / AFRIKAANSE OPSOMMING: Malingering, die opsetlike nabootsing of oordrywing van simptome vir sekondêre gewin, het ‘n
beduidende finansiële impak op ongeskiktheidsversekering as gevolg van die prevalensie daarvan.
Multidissiplinêre professionele persone betrokke by ongeskiktheidsevaluasies het daarom ‘n
meetinstrument nodig om moontlike malingeerders te identifiseer.
DOEL: Die Credibility Assessment Tool (CAT), wat ontwikkel was as deel van die Performance
APGAR, was ondersoek in terme van geldigheid en toepassing op malingering.
Navorsingsdoelwitte het die ondersoek van voorkoms- en inhoudsgeldigheid deur ‘n
literatuurstudie en konsep analise behels, sowel as konstruk- en korrelasie geldigheid deur die
vergelyking van die resultate met beskikbare malingering protokolle en operasionele konstrukte.
Die aangepaste Slick kriteria soos voorgestel deur Aronoff, wat toepaslik is op kroniese pyn,
neurokognitiewe, neurologiese en psigiatriese simptome, was ge-identifiseer as die meeste
gepaste kriterium standaard vir vergelyking.
ONTWERP: Die studieontwerp was ‘n beskrywende analitiese studie wat retrospektief uitgevoer
was deur ‘n ondersoek van verslae van versekeraars. Ingeligte toestemming was verkry van
versekeraars wat die wetlike eienaars van die verslae is. ‘n Gerieflikheidsteekproef van 184 gevalle
met depressie en pyn as hoof simptome was geanaliseer. Sydighede was verminder deur
persoonlike inligting te verwyder en die gebruik van ‘n eweknie evaluasie van 20 ewekansige
getrekte gevalle. Voorlopige resultate dui onbevredigende betroubaarheid aan, eerder as
sydighede.
METODE: Gevalle was ge-evalueer volgends die riglyne van die verskeie outeure van die CAT en
aangepaste Slick kriteria, en was sodanig verder gedefinieer om te verseker dat die studie herhaal
kan word.
RESULTATE: Voorkomsgeldigheid was voldoende, maar verbetering is aanbeveel in terme van
gestandardiseerde instruksie en skaal verdeling. Inhoudsgeldigheid was beduidend in vergelyking
met die wetenskaplike literatuur en die geoperasionaliseerde konstrukte. Konstrukgeldigheid was
bevestig deur die positiewe verhoudings tussen die aangepaste Slick en CAT kriteria. ‘n Sterk
korrelasie was gevind tussen die aangepaste Slick en CAT, maar hierdie moet versigtig geinterpreteer
word aangesien verdere navorsing verlang word.
GEVOLGTREKKING: Aanbevelings vir verdere navorsing sluit in die ondersoek van die
inhoudsgeldigheid met eksperte, kriterium- en voorspellingsgeldigheid, sowel as die
betroubaarheid van die CAT en die gebruik van gespesialiseerde ADL indekse vir uitkenning van
malingering. Aanpassing vir die CAT word ook voorgestel.
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The profile of a surgical ICU in a public sector tertiary hospital in South AfricaHanekom, Susan 12 1900 (has links)
Thesis (MScFisio)--University of Stellenbosch, 2004. / ENGLISH ABSTRACT: Objective: To describe the baseline data of a surgical ICU in South Africa before the
implementation of an evidence-based physiotherapy practice protocol. Design:
Prospective cohort observational study Setting: Ten-bed closed surgical unit in a
university affiliated tertiary hospital. Patients: All adult ICU admissions from 16 June -
30 September 2003. Measurements: The patient’s clinical data including demographic
information, admission diagnosis, surgery classification and co-morbidities were
recorded on admission to the unit. APACHE II score was calculated. The physiotherapy
techniques, positions and functional activities used, the frequency and duration of
physiotherapy treatment sessions, the provision of after-hours service and the diagnosis
of pulmonary complications were also recorded daily. The time of mechanical ventilation
was calculated and the number of re-intubations documented. The ICU length of stay or
mortality was recorded. Results: 160 patients were admitted. Patients were 49 +/-
19.95 years of age. The mean APACHE II score was 12.3 +/ 7.19 and a 12.3% mortality
was observed. Thirty seven percent of patients were admitted to the unit following
elective surgery. Patients stayed in the unit for 5.94 +/- 6.55 days. Hypertension was the
most frequent co-morbidity found in this cohort (42%), and 21% of patients tested,
tested positive for HIV. Co-morbidities had no significant association with ICU LOS or
mortality. Nine hundred and twenty seven physiotherapy records were obtained.
Students were responsible for 39% (n=366) of treatment sessions, the unit therapist for
34% (n=311) and the on-call therapists for 27% (n=250). Despite routine daily
physiotherapy for all patients in the unit, 39% (n=62) developed excessive secretions,
30% (n=48) of patients developed pneumonia and 27% (n=43) of patients were
diagnosed with basal atelectasis. Nineteen patients (12%) died in the ICU. Patients
spent a mean of 5.94 (SD 6.55) days in the unit. One hundred patients (63%) were
ventilated. Almost a third of ventilated patients (31%) were intubated more than once.
The patients spent a mean time of 3.8 days (SD 6.30) on the ventilator every time they
were re-intubated. The development of pulmonary complications significantly increased
the time on the ventilator and the LOS. Conclusions: This baseline study of a surgical
ICU presents a picture of a unit providing care comparable to first world environments.
The picture of the physiotherapy service provided in this unit is of a “traditional” service
based neither on the available evidence regarding the prevention or management of
pulmonary complications, nor on the incorporation of early rehabilitation into the
management of mechanically ventilated adult patients in ICU. / AFRIKAANSE OPSOMMING: Doel: Om die basis lyn van ‘n chirurgiese intensiewe sorg eenheid in Suid Afrika te
beskryf voor die implementering van ‘n bewysgesteunde fisioterapie protokol in die
eenheid. Studie struktuur: Prospektiewe kohort observerende studie. Eenheid: Tien
bed geslote eenheid in ‘n tertiêre opleidingshospitaal. Pasiënte: Alle volwasse pasiënte
opgeneem in die eenheid tussen 16 Junie en 30 September 2003. Meetings:
Demografiese data, diagnose met opname, chirurgie klassifikasie en ko-morbiditeite is
aangeteken by opname. APACHE II is bereken. Die fisioterapie tegnieke, pasiënt
posisies en funksionele aktiwiteite gebruik in behandelingssessies, die frekwensie en
duur van behandelingssessies, die verskaffing van na-ure diens aan die eenheid asook
die komplikasies gediagnoseer is daagliks aangeteken. Die tyd wat pasiënte geventileer
is asook die aantal kere geher-intubeer is bereken. Die tydsduur van eenheid verblyf
asook mortaliteit is aangeteken. Results: 160 pasiënte is opgeneem, met ‘n
gemiddelde ouderdom van 49 +/- 19.95. Die gemiddelde APACHE II telling was 12.3 +/
7.19 en die mortaliteit was 12.3%. Sewe en dertig persent van pasiënte is opgeneem na
elektiewe chirurgie. Pasiënte bly in die eenheid gemiddeld vir 5.94 +/- 6.55 dae.
Hipertensie was die mees algemene ko-morbiditeit (42%), en 21% van die pasiënte wat
getoets is, het positief getoets vir HIV. Ko-morbiditeite het geen beduidende verband
getoon met die tyd in die eenheid of mortaliteit nie. 927 Fisioterapie rekords is
aangeteken. Studente was verantwoordelik vir 39% (n=366) van die
behandelingssessies, die eenheid terapeut vir 34% (n=311) en die op-roep
fisioterapeute vir 27% (n=250). Ten spyte van daaglikse roetine fisioterapie behandeling
van alle pasiënte in die eenheid het 39% (n=62) oormatige sekresies ontwikkel, 30%
(n=48) is met pneumonie gediagnoseer en 27% (n=43) met basale atelektase.
Negentien pasiënte (12%) is dood in die eenheid. Die tydsduur van eenheid verblyf was
5.94 (SD 6.55) dae. Een honderd pasiënte (63%) is geventileer. Byna een derde (31%)
van pasiënte is geher-intubeer. Met elke her-intubasie het die pasiënte gemiddeld 3.8
(SD 6.30) dae langer op die ventilator gebly. Pulmonale komplikasies het beide die
tydsduur in die eenheid as op die ventilator betekenisvol verleng. Gevolgtrekkings:
Hierdie basislyn studie beskryf ‘n eenheid waar pasiënte mediese sorg ontvang
soortgelyk aan eerste wêreld lande. Die fisioterapeutiese diens wat gelewer word is
egter nie gebasseer op die nuutste bewyse in die literatuur nie. Nog, in die voorkoming
of in die behandeling van pulmonale komplikasies, nog in die vroëere inkorporasie van
rehabilitasie in die hantering van volwasse pasiënte in ‘n intensiewe sorg eenheid.
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The validation of the Canadian norms for the Alberta Infant Motor Scale within the Cape MetropolitanManuel, Alana 03 1900 (has links)
Thesis (MScPhysio (Physiotherapy))--University of Stellenbosch, 2010. / Information on the normal gross motor skills in a healthy population is important since normative data provides a benchmark for health professionals to evaluate deviations from the norm. The Alberta Infant Motor Scale (AIMS) was developed to assist with the motor assessment of young infants from birth through to independent walking. The validation of the Canadian cohort for the AIMS needs to be done with regards to infants in South Africa (Cape Town), before it can be utilised by health professionals working in Paediatric Health Care. To determine if the Canadian norms for the AIMS are valid for infants aged 4 - 18 months within the Cape Metropole, South Africa. A prospective descriptive study was conducted to validate the AIMS. A total of 67 infants from one private and one public institution participated in the study. Infants were assessed at 4, 8, 12 and 18 months of age with the AIMS. Results were analysed using ANOVA and t-tests to determine the relationship between age, ethnicity, gender and clinics.The AIMS gross motor scores of this sample of infants were not significantly different from the Canadian norms, bar at 4 months. Female infants performed significantly (p<0.05) better than males at four months. It was not possible to convert the 18 month old infants‟ raw scores into percentile rankings and therefore it could not be compared to the Canadian norms. The results yielded from this study indicate that the AIMS is a valid assessment tool for healthy infants from 8 - 12 months of age within the Cape Metropole, South Africa, however, care should be taken when infants‟ scores at 4 months are compared to the scores of the normative sample. The AIMS can therefore be used by health care professionals at the Baby Well clinics in the Cape Metropole to assess gross motor development in infants for this age group and can consequently refer infants who may display delays in motor development to appropriate paediatric specialists. The results from this pilot study also make provision for future in-depth research on the AIMS with a larger cohort and with more ethnic diversity.
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Ontogeny of the innate immune response in healthy South African infantsAdams, Rozanne Charlene McChary 12 1900 (has links)
Thesis (MScMedSc)--Stellenbosch University, 2012. / Includes bibliography / ENGLISH ABSTRACT: Infection is a major cause of morbidity and mortality in infants within the first few months of life. Susceptibility to infectious disease in this vulnerable population is more prevalent in resource-limited regions, with a higher disease burden. Due to certain deficiencies in their adaptive immune system, neonates rely predominantly on their innate immune system for protection against infection, a vital component in the early host defence against pathogens. Several studies have described differences in neonatal innate toll-like receptor-mediated responses compared to adult counterparts, though very little is known about these receptor responses within resource-limited settings. To address this issue, we assessed the longitudinal development of cytokine-specific responses of TLR4 and TLR7/8 in monocytes, myeloid dendritic cells and plasmacytoid dendritic cells in infants from a resource-limited setting, South Africa, within the first 12 months of life and compared it to adults. Contrary to previously published literature, we observed heightened production of TH-1 cytokines: we showed increased responsiveness to TLR4 and TLR7/8 stimulation in infants at two and six weeks of age, which may be due to vaccination administered at birth. Unexpectedly, the hyper-inflammatory response persisted at six months in response to the LPS (TLR4) stimulus. This increased response at six months may be attributed to decreased passive immunity through infant weaning as well as increased exposure to microbial pathogens in this setting. Maturation of most cytokine responses was reached at twelve months for the TLR4 receptor, and at six months for the TLR7/8 receptor.
The first year of life represents a critical period for maturation of the immune response. Data from this study point towards an elevated response within the first six months of life. This heightened response reflects both an ability to mount a sufficient TH-1 response in infancy, but more likely, the increased exposure to microbial stimuli in the environment. Thus, we speculate that these age-specific inflammatory responses may influence the outcome of immune responses to various vaccines administered, which may result in altered responsiveness to immunisation in infancy. / AFRIKAANSE OPSOMMING: Die hoof oorsaak vir morbiditeit en mortaliteit in babas binne die eerste paar maande van hul lewe word toegeskryf aan infeksie. In hulpbron beperkte gebiede, gekenmerk deur `n groter siektelas, is daar `n verhoogde vatbaarheid vir infeksie in hierdie kwesbare populasie. As gevolg van sekere gebreke in die verworwe immuunstelsel, maak pasgebore babas hoofsaaklik staat op hul aangebore immuunstelsel vir beskerming teen infeksie, ’n belangrike komponent vir die vroeë verdediging teen patogene. Verskeie studies het al die verskille in toll-tipe reseptor (TTR) bemiddelde reaksies tussen pasgebore babas en volwassenes vergelyk, maar nie veel is bekend oor hierdie reaksies in areas waar hulpbronne beperk is nie. Om hierdie kwessie aan te spreek is die longitudinale ontwikkeling van sitokien-spesifieke reaksies van die TTR4 en TTR7/8 reseptore van monosiete, miëloïede en plasmasitoïede dendritiese selle van babas in die hulpborn beperkte land Suid-Afrika, oor die eerste 12 maande geëvalueer en dit vergelyk met volwassenes. In teenstelling met vorige literatuur, het hierdie studie ’n polarisasie tot TH-1-sitokien produksie gevind: verhoogde reaktiwiteit van die TTR4 en TTR7/8 is gevind in babas van twee en ses weke oud, wat gedeeltelik as gevolg van die inenting kan wees wat toegedien was na geboorte. Hierdie hiper-inflammatoriese reaksie teen die TTR4 stimulus (Lipopolisakkaried (LPS), het teen verwagting voortgeduur tot op ses maande en kan toegeskryf word aan die vermindering van passiewe immuniteit deur spening, sowel as die toenemende blootstelling aan mikrobiese patogene in die omgewing. Maturasie vir die meerderheid van die sitokiene reaksies, is bereik op 12 maande vir TTR4, en op ses maande vir TTR7/8. Die eerste lewensjaar is ‘n kritiese periode vir die ontwikkeling van die immuunstelsel. Data van hierdie studie dui op ‘n verhoogde reaksie binne die eerste ses maande van ‘n baba se lewe. Hierdie verhoogde reaksie dui op die vermoë om `n voldoende TH-1 reaksie te ontlok, maar meer waarskynlik, verhoogde blootstelling aan mikrobiese stimuli in die omgewing. Dus spekuleer ons dat hierdie ouderdom-spesifieke reaksies dalk die uitkoms van die immuunreaksie teen verskeie entstof toediening kan beïnvloed in babas.
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Automated sputum screening using the BD FocalPointTM Slide Profiler : correlation with transbronchial and transthoracic needle aspirates in a high risk populationNeethling, Greta Sophie 04 1900 (has links)
Thesis (MMed)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background:
Sputum is a non-invasive, economic investigation whereby bronchogenic carcinoma
can be identified. Manual cytological screening is labour intensive, time-consuming
and requires a continuous high level of alertness. Automation has recently been
successfully introduced in gynaecological cytology. Since sputum samples are similar
to cervical smears, the question arises as to whether they are also suitable for
automated screening.
Objective:
This study presented with various objectives: 1) To test automated sputum screening
using the BD FocalPoint™ Slide Profiler (FP) and compare with manual sputum
screening. 2) To determine the sensitivity and specificity of sputum in identification of
bronchogenic carcinoma. 3) To ascertain if any clinical, radiological or bronchoscopy
findings would be predictors for bronchogenic carcinoma. 4) To determine the
significance of adequacy.
Method: Sputum samples were collected prospectively from patients attending the Division of
Pulmonology at Tygerberg hospital for a transbronchial fine needle aspiration biopsy
(TBNA) or a transthoracic fine needle aspiration biopsy (TTNA) for the period from
2010 to 2012. A pre-bronchoscopy sputum was collected and submitted for
processing. Stained slides were put through the FP for automated screening. After
slides were qualified, sputum slides were put back in the routine screening pool.
Correlation was done using the TBNA/TTNA result as the standard to evaluate the
sputum results. Results:
108 sputum samples were included in this study. Of the 84.3% malignant (n=91) and
15.7% benign (n=17) cases confirmed with a diagnostic procedure, sputum cytology
had a sensitivity of 38.5% (35/91 malignant cases), and a specificity of 100% (17/17
benign cases). Automated screening had a better sensitivity of 94.3% (33/35 positive
sputum cases), while manual screening showed a sensitivity of 74.3% (26/35 positive
sputum cases) when compared to the final sputum result.
Individual parameters with a significant association with positive sputum included the
presence of an endobronchial tumour, partial airway obstruction / stenosis, round
mass, spiculated mass (negative association), loss of weight (negative association)
and squamous cell carcinoma as the histological subtype. Adequacy was not as
significant as hypothesised since 85.3% of true positive sputum, but also 65.5% of
false negative sputum, had large numbers of alveolar macrophages present.
Conclusion:
Sputum cytology remains an important part of the screening programme for
bronchogenic carcinoma in the public health sector of South Africa. Results confirm
that sputum cytology is very specific, and automated screening improves sensitivity.
Automated screening proved to be more time efficient, resulting in 83.1% reduction
(p<0.0001) in the screening time spent per case by a cytotechnologist.
Results confirm that the quantity of alveolar macrophages is not directly proprtional to
pathology representation. Positive sputum results did however improve with sputum
adequacy, but had no significant association.
Recommendations from this study include adopting automated sputum screening. / AFRIKAANSE OPSOMMING: Agtergrond:
Die verkryging van ‘n sputummonster is ‘n nie-indringende, ekonomiese ondersoek
waardeur bronguskarsinoom identifiseer kan word. Nie-geoutomatiseerde sitologiese
ondersoek is arbeidsintensief, tydrowend en vereis ‘n deurlopende hoë vlak van
konsentrasie en fokus. Outomatisering is onlangs suksesvol geïmplementeer in
ginekologiese sitologie-ondersoeke. Aangesien sputummonsters soortgelyk aan
servikale monsters is, het die vraag ontstaan of sputummonsters ook geskik sou
wees vir geoutomatiseerde sifting.
Doelwit:
Hierdie studie het verskeie doelwitte gehad: 1) Om geoutomatiseerde sifting van
sputummonsters te toets deur gebruik te maak van BD Focal Point ™ Slide Profiler
(FP), en te vergelyk met nie-geoutomatiseerde sputum sifting. 2) Om die sensitiwiteit
en spesifisiteit van sputum in die identifikasie van bronguskarsinoom te bepaal. 3)
Om vas te stel of enige kliniese, radiologiese of brongoskopiese bevindings
bronguskarsinoom sou kon voorspel. 4) Om die belang van ‘n verteenwoordigende
monster te bepaal.
Metode:
‘n Prospektiewe studie van die pasiënte wat die Divisie van Pulmonologie by
Tygerberg Hospitaal vir transbrongiale nodale aspirasie (TBNA) of ‘n transtorakale
aspirasie (TTNA) vanaf Julie 2010 tot Mei 2012 bygewoon het, is gedoen. ‘n Prebrongoskopiese
sputum is geneem en gestuur vir prosessering. Die gekleurde
skuifies is deur die FP gestuur vir geoutomatiseerde ondersoek. Indien die
sputumskuifies gekwalifiseer het vir geoutomatiseerde sifting, is hulle in die groep vir
ondersoek ingesluit. ‘n Korrelasiestudie, om die sputumresultate te evalueer, is
uitgevoer deur die TBNA/TTNA bevindings as standaard te gebruik. Resultate:
Vir hierdie studie is 108 sputummonsters ingesluit. Vanuit die 84.3% maligne (n=91)
en 15.7% benigne (n=17) gevalle, bevestig deur ‘n diagnostiese prosedure, het
sputumsitologie ‘n sensitiwiteit van 38.5% (35/91 maligne gevalle) en ‘n spesifisiteit
van 100.0% (17/17 benigne gevalle), getoon. Geoutomatiseerde sifting het ‘n beter
sensitiwiteit met 94.3% (33/35 maligne gevalle), terwyl nie-geoutomatiseerde
(ondersoek) ‘n sensitiwiteit van 74.3% (26/35 maligne gevalle) wanneer met die finale
resultaat vergelyk, gevind.
Individuele parameters met ‘n betekenisvolle assosiasie het die teenwoordigheid van
‘n endobrongiale tumor, gedeeltelike lugwegobstruksie / stenose, ronde massa, ‘n
spekuleerde massa (negatiewe assosiasie), gewigsverlies (negatiewe assosiasie) en
plaveiselkarsinoom as die histologiese subtipe, ingesluit. Geskiktheid van die
monster was nie so betekenisvol as wat in die hipotese gestel is nie: aangesien
85.3% van ware positief gediagnoseerde sputummonsters, maar ook 65.5% van die
vals negatiewe sputummonsters, groot hoeveelhede alveolêre makrofae ingesluit het.
Gevolgtrekking:
Sputumsitologie bly steeds ‘n belangrike deel van die siftingsprogram vir
bronguskarsinoom in die openbare gesondheidssektor in Suid-Afrika. Resultate van
hierdie studie bevestig dat sputumsitologie baie spesifiek is en dat geoutomatiseerde
sifting die sensitiwiteit verbeter. Ge-outomatiseerde sifting het bewys dat dit meer
tydsbesparend is, met ‘n 83.1% vermindering (p<0.0001) in die siftingstyd wat deur
een sitotegnoloog per geval bestee word.
Resultate het bevestig dat die hoeveelheid alveolêre makrofae nie direk
proporsioneel verwant is tot die patologie nie. Hoe meer verteenwoordigend die
sputummonster was, hoe groter was die kanse om ‘n akkurate positiewe diagnose te
maak. Die assosiasie van die geskiktheid van die sputummonster en die positiewe
resultate het egter nie ‘n statisties betekenisvolle resultaat getoon nie.
Aanbevelings vir hierdie studie sluit in die aanwending van geoutomatiseerde
sputumondersoeke.
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