Use of blood colour for assessment of arterial oxygen saturation in immobilized impala (Aepyceros melampus).

OBJECTIVE: To determine the relationship between arterial blood colour [as defined by the International Commission on Illumination (CIE) L∗a∗b∗ colour space] and haemoglobin oxygen saturation [functional saturation (SaO2) and fractional saturation (FO2Hb)], and if arterial blood colour can be used to predict arterial haemoglobin oxygen saturation. STUDY DESIGN: Descriptive study as an adjunct to two prospective randomized crossover studies. ANIMALS: A group of 10 wild caught adult female impala (Aepyceros melampus) weighing 34.1 ± 5.2 kg (mean ± standard deviation). METHODS: Impala were immobilized with potent opioids (0.09 mg kg-1 of etorphine or thiafentanil). A total of 163 arterial blood samples were collected anaerobically into heparinized syringes from arterial cannulae and analysed immediately using spectrocolourimetry and co-oximetry. Data were analysed by modelling the relationship between predicted arterial blood colour CIE L∗a∗b∗ components and SaO2 and FO2Hb. The models were then used to predict values for L∗, a∗ and b∗ to produce a colour palette for the range of SaO2 and FO2Hb used. The modified version of the Farnsworth-Munsell hue test was used to assess the subjective ordering of the resulting colour palette by 20 observers. RESULTS: The second-order polynomial (quadratic) model produced the best fit for all three arterial blood colour CIE L∗a∗b∗ components for both SaO2 and FO2Hb. The regression models were used to generate predicted arterial blood colour CIE L∗a∗b∗ components for the midpoint of each decile over a range of SaO2 and FO2Hb percentages (15% to 95%). The resulting colour palettes were correctly ordered by all observers in the SaO2 range of 45-95% saturation. CONCLUSIONS AND CLINICAL RELEVANCE: An association between arterial blood colour (as defined by CIE L∗a∗b∗ components) and SaO2 and FO2Hb exists, and arterial blood colour can be used to give a clinically useful estimate of arterial haemoglobin oxygen saturation in impala.

Clinical diagnosis of sensory neuropathy in HIV patients treated with tenofovir: A 6-month follow-up study.

BACKGROUND: Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV-infection and its treatment. However, data on the incidence of SN in neuropathy-free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. AIMS: We investigated the 6-month incidence of SN in ART naïve individuals initiating tenofovir (TDF)-based cART, and the clinical factors associated with the development of SN. METHODS: 120 neuropathy-free and ART naïve individuals initiating cART at a single center in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every 2-months for a period of ~6-months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin-prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above). RESULTS: A total of 88% of the cohort completed three visits within the 6-month period. The 6-month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80-210) at an incidence rate of 0.37 (95% CI: 0.2-0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (P < .05). INTERPRETATION: We found that within the first 6 months of starting cART, incident SN persists in the post-stavudine era, with 11 (9%) of individuals developing asymptomatic SN, and 9 (8%) developing symptomatic SN.

Psychological Factors Associated With Painful Versus Non-Painful HIV-Associated Sensory Neuropathy.

HIV-associated sensory neuropathy (HIV-SN) is a common, and frequently painful complication of HIV, but factors that determine the presence of pain are unresolved. We investigated: (i) if psychological factors associated with painful (n = 125) versus non-painful HIV-SN (n = 72), and (ii) if pain and psychological factors affected quality of life (QoL). We assessed anxiety and depression using the Hopkins Symptoms Checklist-25. Pain catastrophizing and QoL were assessed using the Pain Catastrophizing Scale and Euroqol-5D, respectively. Presence of neuropathy was detected using the Brief Neuropathy Screening Tool, and pain was characterised using the Wisconsin Brief Pain Questionnaire. Overall, there was a high burden of pain, depression and anxiety in the cohort. None of the psychological variables associated with having painful HIV-SN. Greater depressive symptoms and presence of pain were independently associated with lower QoL. In those participants with painful HIV-SN, greater depressive symptom scores were associated with increased pain intensity. In conclusion, in a cohort with high background levels of psychological dysfunction, psychological factors do not predict the presence of pain, but both depression and presence of pain are associated with poor quality of life.

Polymorphisms in CAMKK2 may predict sensory neuropathy in African HIV patients.

HIV-associated sensory neuropathy (HIV-SN) is the most common neurological condition associated with HIV. HIV-SN has characteristics of an inflammatory pathology caused by the virus itself and/or by antiretroviral treatment (ART). Here, we assess the impact of single-nucleotide polymorphisms (SNPs) in a cluster of three genes that affect inflammation and neuronal repair: P2X7R, P2X4R and CAMKK2. HIV-SN status was assessed using the Brief Peripheral Neuropathy Screening tool, with SN defined by bilateral symptoms and signs. Forty-five SNPs in P2X7R, P2X4R and CAMKK2 were genotyped using TaqMan fluorescent probes, in DNA samples from 153 HIV(+) black Southern African patients exposed to stavudine. Haplotypes were derived using the fastPHASE algorithm, and SNP genotypes and haplotypes associated with HIV-SN were identified. Optimal logistic regression models included demographics (age and height), with SNPs (model p < 0.0001; R (2) = 0.19) or haplotypes (model p < 0.0001; R (2) = 0.18, n = 137 excluding patients carrying CAMKK2 haplotypes perfectly associated with SN). Overall, CAMKK2 exhibited the strongest associations with HIV-SN, with two SNPs and six haplotypes predicting SN status in black Southern Africans. This gene warrants further study.

Progression of pain in ambulatory HIV-positive South Africans.

Cross-sectional studies report that pain in ambulatory HIV-infected individuals is frequent and often undermanaged. Expanding access to HIV treatment in developing countries means that infected individuals are living longer, but there is a dearth of pain-directed studies from developing countries that describe the progression of pain and its treatment over any period of time. The aim of this study was to characterize the progression of pain and its treatment over a 6-month period in 92 ambulatory HIV-positive patients attending an outpatient clinic in Johannesburg, South Africa. We used the Wisconsin Brief Pain Questionnaire to assess changes in pain intensity, pain sites, pain interference, and pain treatment. At visit 1, pain was present in 78 of 92 patients (85%). Of the 78 patients with pain, 67 had moderate or severe pain (86%) and pain affected two or more body sites simultaneously in 57 of these patients (73%). After 6 months, pain prevalence still was high, but had fallen to 50 patients (54%). Of the patients with pain at visit 2, the proportion with moderate or severe pain (82%), or two or more pain sites (62%) had decreased. Analgesic use was low at both time points (5% and 25% analgesic use at visit 1 and 2, respectively). Despite the high pain burden, pain interference in daily activities was very low across the period assessed. The burden of pain in this cohort of ambulatory HIV-positive patients was high, but there were significant reductions in pain burden over time.

Social media as a tool to understand the distribution and ecology of elusive mammals.

Comparatively little is known about the distribution and ecology of Aardvark (Orycteropus afer) and Temminck's Ground Pangolin (Smutsia temminckii). Both are elusive species that are normally nocturnal, solitary, and fossorial. Formally collected records have been used to map the distribution of these species, and social media records provide a tool to gather information on their distribution and ecology. We obtained 680 photographs and videos of aardvarks and 790 of ground pangolins in southern Africa from publicly available posts on Facebook and Instagram (2010-2019). The images provide new insights into the distribution, activity, drinking, and predation-and confirm that aardvarks are more diurnally active when they are in poor body condition. Social media can provide useful supplementary information for understanding of elusive mammals. These "soft" data can be applied to other species.

Chronic pain is no more prevalent in people living with HIV than in their uninfected counterparts in South Africa.

BACKGROUND: There are few studies on chronic pain prevalence in people living with HIV, and there are no studies comparing chronic pain prevalence in an HIV-infected group (HIV+) to that found in an uninfected group (HIV-) in the same population. This study was undertaken to (1) estimate the chronic pain prevalence in HIV+ individuals and (2) compare chronic pain prevalence between HIV+ and HIV- groups in a population. METHODS: Individuals ≥15 years old were recruited using multi-stage probability sampling in the 2016 South African Demographic and Health Survey. In an interview, participants were asked whether they currently had pain or discomfort, and if so, whether that pain or discomfort had persisted for at least 3 months (operational definition of chronic pain). Blood samples were taken from a volunteering sub-sample for HIV testing. RESULTS: A total of 6584 of 12,717 eligible individuals answered the questionnaire and were tested for HIV. Mean age: 39.1 years (95% confidence interval [CI]: 38.3-39.9), per cent female: 55% (95% CI: 52-56) and tested HIV+: 19% (95% CI: 17-20). The prevalence of chronic pain was 19% (95% CI: 16-23) in the HIV+ group, which was similar to that found in the HIV- group (20% [95% CI: 18-22]; odds ratio [adjusted for age, sex, socio-economic status] = 0.93 [95% CI: 0.74-1.17], p-value = 0.549). CONCLUSION: The prevalence of chronic pain in South Africans living with HIV was approximately 20%, and having HIV was not associated with an increased risk of chronic pain. SIGNIFICANCE: Using data from a large, national, population-based study in South Africa, I show for the first time that the prevalence of chronic pain in that population did not differ materially between the part of the population that was living with HIV compared with their uninfected counterparts (both approximately 20%). These findings run counter to the dogma that there is a greater risk of having pain in people living with HIV.

Temminck pangolins relax the precision of body temperature regulation when resources are scarce in a semi-arid environment.

Climate change is impacting mammals both directly (for example, through increased heat) and indirectly (for example, through altered food resources). Understanding the physiological and behavioural responses of mammals in already hot and dry environments to fluctuations in the climate and food availability allows for a better understanding of how they will cope with a rapidly changing climate. We measured the body temperature of seven Temminck's pangolins (Smutsia temminckii) in the semi-arid Kalahari for periods of between 4 months and 2 years. Pangolins regulated body temperature within a narrow range (34-36°C) over the 24-h cycle when food (and hence water, obtained from their prey) was abundant. When food resources were scarce, body temperature was regulated less precisely, 24-h minimum body temperatures were lower and the pangolins became more diurnally active, particularly during winter when prey was least available. The shift toward diurnal activity exposed pangolins to higher environmental heat loads, resulting in higher 24-h maximum body temperatures. Biologging of body temperature to detect heterothermy, or estimating food abundance (using pitfall trapping to monitor ant and termite availability), therefore provide tools to assess the welfare of this elusive but threatened mammal. Although the physiological and behavioural responses of pangolins buffered them against food scarcity during our study, whether this flexibility will be sufficient to allow them to cope with further reductions in food availability likely with climate change is unknown.

A Systematic Review and Meta-analysis of Non-pharmacological Methods to Manipulate Experimentally Induced Secondary Hypersensitivity.

This systematic review and meta-analysis investigated the effects of non-pharmacological manipulations on experimentally induced secondary hypersensitivity in pain-free humans. We investigated the magnitude (change/difference in follow-up ratings from pre-manipulation ratings) of secondary hypersensitivity (primary outcome), and surface area of secondary hypersensitivity (secondary outcome), in 27 studies representing 847 participants. Risk of bias assessment concluded most studies (23 of 27) had an unclear or high risk of performance and detection bias. Further, 2 (of 27) studies had a high risk of measurement bias. Datasets were pooled by the method of manipulation and outcome. The magnitude of secondary hypersensitivity was decreased by diverting attention, anodal transcranial direct current stimulation, or emotional disclosure; increased by directing attention toward the induction site, nicotine deprivation, or negative suggestion; and unaffected by cathodal transcranial direct current stimulation or thermal change. Area of secondary hypersensitivity was decreased by anodal transcranial direct current stimulation, emotional disclosure, cognitive behavioral therapy, hyperbaric oxygen therapy, placebo analgesia, or spinal manipulation; increased by directing attention to the induction site, nicotine deprivation, or sleep disruption (in males only); and unaffected by cathodal transcranial direct current stimulation, thermal change, acupuncture, or electroacupuncture. Meta-analytical pooling was only appropriate for studies that used transcranial direct current stimulation or hyperbaric oxygen therapy, given the high clinical heterogeneity among the studies and unavailability of data. The evidence base for this question remains small. We discuss opportunities to improve methodological rigor including manipulation checks, structured blinding strategies, control conditions or time points, and public sharing of raw data. PERSPECTIVE: We described the effects of several non-pharmacological manipulations on experimentally induced secondary hypersensitivity in humans. By shedding light on the potential for non-pharmacological therapies to influence secondary hypersensitivity, it provides a foundation for the development and testing of targeted therapies for secondary hypersensitivity.

Pathogenesis of HIV-associated sensory neuropathy: evidence from in vivo and in vitro experimental models.

HIV-associated sensory neuropathy (HIV-SN) is a frequent neurological complication of HIV infection and its treatment with some antiretroviral drugs. We review the pathogenesis of the viral- and drug-induced causes of the neuropathy, and its primary symptom, pain, based on evidence from in vivo and in vitro models of HIV-SN. Viral coat proteins mediate nerve fibre damage and hypernociception through direct and indirect mechanisms. Direct interactions between viral proteins and nerve fibres dominate axonal pathology, while somal pathology is dominated by indirect mechanisms that occur secondary to virus-mediated activation of glia and macrophage infiltration into the dorsal root ganglia. The treatment-induced neuropathy and resulting hypernociception arise primarily from drug-induced mitochondrial dysfunction, but the sequence of events initiated by the mitochondrial dysfunction that leads to the nerve fibre damage and dysfunction are still unclear. Overall, the models that have been developed to study the pathogenesis of HIV-SN, and hypernociception associated with the neuropathy, are reasonable models and have provided useful insights into the pathogenesis of HIV-SN. As new models are developed they may ultimately lead to identification of therapeutic targets for the prevention or treatment of this common neurological complication of HIV infection.

HIV-associated sensory neuropathy: risk factors and genetics.

HIV-associated sensory neuropathy (HIV-SN) remains a common neurological complication of HIV infection despite the introduction of effective antiretroviral therapies. Exposure to neurotoxic antiretroviral drugs and increasing age have consistently been identified as risk factors for HIV-SN, while comorbid conditions with underlying predisposition to cause peripheral neuropathy (eg, diabetes mellitus, malnutrition, isoniazid exposure), ethnicity, and increasing height also have been implicated. Genetic association studies have identified genes affecting mitochondrial function and genes involved in the inflammatory response that modify the risk for HIV-SN among patients exposed to neurotoxic antiretrovirals. However, there is a lack of data on clinical, demographic, and genetic risk factors for HIV-SN in the modern era, with the rate of HIV-SN remaining unacceptably high despite the introduction of safer medications. Thus, more work is required to identify the principal factors that increase an individual's risk for HIV-SN so that effective preventative or therapeutic strategies can be implemented.

Greater baseline pain inclusion criteria in clinical trials increase regression to the mean effect: a modelling study.

ABSTRACT: We modelled the effects of pain intensity inclusion thresholds (3/10, 4/10, and 5/10 on a 0- to 10-point numerical pain rating scale) on the magnitude of the regression to the mean effect under conditions that were consistent with the sample mean and variance, and intermeasurement correlation observed in clinical trials for the management of chronic pain. All data were modelled on a hypothetical placebo control group. We found a progressive increase in the mean pain intensity as the pain inclusion threshold increased, but this increase was not uniform, having an increasing effect on baseline measurements compared with study endpoint measurements as the threshold was increased. That is, the regression to the mean effect was magnified by increasing inclusion thresholds. Furthermore, the effect increasing pain inclusion thresholds had on the regression to the mean effect was increased by decreasing sample mean values at baseline and intermeasurement correlations, and increasing sample variance. At its smallest, the regression to the mean effect was 0.13/10 (95% confidence interval: 0.03/10-0.24/10; threshold: 3/10, baseline mean pain: 6.5/10, SD: 1.6/10, and correlation: 0.44), and at its greatest, it was 0.78/10 (95% confidence interval: 0.63/10-0.94/10; threshold: 5/10, baseline mean pain: 6/10, SD: 1.8/10, and correlation: 0.19). We have shown that using pain inclusion thresholds in clinical trials drives progressively larger regression to the mean effects. We believe that a threshold of 3/10 offers the best compromise between maintaining assay sensitivity (the goal of thresholds) and the size of the regression to the mean effect.

South African men and women living with HIV have similar distributions of pain sites.

BACKGROUND: No studies have investigated sex differences in the location and number of pain sites in people living with human immunodeficiency virus (HIV) (PLWH), despite evidence that women, in general, bear a greater burden of pain than men. AIM: To determine sex differences in the location and number of pain sites, and whether there were demographic or disease-related differences in the number of pain sites. SETTING: South African tertiary hospital HIV clinics and a community healthcare centreMethods: We conducted a retrospective analysis of records from South African PLWH who had pain. RESULTS: Of the 596 participant records, 19% were male (115/596) and the median number of pain sites for both sexes was 2 (interquartile range [IQR]: 1 to 3). Pain was most frequently experienced in the head (men: 12%, women: 38%), feet and ankles (men: 42%, women: 28%), abdomen (men = 19%, women = 28%) and chest (men = 20%, women = 20%). After correcting for multiple comparisons, males were less likely to experience headache than females (Fisher's exact text, odds ratio [OR] = 0.23, 95% confidence interval [CI]: 0.12 - 0.42, p = 0.000). Pain at other body sites was experienced similarly between the sexes. There was no meaningful variation in the number of pain sites between the sexes (logistic regression, p = 0.157). CONCLUSION: A similar location and number of pain sites were experienced by male and female South African PLWH. The locations of pain sites were different from previous reports, however, suggesting that research into pain in PLWH cannot necessarily be generalised across cultures.

Importance of testing the internal consistency and construct validity of the Pittsburgh Sleep Quality Index (PSQI) in study groups of day and night shift workers: Example of a sample of long-haul truck drivers in South Africa.

Irregular work times promote inconsistent completion of the Pittsburgh Sleep Quality Index (PSQI) among shift workers. We aimed to demonstrate the importance of testing the internal consistency and construct validity of the PSQI and of the Epworth Sleepiness Scale (ESS) by presenting the methodology in a sample of long-haul truckers in South Africa. Internal consistency of the questionnaires was assessed by Cronbach's alpha (defined as raw alpha≥0.70), and construct validity by factor analysis. 302 participants (49.3%) reported at least one night shift/week. Overall, the PSQI and ESS's alpha were 0.42 and 0.85, respectively. The factors explained 19.6% of 57.0% of the variance. The PSQI's alpha was 0.46 in night shift workers and 0.38 in non-night shift workers. In this occupational group, the PSQI must be used with caution. Testing the internal consistency and construct validity among the assessed population seems necessary. Sleep questionnaires adapted to shift workers should be preferred.

Minimum daily core body temperature in western grey kangaroos decreases as summer advances: a seasonal pattern, or a direct response to water, heat or energy supply?

Using implanted temperature loggers, we measured core body temperature in nine western grey kangaroos every 5 min for 24 to 98 days in spring and summer. Body temperature was highest at night and decreased rapidly early in the morning, reaching a nadir at 10:00 h, after ambient temperature and solar radiation had begun to increase. On hotter days, the minimum morning body temperature was lower than on cooler days, decreasing from a mean of 36.2°C in the spring to 34.0°C in the summer. This effect correlated better with the time of the year than with proximate thermal stressors, suggesting that either season itself or some factor correlated with season, such as food availability, caused the change. Water saving has been proposed as a selective advantage of heterothermy in other large mammals, but in kangaroos the water savings would have been small and not required in a reserve with permanent standing water. We calculate that the lower core temperature could provide energy savings of nearly 7%. It is likely that the heterothermy that we observed on hot days results either from decreased energy intake during the dry season or from a seasonal pattern entrained in the kangaroos that presumably has been selected for because of decreased energy availability during the dry season.

High individual pain variability in people living with HIV: A graphical analysis.

BACKGROUND: People living with HIV (PLWH) frequently experience pain. Following calls to analyse individual-level data in addition to group-level data in pain studies, we compared individual and group-level changes in pain prevalence, intensity and number of pain sites over 48 weeks in a large cohort of PLWH. This is the largest ever cohort study of pain in PLWH, and is the first to report pain at the level of the individual. METHODS: Participants included all participants with complete pain records from a randomized clinical trial (RCT) for the treatment of HIV (n = 787/1053). At weeks 0, 12, 24, 36 and 48 we assessed participants' pain in the last week; presence of pain, and if present, the intensity and locations of the pain. We used standard averaging methods to describe data at the group level, and unique graphical reporting methods to analyse data at the level of the individual. RESULTS: Group-level data demonstrated a trend for pain prevalence to decline over time (19% week 0, 12% week 48). Worst pain intensity remained stable (median between 4/10 and 5/10), as did the number (median = 1) and common sites of pain across the 48 weeks. In contrast, individual-level data demonstrated high intra-individual variability with regards to the presence of pain, and the intensity and location of the pain. CONCLUSIONS: While our group-level data were similar to previous longitudinal studies, an apparent reduction in pain over 48 weeks, the individual-level data showed large variability within individuals in that same time frame. SIGNIFICANCE: This graphical analysis highlights the high variability in pain (pain prevalence, intensity and body sites) across time in people living with HIV, and how presenting averaged data hides this important variability. Our data support the reporting of individual-level data in human experimental and observational studies.

Pain in Clients Attending a South African Voluntary Counseling and Testing Center Was Frequent and Extensive But Did Not Depend on HIV Status.

BACKGROUND: The frequency of pain is reported to be high in people living with HIV, but valid comparisons between people living with HIV and HIV-negative cohorts are rare. We investigated whether HIV infection influenced frequency and characteristics of pain in adults undergoing voluntary testing for HIV. SETTING: Participants were recruited from an HIV voluntary counseling and testing center at the Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. METHODS: Pain was assessed using the Wisconsin Brief Pain Questionnaire. Depressive and anxiety symptomatology was determined using the Hopkins Symptom checklist-25. We then stratified by HIV status. RESULTS: Data from 535 black South Africans were analyzed: HIV-infected n = 70, HIV-uninfected n = 465. Overall, frequency of any current pain was high with 59% [95% confidence interval (CI): 55 to 63, n: 316/535] of participants reporting pain, with no difference related to HIV status: HIV-infected 50% (95% CI: 37 to 61, n: 35/70), HIV-uninfected 60% (95% CI: 56 to 65, n: 281/465). Pain intensity and number of pain sites were similar between the groups as were symptoms of anxiety and depression: mean Hopkins Symptom Checklist-25 1.72 (95% CI: 1.57 to 1.87) HIV-infected participants and 1.68 (95% CI: 1.63 to 1.73) HIV-uninfected participants. Univariate analysis showed female sex and greater depressive and anxiety symptomatology associated with pain. In a multivariable modeling, only depressive and anxiety symptomatology was retained in the model. CONCLUSION: The high frequency of pain found in both HIV-infected and HIV-uninfected individuals presenting at a voluntary counseling and testing center was more likely to be associated with depression and anxiety, than with the presence or absence of HIV.

Almost 1 in 5 South African adults have chronic pain: a prevalence study conducted in a large nationally representative sample.

Limited information on the prevalence and risk factors for chronic pain is available for developing countries. Therefore, we investigated the prevalence of chronic pain and the association between this pain and various personal and sociodemographic factors by including questions in the South Africa Demographic and Household Survey 2016. The survey was conducted by face-to-face interviews with a nationally representative sample of the adult population (ages 15 and older, n = 10,336). Chronic pain was defined as pain or discomfort that had been experienced all the time or on and off for 3 months or more. The prevalence of chronic pain was 18.3% (95% confidence interval [CI]: 17.0-19.7). Women were more likely than were men to have chronic pain (men = 15.8% [95% CI: 13.9-17.8]; woman = 20.1% [95% CI: 18.4-21.8]), and the prevalence of chronic pain increased from 11.3% (95% CI: 9.6-13.3) for the age range 15 to 24 years to 34.4% (95% CI: 30.6-38.4) for the age range over 65 years. The body sites affected most frequently were the limbs (43.6% [95% CI: 40.4-46.9]), followed by the back (30.5% [95% CI: 27.7-33.6]). This article presents the prevalence of chronic pain in the general population of a middle-income African country. These data give much needed insights into the burden of, and risk factors for, chronic pain in low-resource settings, and identify priority groups for intervention.