RIG was often or always accessible for 100% (n = 5) of respondent

RIG was often or always accessible for 100% (n = 5) of respondents in the Middle East and North Africa; 94% (n = 17) in Australia and South and West Pacific Islands; 20% (n = 1) in Tropical South America; and 56% (n = 5) in Eastern Europe and Northern Asia. Ninety-one percent (n = 158) of all respondents reported that RV was often or always see more accessible. For all regions, 35% (n = 58) and 26% (n = 43) of respondents felt that the cost was too high for RIG and RV, respectively. The availability of RV and RIG varied by geographic region. All travelers should be informed that RIG and RV might not be

readily available at their destination and that travel health and medical evacuation insurance should be considered prior to departure. Travelers should be educated to avoid animal exposures; to clean all animal bites, licks, and scratches thoroughly with soap and water; and to seek medical care immediately, even if overseas. Rabies is an acute, progressive, Natural Product Library nearly universally fatal encephalomyelitis caused by neurotropic viruses (family Rhabdoviridae, genus Lyssavirus); transmission usually occurs through the bite from a rabid mammal. While rabies has one of the highest case-fatality ratios of any infectious disease, it is highly preventable

with appropriate postexposure prophylaxis (PEP), which includes thorough wound washing and timely infiltration with rabies immune globulin (RIG) and administration of a series of rabies vaccine (RV) doses. An accurate rate of possible rabies exposures in travelers has not been calculated, although a recent study estimated from PEP records that 0.4% (range 0.01%–2.3%) of travelers receive an at-risk bite per month residence in a rabies-endemic country.[1] Canine rabies-endemic countries (ie, Africa, Asia, and parts of the Americas)

Cediranib (AZD2171) remain the highest risk to most travelers.[2] Health care providers advising travelers pre-travel to rabies-endemic areas might recommend rabies preexposure vaccination for certain travelers engaging in activities that may increase contact with wildlife (particularly bats) or staying in country for extended periods of time. However, even in industrialized countries, periodic supply limitations of RV can influence prioritization for preexposure vaccination. During periods of limited RV supply in the United States (eg, during 2008–2009), travelers who want or need preexposure vaccination may be assigned lower priority to ensure adequate vaccine for PEP and persons with high-risk occupational exposures (ie, rabies diagnostic laboratory workers).[3] Currently, only human RIG (HRIG) products are licensed in the United States. While HRIG is the preferred product for PEP, it is expensive and typically in chronic limited supply, especially in nonindustrialized countries with the highest rabies burden. Equine RIG (ERIG) is used worldwide and is available in both purified and unpurified forms.

However, the increasing use of insulin analogues poses a challeng

However, the increasing use of insulin analogues poses a challenge because commercially available insulin assays detect these with varying accuracy and precision. Insulin analogues are increasingly used in diabetes management and the case outlined here highlights the variations in assay. Initially, the local assay (ELISA kit – Dako, Copenhagen) failed to detect a significant concentration of insulin (<6pmol/L; range 9.6–65.4pmol/L) which an external reference laboratory Palbociclib clinical trial subsequently detected using the Mercodia Iso-insulin two-site

immunoassay (Uppsala, Sweden). The key analytical point is the recognition that different immunoassays detect insulin analogues to varying degrees. Clinical teams need to consider this if such cases are to be recognised. Following recent media reports where surreptitious insulin administration may be implicated in inpatient mortality, this knowledge is crucial to empower us to learn more accurately diagnose all cases of unexplained hypoglycaemia. Copyright © 2013 John Wiley & Sons. Practical Diabetes 2013; 30(3): 118–120 “
“The evolution of diabetes centres in the UK, with co-location of clinical

teams, has resulted in examples of success in improving clinical efficiency, communication and patient-centred care. “
“Erectile dysfunction (ED) is expected to affect 322 million men by 2025. A number of lifestyle factors such as smoking, obesity, alcohol consumption and lack of physical activity are linked with erectile dysfunction. We reviewed the evidence in

recent studies examining the impact of weight loss upon erectile function in obese men with and without diabetes. Esposito et al. showed that weight loss through diet and increased physical activity can improve sexual function in about one-third of obese non-diabetic men with ED. Subsequently, Dallal et al. reported that the amount of surgical weight loss after gastric bypass predicted the degree of improvement in sexual function independent of improvement in glycaemic control. Wing et al. reported Glutathione peroxidase that weight loss in older obese diabetic subjects in the Look AHEAD trial may help in preventing the worsening of ED over time. Most recently in 2011, Khoo et al. have shown that rapid diet-induced weight loss improves sexual and endothelial function and systemic inflammation in obese diabetic men. In conclusion, the majority of recent studies show that weight loss can improve erectile function in obese men, though the beneficial effect is less profound in diabetic men. Copyright © 2012 John Wiley & Sons. “
“It is a myth that screening of type 2 diabetes is ‘a given’, that we provide adequate education for patients and that increasing physical activity by simply referring patients to a health trainer can prevent type 2 diabetes. Research in this area is often seen as an easy or soft option.

Data were gathered through semi-structured, face-to-face intervie

Data were gathered through semi-structured, face-to-face interviews with 21 patients. Severity of symptoms and insistence of family and friends were the main triggers to seek professional advice from GPs and NHS 24; no patients reported seeking community pharmacy advice. Several instances of delayed GP appointments were reported, possibly click here resulting in later hospital admission. There was a lack of access to professional support available in community pharmacies. Self-care is a continuum of care from completely independent self-care with patients assuming total responsibility for their health to supported self-care, involving

the clinical judgement of health professionals.1 A number of United Kingdom government initiatives have promoted self-care and community pharmacy supported self-care to enhance access to treatment and advice, and reduce National Health Service direct and indirect costs. There is some evidence that patients inappropriately consult their general practitioners (GPs) rather than adopt self-care approaches or seek community pharmacy advice for colds and coughs.1 However, there is a lack of research on self-care

strategies adopted by those admitted to hospital with infective episodes. The aim of this study was to explore the patient pathway leading to hospital this website admission due to an infective episode, with focus on self-care strategies. Patients admitted to the infection or acute medicine admission units of a major Scottish teaching hospital, and commenced antibiotic therapy post-admission aminophylline were included. Exclusion criteria were: <16 years; no capacity to consent; and insufficient command of English. A draft semi-structured interview schedule was developed, reviewed, piloted in two patients and modified accordingly. The finalised schedule focused on: symptoms prior to admission; self-care strategies; triggers for seeking professional advice; and reflections on any professional advice prior to admission. Participants were identified by medical staff and informed consent obtained. Face-to-face interviews lasting around 15 minutes were audio-recorded and transcribed

verbatim. All transcripts were checked for accuracy prior to thematic analysis, with the coding frame constructed independently by two researchers and agreed by consensus. Data generation for 5 weeks took place during November – December 2012. The study was approved by the university and local NHS ethics committees. Twenty-one patients were invited to participate and all consented to interview. Eighteen transcripts were suitable for analysis (interview recording quality was poor for two patients, one patient was unfit for interview). Mean patient age was 56 years (standard deviation 20.9); eight were female; 11 were prescribed an antibiotic prior to admission; the most common diagnoses were skin and soft tissue infection (n = 9) and respiratory infections (n = 6). Severity of symptoms (e.

Candida species, like many other microorganisms, may colonize DUW

Candida species, like many other microorganisms, may colonize DUWL, grow into a polymicrobial biofilm and disseminate

in the water following detachment of sessile yeasts. Candida albicans and Candida parapsilosis have been isolated in the water from DUWL with other microorganisms commonly found in the human oral cavity (Witt & Hart, 1990; Walker et al., 2000; Szymanska, 2005; Castiglia et al., 2008). Thus, Candida yeasts mixed with traces of MK-1775 cell line saliva may be present in water and aerosols produced by dental handpieces. As saliva could allow fungal survival in water and biofilm already present on the surface of the lines, we investigated the survival ability of C. albicans (ATCC 3153), Candida glabrata (IHEM 9556) and C. parapsilosis (ATCC 22019) in tap water containing buy Daporinad different concentrations of saliva. Whole unstimulated saliva was collected on ice from 11 healthy adult volunteers who gently rinsed their mouth

with water before sampling to decrease bacterial contamination. Saliva was then pooled, filtered through a 0.45-μm membrane and stored at −80 °C until use. Partial characterization of pooled saliva showed that the concentrations of total proteins and d-glucose were 0.78 and 0.02 g L−1, respectively. Yeasts were cultured on Sabouraud dextrose agar plates at 27 °C for 48 h; a yeast suspension (5 × 104 cells mL−1) was incubated in tap water at 27 °C for 360 h with saliva concentrations of 1%, 5% or 20% (v/v). Tap water displayed a chlorine concentration < 0.04 mg L−1 (diethyl-p-phenyldiamine method), which would be too Silibinin low to affect yeast survival. The pH of tap water with or without saliva ranged between 7.7 (saliva 0%, 1% or 5%) and 7.6 (saliva 20%). Candida albicans and C. parapsilosis were observed only as yeast forms throughout the study, mycelial forms never being produced. In addition, we did not observe C. albicans chlamydospores. Yeast viability was evaluated during the time course

of the experiment: each yeast suspension was diluted (1 : 100 and 1 : 1000) in fresh tap water and then 100 μL was plated in duplicate on Sabouraud dextrose agar containing chloramphenicol. Each experiment was carried out at least twice on different days. Yeast CFU were enumerated after 48 h at 27 °C. Finally, the nonparametric Kruskal–Wallis test was conducted using stata 9.2 to determine statistical differences between groups. Our results showed that C. parapsilosis yeasts incubated in tap water without saliva were maintained at about 4 log(10) CFU mL−1 until 360 h of incubation (Fig. 1a). This species was less fragile than both C. albicans and C. glabrata as its inoculum remained stable throughout the experiment (Fig. 1b and c). This could be explained by the differences in the normal living environment of the studied species: C. parapsilosis is certainly less protected on the skin than C. glabrata and C. albicans in the mucosal environment and therefore could have developed a better ability to withstand severe conditions.

After the growth proceeded to opacity, an aliquot was removed and

After the growth proceeded to opacity, an aliquot was removed and used as an inoculum in a new bottle with fresh medium and an additional 5% ethanol for another 12-h incubation. The cultures were diluted and spread on agar plates without ethanol. Individual colonies, visible after 8–10 h, were subcultured in medium supplemented with 10% ethanol to confirm the ethanol tolerance of the strains. The strains were purified by repeatedly isolating single colonies in agar plates at least five times. The type strains of A. flavithermus DSM 2641T, Anoxybacillus pushchinoensis DSM 12423T and Anoxybacillus kestanbolensis NCIMB 13971T were obtained from the Deutsche Sammlung von Mikroorganismen

learn more und Zellkulturen (DSMZ). Anoxybacillus eryuanensis KCTC 13720T and Anoxybacillus tengchongensis KCTC 13721T were acquired from the Korean Collection for Type Cultures (KCTC). The cells were initially cultured overnight in LB medium with 4% ethanol. The culture was washed

twice in unsupplemented medium to remove ethanol and then used for inoculation of medium with ethanol added at concentrations Selleckchem Protease Inhibitor Library of 0–10%. The cultures were incubated without shaking at temperatures in the range of 45–65 °C for 60 h. Samples for measurement were withdrawn directly from the sealed bottles with sterile syringes before and after incubation. Growth was measured spectrophotometrically at 600 nm. To evaluate whether this organism can metabolize ethanol, ethanol was analyzed by Agilent 7890A GC System equipped with an Agilent 7694E Headspace Sampler (Agilent Technologies). The microbial biofilm and its formation were observed by light microscopy (Olympus, BX51). Sterile glass slides were placed in LB culture supplemented with 13% ethanol. The culture was incubated without shaking at 60 °C for 24 h. The slides were then taken out of the bottles and washed

three times with H2O. The remaining cells were fixed with methanol for 10 min and stained with 2% (w/v) crystal violet for 5 min. Physiological and biochemical tests were carried out without ethanol addition at 60 °C. Conventional biochemical tests were performed according to standard methods (Smibert & Krieg, 1994). Anaerobic growth experiments were carried out in Hungate tubes. The ability to utilize Olopatadine different carbon source was examined in basal medium (Pikuta et al., 2000). To minimize the effects of growth temperature and different media on bacterial fatty acid composition, all strains were uniformly incubated at 60 °C for 24 h on agar LB medium. Then, the analysis of cellular fatty acid methyl esters were performed according to the method described in the Sherlock Microbial Identification System manual (version4.0, MIDI). The final extracts were analyzed by GC/MS in scan mode, using an Agilent 7890 GC/5975 MSD system (Agilent Technologies).

The specificity of the assays developed has been tested successfu

The specificity of the assays developed has been tested successfully on 111 Fusarium isolates from different geographical origins. The detection limits for F. avenaceum/F. tricinctum esyn1

genotype and F. poae genotype were 19 and 0.3 pg, respectively. The application of the assays developed on asymptomatic wheat grain samples revealed significant positive correlations between the enniatins levels and the amount of F. avenaceum/F. tricinctum esyn1 genotype (R=0.61) and F. poae esyn1 genotype (R=0.42). Necrotrophic fungi of the genus Fusarium are common cereal pathogens worldwide. They cause seedling blight, crown rot, foot rot and head blight that may affect PLX3397 in vivo grain yield and quality (Leslie & Summerell, 2006). Head blight often results in the accumulation of various mycotoxins in the grain that is determined, to a large extent, by climatic conditions and Carfilzomib solubility dmso the potential of the fungi to produce mycotoxins (Desjardins, 2006). Enniatins (cyclic hexadepsipeptides) are a group of mycotoxins contaminating grain and grain-based products, especially in northern Europe (Jestoi et al., 2009). They have antimicrobial, insecticidal and phytotoxic activities (Gaumann et al., 1950, 1960; Grove & Pople, 1980;

Herrmann et al., 1996), and their high cytotoxicity on mammalian cells has been reported in in vitro experiments (Macchia et al., 1995; Kamyar et al., 2004; Ivanova et al., 2006). Among Fusarium Head Blight (FHB) agents of cereals, Fusarium avenaceum, Fusarium tricinctum and Fusarium poae are the most potent enniatins producers, although F. avenaceum is considered to be the major source of this group of mycotoxins in naturally contaminated grain (Logrieco et al., 2002; Jestoi et al., 2004a, b). This species is a plant pathogen over a range of climatic

zones, although usually a predominant FHB agent in colder areas (Bottalico & Perrone, 2002; Uhlig et al., 2007). Fusarium tricinctum is considered to be a weak plant pathogen, although several studies have reported Farnesyltransferase its high prevalence in the grain mycobiota of cereals under certain environmental conditions (Bottalico & Perrone, 2002). This species is closely related to F. avenaceum, and the production of enniatins by isolates of F. tricinctum has been confirmed in in vitro analysis (Herrmann et al., 1996; Logrieco et al., 2002). Fusarium poae has been identified recently as the major FHB component of wheat in Hungary, Ireland, the United Kingdom (Xu et al., 2005) and Poland (Łukanowski & Sadowski, 2002). Fusarium poae DNA determined with a TaqMan assay has also been recognized to correlate with enniatins in Finnish barley grain samples (Yli-Mattila et al., 2008). Various mycotoxin genotyping assays have been developed for the rapid detection of genes responsible for mycotoxin synthesis both from fungal culture and from plant material.

The diagnosis and treatment of genital infections in any individu

The diagnosis and treatment of genital infections in any individual have clear benefits in terms of both individual morbidity and possible infectivity to any sexual partner. In pregnancy, the welfare of the baby is an additional issue. However, apart from the recommendation that all pregnant women should be screened for HIV, HBV and syphilis, asymptomatic HIV-uninfected pregnant women in the UK are not routinely screened for genital infections. In HIV-positive pregnant women, additional considerations are the potential effects of the presence of a genital infection on MTCT of HIV-1. This could occur through

an increase in the HIV-1 VL in the genital tract and/or Selleck GPCR Compound Library the presence of chorioamnionitis. In addition, certain infections may be linked to premature birth, an event that occurs more frequently in HIV-positive women when compared with HIV-uninfected women. VL in cervicovaginal specimens has been shown to correlate with HIV-1 MTCT [6]. Genital tract VL will usually mirror the plasma VL [7], but there is increasing evidence of compartmentalization of HIV-1 between the plasma and genital tract. Genital tract HIV-1 has been detected in women with an undetectable plasma VL [[8],[9]] and genetic diversity of virus from the two compartments has been reported [10]. A number of factors

may be responsible for this, including differential drug penetration into body compartments and the presence of http://www.selleckchem.com/products/Metformin-hydrochloride(Glucophage).html genital tract infections. With increasing numbers of women in the UK aiming for and achieving a vaginal delivery an increasing number of fetuses are exposed to the cervicovaginal

secretions of HIV-positive women. The clinical significance of this is not clear. Data from the UK and Ireland [2] and France [11] showing no difference in MTCT associated with mode of delivery in women with an undetectable VL provide some reassurance that potential discordance may not be clinically relevant but further research is Methamphetamine warranted. It has long been recognized that genital infections, in particular ulcerative diseases, are associated with an increased risk of sexual transmission of HIV [[12],[13]]. This may be a consequence of an increase in local HIV replication resulting in a higher VL in genital secretions, secondary to the presence of specific microorganisms, and/or ulceration and inflammation [[14],[15]]. Organisms associated with bacterial vaginosis (BV) have been shown to stimulate HIV expression in vitro [[16],[17]]. A study from Kenya demonstrated a reduction in cervical mucosal shedding of HIV-1 RNA following treatment of both gonococcal and chlamydial cervicitis [18]. A study from Zimbabwe has shown a correlation between herpes simplex virus type 2 (HSV-2) antibody status and HIV-1 MTCT [19]. A study from Thailand of perinatal cervicovaginal lavages showed that HSV-2 shedding was associated with increased risk of intrapartum HIV transmission and that the effect was independent of perinatal cervicovaginal lavage and plasma HIV VL.

Only 47% of our travelers were VFRs compared with 27% of travele

Only 4.7% of our travelers were VFRs compared with 27% of travelers Anti-infection Compound Library high throughput overall reported in the United Nations World Tourism Organization data.[1] VFR travelers generally have contact with local populations, a longer duration of travel, use local health facilities, and have greater risks of infections.[13] In addition, we may have underestimated the number of infections given the incubation period of both HBV and HCV can be prolonged. We were unable to perform HCV PCR testing on the entire cohort of travelers

and thus some infections in the “window period of testing” may have been missed. This study nevertheless confirms that travelers to endemic countries are at risk of both HCV and HBV infection. Access to travel advice, HBV vaccination where applicable, and education regarding the modes of HBV and HCV transmission are necessary for travelers to endemic countries. We acknowledge S. Bowden, Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria 3051, Australia for performing the HCV PCRs. This HDAC inhibitor work was supported by an unrestricted research grant by GlaxoSmithKline. D. F. J., I. R., E.

M., L. E. S., D. C., and M. L. G. have no conflict of interest. K. L. and J. T. have received grant funding from GSK for an unrelated project and travel expenses to attend international travel conferences. “
“Background. To address the lack of understanding in malaria prevention among Chinese international travelers, we have conducted knowledge, attitudes, and practices (KAP) study in five different Chinese geographic areas. This survey represents one part of the background information needed to analyze imported malaria. Methods. Standardized questionnaires were distributed to Chinese international FER travelers in departure lounges at international

airports in Guangzhou, Beijing, Shanghai, Qingdao, and Nanjing. The data were entered into the Epidata 3.1 (Jens M. Lauritsen, Odense, Denmark) and analyzed by the SPSS 12.0 statistical package (SPSS Inc., Chicago, IL, USA). Results. Overall 2,495 completed questionnaires were collected from departing Chinese passengers; 1,573 were contributed by travelers who were going to malaria risk countries. More than half of all travelers spent less than 7 days to organize their trip abroad. Pre-travel medical advice was sought by 998 travelers (40.0%), 65.1% of them did so for 1–7 days before departure. Only 4.0% travelers received their knowledge from travel health providers. Among 389 travelers who were going to high malaria risk countries, only 18.0% realized that there is a high malaria risk in sub-Saharan Africa. Most travelers going to risk areas knew about personal protection measures against mosquito bites, but only 21.4% and 12.1% carried mosquito repellents or insecticides, respectively. Only 18.7% of the 1,573 potentially exposed travelers carried malaria tablets, all of them for self-treatment, none for prophylaxis. Conclusion.

The investigation and management of which has slowly evolved over

The investigation and management of which has slowly evolved over the last two decades, necessitating a rethink of diagnostic criteria. The Children’s Arthritis and Rheumatology Research Alliance (CARRA) and the United Kingdom Juvenile DM Cohort are leading

data generators in this field, supplemented in this issue of the Journal Linsitinib by two smaller cohorts of JDM from the diverse APLAR region.[1, 2] Prasad et al.[1] from India and Gowdie et al.[2] from Australia report a prevalence of muscle weakness, Gottron’s papules, and heliotrope rash not so greatly different from the initial 1975 descriptions by Bohan and Peter,[3, 4] and very similar to the 2011 description of European and Latin American patients with JDM,[5] in spite of different time period and sociocultural diversities. This two cohorts provide useful insights into the diverse clinical manifestations over and above those currently used for diagnostic classification, and both emphasise dysphagia and dysphonia. Disease manifestations may change between early and late childhood, with the UK JDM cohort reporting that children with disease onset before age 5 years were more likely to present with oedema and ulcerative skin disease.[6]

this website Gowdie et al.[2] found nail fold changes in 68% of their cohort unlike the finding of reduced nailfold capillary density virtually in all JDM patients in a longitudinal study by Schmeling et al.[7] Although capillaroscopic change seems to be a marker of both skin and muscle disease activity,[8] and has been suggested as a diagnostic criterion, it requires

further refinement and precision to become a clinically useful tool in JDM.[9] The dreadful complication of calcinosis cutis occurs in 20% to 40% of cases and more so with increasing disease duration.[10, 11] Delayed or inadequate therapy and persistent skin inflammation are thought to be predisposing factors.[12] None of the children in the Australian series [2] had calcinosis at diagnosis, though 18% had developed this probably in the Amrubicin more chronic phase. The Indian series[1] had 27% of their children with calcinosis at presentation or during follow up, which has been reported by other Indian studies, and is higher than reports from other countries [13] possibly due to a delayed diagnosis and initiation of treatment, thereby a higher cumulative period of active disease and accrual of damage. Indeed, the median duration of symptoms prior to diagnosis in the Indian study was 9.25 months [1] as compared to 2.8 months in the Australian report [2] and 5 months in the cohort of 384 children of United states pooled from 55 paediatric rheumatology clinics.[13] The factors influencing the variation in time to diagnosis and initiation of therapy which favourably impacts on both mortality and morbidity warrant further study.

Possible reasons include: younger GPs may be less confident at pr

Possible reasons include: younger GPs may be less confident at prescribing without referring to guidelines, and increasing mobile technology availability coupled with relatively high uptake of these devices by younger GPs may facilitate information seeking behaviour by using apps. Limitations arising from distributing the survey electronically predominantly included self-selection of GPs who (i) favour the use of electronic devices and

(ii) are interested in the topic. We are now developing and evaluating an antimicrobial app for GPs. 1. World Health Organization. The evolving threat of antimicrobial BMS354825 resistance.Options for action. Geneva: World Health Organization; 2012. 2. Department of Health. UK Five Year Antimicrobial Resistance Strategy 2013 to 2018. London: Department of Health; 2013. M. Wilcocka, G. Hardingb aRoyal Cornwall Hospitals NHS Trust, Truro, UK, bPeninsula College of Medicine and Dentistry, Exeter, UK Focus groups were convened to explore community pharmacists’; perception of their profession’s future.

Overarching concern PLX3397 concentration expressed was the limitations for development by being tied to the existing dispensing role. Community pharmacy needs to be valued for the support it can offer for medicines use. There is continuing discussion around expanding the role of community pharmacists with various policy documents highlighting pharmacy’s potential.1,2 As community pharmacists will have a significant role to play in the future development of their profession, we sought their beliefs and expectations of how pharmacy would evolve over the next five years. A convenience sample of

community pharmacists across Cornwall was invited to attend one of two focus groups held in early and late 2013. A total of 13 self selected community pharmacists from a range of employment backgrounds participated. Using a topic guide, proceedings Sorafenib ic50 were audio recorded, transcribed and with contemporaneous notes formed the basis for a thematic analysis. We deemed ethics committee approval was not required because we were evaluating a service. Five major themes were identified. How pharmacists think they are perceived by others: Perceptions ranged from the negative – being considered an unskilled practitioner, perhaps reflecting pharmacy’s lack of success in promoting its services, to the view of an increasingly positive public’s perception of pharmacy. How pharmacists themselves perceived their role: Although some believed they were perceived primarily as commercial retailers rather than health professionals, their self-perception was altogether more realistic – reflecting their knowledge and skills base.