HIV-1 persists to be a major health problem worldwide. A prophylactic or therapeutic vaccine offers the best hope to restrain the HIV-1 epidemic, however a consistent correlate of immune protection is yet to be found. HLA class I expression and their restricting HIV-1 specific CD8+ T cell responses have been shown to play a vital role in the control of HIV-1 infection. The interactions between HIV-1 and CD8⁺ T cell responses are complex and the mechanisms involved in the success or failure to control viraemia remain uncertain. Thus, the aim of these studies was to help define what CD8+ T cell responses a vaccine needs to induce to achieve durable immune control of HIV-1 infection. Focusing initially on HLA-B*35, an allele that has consistently been associated with rapid HIV-1 disease progression in the context of B clade infection, this study shows substantial differences in markers of HIV-1 disease outcome associated with different HLA-B*35 subtypes. Preliminary data suggest that effective targeting of a single epitope in Gag may be associated with HLA-B*35 mediated control of HIV-1 disease progression. Increased breadth of the Gag- specific CD8⁺ T cell responses is found to be associated with decreasing viral loads. These data therefore support the Gag hypothesis, and suggest that targeting of certain regions of the HIV-1 genome may have a positive effect in disease outcome, even for individuals carrying “detrimental” alleles. The extensive diversity of the HIV-1 genome and rapid viral adaptation are the main chal- lenges to vaccine design. Previous studies have suggested that effective CD8⁺ T cell responses drive selection of escape mutations that reduce viral replication capacity (VRC). There is also evidence that certain escape mutations can be transmitted from one host to another allow- ing for its accumulation in a population. The second study looked at the impact of HLA driven evolution of HIV-1 in VRC at a population level. This study compared two ART-naïve HIV-1 B clade infected cohorts, in Mexico and Barbados, in which protective HLA alleles (HLA- B*27/57/58:01/81:01) are expressed at 10% and 35% respectively, to analyze differences in VRC at a population level. Viral loads (VL) were found to be significantly higher in Mexico compared to Barbados and median CD4⁺ T cell counts significantly lower. Analysis of VRC in a subset of subjects in each cohort matched by CD4⁺ T cell counts between 300-500 cells/μl revealed that VL and VRC was significantly higher in the Mexican subset. This VRC difference was associated with accumulations in Barbados of eight previously described Gag escape mutation where fitness cost has previously been implicated. Accumulation remained significant in mismatched subjects. These data suggest that VLs and disease progression rates may differ between distinct populations as a result of the frequency of protective alleles in the respective populations, and that CD4⁺ T cell count-based guidelines to initiate antiretroviral therapy (ART) may need to be modified accordingly, to optimize the effectiveness of treatment-for-prevention strategies and reduce HIV-1 transmission rates to the absolute minimum. The final project aimed to improve the HIV-1 replication fitness assays currently used in the context of C clade infection. In order to achieve this, we attempted to design a clade C infectious molecular clone for the testing of gal-pol gene regions. However, the clones produced were not replication competent. Sequence analysis showed a large quantity of stop codons, most located within env which may explain the lack of infectivity. Chapter 5 describes the methodology used in the construction of the clade C isolate and suggests future work. Although we were unsuccessful in producing a replication competent virus, the construction of a C clade backbone which replicates efficiently remain an aim due to its importance for research directed to the analysis of genetic determinants of C clade virus. Data presented in this thesis suggest that vaccine-induced immune responses should aim to focus on vulnerable regions of the virus. These are conserved regions that can not escape without a high fitness cost and with a complex and difficult selection of compensatory mutations. Although much work remains to be done to achieve an effective CD8⁺ T cell based vaccine, hope remains that the induction of HIV control may be possible.

In vitro fertilization treatments are responsible for 1-5% births in industrialized countries. The safest way to generate a pregnancy is to transfer a single embryo to the mother, reducing the likelihood of multiple gestations. Hence, in order to maximize the chance of success, it is extremely important that the embryo prioritised for transfer is the most capable within the cohort of embryos generated by the patient. Along with cytogenetic components, it has been suggested that embryo protein expression patterns may correlate with its ability to implant. However, embryo proteomics strategies have not been easy to harness mainly due to the complexity of the media the embryos are cultured in, and the low concentration of the proteins that are secreted. In this study, the use of the blastocentesis procedure, which allows the safe retrieval of embryo inner fluid (blastosol), was described. The use of the blasocoel fluid as a source of embryonic DNA for preimplantation genetic assessment was also investigated. From this highly purified embryonic sample, a comprehensive catalogue of proteins present in the human blastosol was generated using standard and custom- made mass spectrometry strategies. The embryonic origin of these proteins was validated by gene expression microarray and RNASeq analysis. These experiments also allowed the identification of differentially expressed genes in the first two cell lineages, the Inner Cell Mass and the Trophectoderm. Finally, a targeted proteomics strategy able to measure part of the previously described protein targets in single blastosol samples was employed. The correlation between the presence and abundance of proteins of interest in single blastosols and several biological characteristics of the embryo, including its chromosomal status, was assessed. These data are of major interest for the understanding of human embryo development. The validated embryo-derived protein catalogue and blastocyst gene expression profiles generated in this study, provides access to a thorough document for consultation in human embryology proteomics-based experiment design, paving the way to next-generation proteomic-based embryo assessment.

MicroRNAs (miRNAs) have now been identified in a vast array of organisms and a great deal of research has been carried out to elucidate the role they play. The dysregulation of miRNA expression has been implicated in a number of disease states and their importance has been highlighted by the beginning of their utilisation as therapeutics. The focus of this study was to identify the role played by miRNAs encoded by the Marek’s disease vaccine viruses, Marek’s disease virus serotype 2 (MDV-2) and Herpesvirus of turkeys (HVT). In order to better understand the functions of these miRNAs we wanted to identify their targets within the host cell. Using a combination of bioinformatic and biochemical approaches we were able to build up a library of potential targets. Three viral miRNA targets; AKT3, RAP1A and DEK, were further validated using dual-luciferase assays to highlight the exact site of miRNA targeting, and western blots to demonstrate an effect of miRNA targeting on protein abundance. An attempt at using label-free proteomics to observe the viral miRNA mediated changes in the host proteome is also described, however this proved to be unsuccessful. Additionally the function of one particular MDV-2 miRNA, mdv2-miR-M21, was explored in more detail, describing its role as a potential ortholog of the host miRNA; gga-miR-29b. By using the observation that the viral miRNA contained an identical 'seed' region to the host miRNA, we were able to use the data collected from existing studies on miR-29b to search for targets of mdv2-miR-M21. We demonstrated that mdv2-miR-M21 targeted DNMT3B, crucial for epigenetic modification of the genome. The final part of this study aimed to understand the wider context the viral miRNAs played in the viral biology and protective ability of the vaccine viruses. The miRNAs were deleted from the viruses, and then the miRNA-deletion viruses were used to vaccinate birds before challenge with the oncogenic Marek's disease virus serotype 1 (MDV-1), survival rates to the 'wild-type' MDV-2 and HVT vaccine viruses were then compared.

Sammanfattning: Bakgrund: Den vanligaste drogen i Sverige är alkohol. Idag uppskattas att drygt 780 000 människor lever med ett alkoholmissbruk eller beroende. Kostnaden för det svenska samhället är upp till 150 miljarder kronor under ett års tid. Det finns olika faktorer som gör att ett alkoholmissbruk kan utvecklas hos en människa och dessa har oftast ett samband. Överallt i olika vårdinstanser kommer sjuksköterskan att möta patienter som har alkoholrelaterade problem. Det finns en problematik kring mötet med dessa patienter. De svårigheter som kan uppstå är att sjuksköterskor stigmatiserar och har en negativ inställning till patienter med alkoholmissbruk på grund av både fördomar och okunskap. Ett behov av fördjupad kunskap är nödvändigt för att sjuksköterskor ska kunna bemöta denna patientgrupp på ett bättre sätt. Syfte: Syftet med studien var att beskriva sjuksköterskors erfarenheter av att möta patienter med alkoholmissbruk. Metod: En litteraturstudie där innehållsanalysen utgick från en sammanställning av Graneheim och Lundman. Resultatet baseras på tio stycken vetenskapliga original artiklar. Resultat: I resultatet framkom det tre huvudkategorier innehållande underkategorier: Betydelsen av att vara väl förberedd, Att hantera sina egna känslor och Att anpassa omvårdnaden. Betydelsen av att vara väl förberedd innehåller två stycken underkategorier som är Kunskap och Erfarenhet. Att hantera sina egna känslor innehåller tre stycken underkategorier som är Stress, oro och frustration, Rädsla och otrygghet samt Stigmatiserande syn. Den sista kategorin Att anpassa omvårdnaden innehåller två stycken underkategorier som är Samtalets betydelse och Att hitta strategier. Slutsats: Kunskap och erfarenhet visade sig vara viktigast för att kunna bemöta patienter med alkoholmissbruk.

Bakgrund: Magnetresonanstomografi (MRI) har med sin bildkvalitet och detaljrikedom börjat bli ett alternativ till ultraljud som idag är ledande inom fosterdiagnostik. Tidigare forskning har studerat magnetfältets inverkan på fostret, denna inverkan har fortfarande inte kunnat bekräftas. Syfte: Syftet är att svara på evidensfrågan: Vad finns det för evidens för att MR-undersökningar på gravida kvinnor leder till fosterskada? Metod: Arbetet är en systematisk litteraturstudie som innehåller 13 vetenskapliga artiklar, som har sökts fram via olika databaser. Resultat: Ingen evidens för biologiska effekter eller hörselnedsättning kunde ses hos exponerade foster, dock gavs motstridiga resultat gällande gadolinium och värmeökning. Gadolinium kan ge NSF biverkningar och ökad risk för missfall. Värmeökning kan ske hos fostret om normal mode inte används och längre sekvenser körs. Det är osäkert vem av fostret och modern som uppnår högsta helkropps-SAR värdet. Slutsats: Resultatet av denna studie skall bejakas med försiktighet då resultaten visar olika och få studier har gjorts med högsta evidensvärdet. Alla 13 studier i detta arbete påpekar att mer forskning bör göras för att kunna säkerställa riskerna med MR på gravida.

No description available.

Schizophrenia is primarily treated with the use of antipsychotic medications. However, antipsychotics used have severe, dose-dependent side effects in schizophrenia patients. Therefore, there is a need for new adjunctive drugs that lower the effective dose of first line schizophrenia drugs and improve patient symptoms. Neuroinflammation is associated with microglial activation in schizophrenia, and increased tumor necrosis factor-alpha (TNF) has shown to be associated with Metabolic Syndrome in schizophrenia patients. A newly developed anti-neuroinflammatory, PD2024, reduces TNF-alpha action in vitro and in vivo, and has been shown to be well-tolerated in rat and dog studies with no adverse effects. The purpose of this research is to evaluate the effect of PD2024 in two well-defined schizophrenia models in rats. The neonatal quinpirole model has been established through administration of the dopamine D2-like agonist quinpirole (NQ) or saline control (NS) postnatally from days 1-21. NQ treatment results in increases of dopamine D2 receptor sensitivity throughout the animal’s lifetime without changing receptor number, mimicking a hallmark of schizophrenia. The polyinosinic:polycytidylic acid (Poly I:C) model is based on mimicking an increase immune response during early brain development, which has been shown to increase the prevalence of schizophrenia. Poly I:C (2 mg/kg) was administered during the neonatal period at postnatal days (P)5-7 to produce this effect. Both models were given PD2024 at 10mg/kg orally through the diet from P30-67. Prepulse inhibition (PPI) was used to test sensorimotor gating deficits in the rats. PPI has past research showing its use as a quantitative phenotype for evaluating schizophrenia-associated behavioral and neurobiological deficits. In our PPI test, rats are exposed to three different, randomly ordered noise trials. The trials included a pulse trial with a 120-decibel startle pulse, a prepulse trial with an auditory click at 73, 76, or 82-decibels, and a no stimulus trial without any additional noise. The rats were given 25 randomized trials, comprised of 5 pulse, 15 prepulse (5 each of 73, 76, and 82dB) and 5 no stimulus trials. Background noise was 70dB, and the rats were tested during adolescence (days 45-46) and adulthood (60-65). In NQ adolescent rats, PPI was significantly improved in the PD2024-treated compared to NQ controls. NQ-PD2024 and NS rats were statistically equivalent throughout the trials. These results were reflected in the NQ adult model as well. The Poly I:C adolescents treated with PD2024 also demonstrated improved PPI performance compared to Poly I:C controls. This improvement was also shown in the adult Poly I:C rats. Overall, the PPI deficits in both models improved between 15 to 30% in adolescence and adulthood. These results indicate that PD2024 is effective in treating schizophrenia-associated behaviors.

Bakgrund: Ateroskleros är den främsta bakomliggande orsaken till att människor avlider i hjärt- och kärlsjukdomar. Karaktäristiskt för ateroskleros är att plack uppkommer som en följd av LDL-retention i blodkärlens väggar, vilket sätter igång en inflammation. Cyklodextrin har visat sig vara bra på att ta upp kolesterol samt transportera läkemedel. Det är därför intressant att undersöka dess potentiella möjlighet att behandla ateroskleros. Syfte: Studiens syfte är att undersöka om cyklodextrin-derivat kan användas för direkt behandling av ateroskleros och indirekt som en del av en nanopartikels-behandling. Metod: En systematisk litteraturstudie genomfördes där sju artiklar från PubMed mellan 2015 och 2020 studerades. Studierna var utförda på ApoE-knockoutmöss. Sökorden var; Cyclodextrin, atherosclerosis, cholesterol, inflammation och plaque. Resultat: Alla studier visade minskad plackbildning. Två cyklodextrin-derivat minskade dock inte plackbildning. De studier som undersökte kolesterolkristallisering visade att det minskade. Studierna som använde nanopartiklar visade att antalet makrofager minskade och att kollageninnehållet ökade, vilket inte sågs i studierna som använde cyklodextrin-derivat. Proinflammatoriska markörer minskade både i studierna som använde nanopartiklar och de som använde cyklodextrin-derivat.      Slutsats: Cyklodextrin-derivaten och nanopartiklarna påverkade faktorer positivt utifrån ett behandlingsperspektiv. Dock går det inte att säga vilken klinisk relevans förändringarna hade. Fler studier är nödvändiga för att förstå vilken klinisk betydelse dessa förändringarna har.

Introduction Bihar ranks among the most socio-economically disadvantaged states in India, and its public health system had long suffered from structural deficiencies which contributed to poor health outcomes. In November 2013, the Bihar government, with funding from Gates Foundation and technical support from CARE India, launched the state-wide Bihar Technical Support Program (BTSP) – seeking to address gaps in infrastructure, supply chain, and human resources, as well as the quality of service delivery, so as to improve reproductive, maternal, newborn and child health (RMNCH) and nutrition service provision. BTSP adopted a two-pronged strategy – conducting (i) periodic comprehensive facility assessments (CFAs) to identify and address the structural gaps; and (ii) nurse-mentoring programs to develop competency among nursing cadres in providing basic and comprehensive emergency obstetric and newborn care (BEmONC/ CEmONC) services. Through three inter-linked papers, the dissertation aimed to conduct an evidence-based assessment of this health system strengthening program. “Facility readiness” (structural readiness of public health facilities) was operationalized in terms of infrastructure, essential supplies, and human resources, while “facility performance” was operationalized based on the direct observation of normal vaginal deliveries and newborn care (including management of immediate complications if needed) and infection prevention practices in the labor rooms. The first paper describes the evolution of BTSP, and examines the initial progress made in facility readiness between 2015 and 2016. The second paper: (i) conducts a comparative assessment of facility readiness between 2017 (at end of the first four years of BTSP) and 2019, and describes the continuation of progress or lack thereof; (ii) quantifies facility readiness through a scoring system that reflects the readiness to provide maternal and newborn care (MNC) services; and (3) compares the change in this score over time (2015, 2017 and 2019) across different districts and levels of health facilities in Bihar. Thus, the first and second papers together examine the extent to which Bihar’s public health facilities were structurally strengthened in terms of physical infrastructure, supplies and workforce by utilizing data from all four rounds of CFAs conducted till date. The third paper asks the next logical question in a health system strengthening process – was facility readiness positively and significantly associated with facility performance? This is an important query, as it aims to provide evidence of synergistic progress, as envisioned under BTSP. First, the paper examines whether the facility-level performance changed, by comparing baseline (May-December, 2018) and endline (October-December, 2019) assessment data from the nurse-mentoring program (locally called AMANAT Jyoti). Second, it assesses the association of facility readiness (based on CFA 2019 data) with endline facility performance in providing MNC services. Methods The first paper utilizes a structured, narrative review of scientific and grey literature to describe evolution of the BTSP since 2014, based on programmatic learnings through prior years (2011-2013) of collaborative vertical interventions. Subsequently, the paper measures the tangible change in select facility-level characteristics, utilizing quantitative data generated through two rounds of CFAs conducted by CARE India in 2015 (n=534 facilities) and 2016 (n=550 facilities). The second paper utilizes quantitative data generated through two rounds of CFAs conducted by CARE India in 2017 (n=550 facilities) and 2019 (n=552 facilities). Each CFAs covered all Level 2 (primary health centers) and Level 3 (higher-level facilities) public health facilities in Bihar that conducted at least 100 deliveries in the preceding year. Subsequently, the paper constructs a “facility-level MNC structural readiness score” – henceforth referred to as facility readiness score, based on a common set of indicators from CFA 2015, 2017 and 2019, to reflect human resources, infrastructure and essential supplies related to delivering MNC services. The paper uses this score to map the change at 2-year intervals, from 2015 to 2019, at both facility and district levels. The third paper utilizes quantitative data generated through two separate assessments conducted by CARE India – the 2019 CFA, and the 2018-2019 assessment of AMANAT Jyoti (nurse-mentoring program), which involved direct observation of normal vaginal deliveries, newborn care, and infection prevention practices in the labor rooms. The paper constructs baseline and endline facility-level MNC performance scores – henceforth referred to as facility performance scores based on data from AMANAT Jyoti assessments, and examines the association between endline facility performance and facility readiness scores. While descriptive statistics was used to present findings from the CFAs and AMANAT Jyoti assessments, paired t tests were used to test the mean change in scores over time and between the different levels of facilities. The association between endline facility performance and facility readiness scores was tested using simple as well as multiple linear and multinomial logistic regression modelling. Results With a demonstrated intent to improve the ailing public health sector, the Bihar government in 2010 forged a collaboration with Gates Foundation to accelerate progress across RMNCH and nutrition programs. Through the Integrated Family Health Initiative program (IFHI, 2011-2013), outreach-based and facility-based solutions were implemented in eight programmatically-prioritized districts to address the stated goals. However, over this period, it became apparent that long-term success of such initiatives remained critically dependent on strengthening the foundational components of Bihar’s public health system –physical infrastructure, supply chain for drugs, consumables and equipment, and the skilled health workforce. These programmatic learnings motivated a re-think and consequent state-wide launch of the BTSP – characterized by a novel structure of health governance that was deeply embedded within the public health system, and a robust information management system that could generate, analyze and disseminate data on community- and facility-level services to support decision making. The quantitative analyses of CFA data (in first and second papers) provided an assessment of the changes that happened at the level of health facilities, likely supported by the policy-level modifications. There was a clear sense of prioritization of the limited resources – with constant focus on structurally preparing health facilities to deliver basic MNC services, more so at Level 2 (primary health centers). By 2019, at least 99% facilities at either level provided 24x7 delivery services and had designated labor rooms, 97% had designated newborn care corners which were mostly located inside the labor rooms, 70% or more had at least one functional fetal doppler, baby weighing machine, radiant warmer, and AMBU bag with neonatal oxygen masks. The improvement in availability of essential supplies like oxytocin, misoprostol, magnesium sulphate, antibiotics, and reproductive health commodities (condoms, intrauterine contraceptive devices, sanitary napkins, iron-folic acid tablets, contraceptive pills) were particularly notable during the 2017 and 2019 CFAs. However, the supply chain variably faltered for a number of other essential supplies like oral rehydration solutions, functional oxygen cylinders, normal saline and ringer lactate solutions. The data revealed that facility-level inefficiencies in utilizing the electronic inventory management system to accurately reflect actual status of supplies within the facility, likely compromised procurement and distribution. With regards to human resources, while a large number of auxiliary and general nurse midwives were available for service during CFA 2019, the BTSP faced continuing challenges (2015-2019) in recruiting and/or retaining physicians, especially the specialist physician cadres. By CFA 2019, these structural changes were also supported by remarkable improvements in two related services areas –availability of emergency transport, and laboratory services. The comparison of facility readiness scores (second paper) based on CFA 2015, 2017 and 2019 showed that while the mean scores increased sharply for both Level 2 (increase=1.51 (95% confidence interval: 1.39, 1.63)) and Level 3 (1.39 (1.1, 1.69)) facilities between 2015 and 2017, the progress was less pronounced at both levels between 2017 and 2019. 25 of the 38 districts in Bihar demonstrated a continuous increase in mean scores over the 3 CFAs. As for the remaining 13 districts, their 2019 mean scores remained higher than that during 2015. The analysis of AMANAT Jyoti assessment data (third paper) revealed improvements across 36 (80%) of the 45 performance parameters assessed through direct observation of deliveries between the baseline and endline. However, at least 80% compliance was observed for only 11 of 45 (24%) assessed parameters at baseline, and 16 of 45 (36%) at endline. The mean facility performance score increased significantly among both types and levels of facilities – but the increase was higher among Level 3 (mean increase = 1.56, p=0.0005, n=13) and CEmONC (1.82, p=0.0029, n=9) facilities, than among Level 2 (0.32, p =0.0288, n=121) and BEmONC (0.33, p=0.0168, n=125) facilities. The regression analysis failed to identify any linear relationship between facility readiness and performance scores. However, a significant positive association was observed between facility readiness score and the middle tertile of endline facility performance score (vs. lowest tertile as reference) in multiple multinomial logistic regression modeling (n=132 facilities). With increasing facility readiness score, the odds of a facility being in the middle tertile of the endline facility performance score relative to the lowest tertile was 1.68 (95% CI = 1.02, 2.76), after controlling for baseline facility performance score, mean delivery volume, and the facility level. Conclusion The BTSP can be best described as a diagonal health system strengthening initiative –one that starts with a focus on specific programmatic (RMNCH) outcomes, but strives to achieve these through identifying and addressing bottlenecks across the health system. The efforts made to revamp health governance through creating structures for technical support from the state- to block-levels is particularly laudable, as is the remarkable capacity building in collecting and using facility-level data to inform programs and policies. The dissertation identified that BTSP has made appreciable progress in structurally preparing Bihar’s public health facilities to deliver basic MNC services – with improvements in related infrastructure, essential supplies, and supportive services like referral transport and laboratory facilities, as well as through recruitment of large number of ANM and GNM nurses. However, the process encountered a number of challenges, and it may be worthwhile to adopt a targeted approach to address some of these concerns. For example, it is important that the BTSP works to equip all facilities with electronic inventory management systems, while simultaneously training the personnel using such systems. To circumvent the chronic shortage of specialist physicians, a “task shifting” approach may help maximize utilization of existing health workforce to strengthen service delivery capacity. Further, the overall level of facility performance of MNC service delivery remained low at endline despite improvement from the baseline scores, and there was limited evidence of a significant positive association between facility readiness and performance scores. As these scores reflect the minimum essential requirements for a MNC service delivery setting, the BTSP clearly has challenges ahead. They must continue to address the persistent challenges in facility readiness and facility performance so that these two facility-level interventions will complement each other and influence outcomes. As the onus of this diagonal health system strengthening program incrementally shifts from development partners to the government, it will be important to recognize the significance and complexity of this effort.

Background: Diagnostic accuracy and reliability of acquired apraxia of speech (AOS) in the presence of co-occurring aphasia and/or dysarthria is crucial for appropriate treatment selection and clinical decision making. However, overlapping symptomology and lack of operationalization of AOS assessment methods have contributed to inadequate interrater reliability of perceptual measures differentially diagnostic of AOS. Purpose: This study investigated factors influencing the operationalization of AOS assessment methods, primarily interrater reliability of perceptual characteristics of differentially diagnostic (i.e., phonetic and prosodic errors) measures in order to inform assessment methods in AOS with concomitant aphasia. In addition, several other factors influencing the operationalization of AOS assessment methods were explored including: the utility of a pre-existing stimulus readily available in a standardized aphasia assessment (WAB-R), interrater reliability of non-discriminatory characteristics of AOS (i.e., auditory groping and false starts), the influence of alternating motion rates (AMRs) and sequential motion rates (SMRs) on a diagnosis of AOS, and the influence of the WAB-R subtests on error production by diagnostic group. Methods: Forty participants presenting with varying aphasia subtypes and severities and potential motor speech impairment were included. Speech production errors were analyzed by four raters using narrow transcription methods in response to the WAB-R spoken language subtest stimuli (Naming, Repetition, and Spontaneous Speech subtests) of the WAB-R. Interrater reliability of perceptual measurement of both differentially diagnostic and non-discriminatory features of AOS when using consistent stimuli (WAB-R), measures (Apraxia of Speech Rating Scale) and trained raters using narrow transcription methods were examined. In addition, percentage agreement of AOS diagnoses with and without the inclusion of AMRs/SMRs, as well as the influence of WAB-R subtest on error production across groups with AOS with concomitant aphasia and those with aphasia only were also examined. Results: Both differentially diagnostic as well as non-discriminatory speech characteristics were shown to demonstrate adequate interrater reliability across a variety of aphasia subtypes and severities of both AOS and aphasia. Adequate agreement between a diagnosis of AOS with and without the inclusion of AMRs/SMRs was reported as well as a lack of significant differences of phonetic and prosodic error production between subtests. Conclusion: The current work provides preliminary evidence of adequate interrater reliability of perceptual features of AOS using consistent stimuli (WAB-R), measures (Apraxia of Speech Rating Scale), and trained raters using narrow transcription. Findings from this work also support the inclusion of the AMRs/SMRs in AOS assessment and highlight the importance of their role when assessing individuals with borderline/mild motor speech impairments. These preliminary results support the consistency and operationalization of assessment methods through the investigation of reliability of perceptual measurements of differentially diagnostic characteristics of AOS in the presence of aphasia.