Our MRSA colonization rate of 8% is probably an underestimate giv

Our MRSA colonization rate of 8% is probably an underestimate given that we do not conduct routine surveillance among our out-patient population and those with colonization came to our attention because either they were admitted to the hospital and had a nares surveillance culture performed, or they had a clinical culture sent for other reasons. As noted, 15 (55.5%) of our 27 MRSA-colonized HIV-infected patients subsequently developed an MRSA infection during the study period, most of which were SSTIs; however, our patient population was not large enough to assess risk factors for infection among

our colonized patients. Prior antibiotic http://www.selleckchem.com/products/Dapagliflozin.html use in the past year and CD4 count <200 cells/μL were significant risk factors for MRSA colonization or infection, while use of ART in the past year was protective. Previous studies have identified prior antibiotic exposure within the past year as a risk factor for MRSA colonization or infection [11]. Beta-lactam exposure has specifically been reported as a risk for MRSA infection [5], but our study did not identify any particular class or agent conferring risk. Also, unlike previous studies, there was no protective effect of trimethoprim-sulfamethoxazole selleck prophylaxis despite 98% of our MRSA isolates being susceptible, and with over 25% of our cases

having received trimethoprim-sulfamethoxazole within a year of their documented colonization or infection. Of note, our statistical value was close to being significant (P=0.06), raising the possibility that a larger patient population may have demonstrated a protective effect of trimethoprim-sulfamethoxazole prophylaxis. There were eight multidrug-resistant MRSA isolates in our study sample. Given this small number of isolates, we could not assess predisposing factors for multidrug resistance. However, it is important to acknowledge the presence of these isolates in our population as it may affect our empiric therapy for infections, discouraging use of fluoroquinolones, clindamycin and macrolides. Consistent with previous findings, our study revealed Mannose-binding protein-associated serine protease a significant

risk of MRSA when nadir CD4 count was <200 cells/μL. This is not unexpected given that HIV-infected patients with CD4 counts <200 cells/μL are at higher risk for opportunistic infections, including bacterial infections. Thus, these patients may have more frequent, longer hospitalizations, receive more antibiotics and undergo more invasive procedures, all of which may increase the risk for MRSA acquisition [9,11]. Although hospitalization and antibiotic exposure in the year prior to infection were both included in our multivariate analyses, we did not specifically look at the frequency of clinic visits or hospitalizations, duration of hospitalizations or duration of antibiotic courses, any of which could have had an effect on our analyses.

cerevisiae is K+ efflux contributing to the maintenance of a stab

cerevisiae is K+ efflux contributing to the maintenance of a stable plasma ZD1839 supplier membrane potential (Arino et al., 2010). Information on

the activity of Tok channels in yeasts is scarce, but in C. albicans the gene has been identified, the function of the protein studied and deletion mutants characterized (Baev et al., 2003). Homozygous deletion of CaTOK1 completely abolishes the currents and gating events characteristic of the Tok1 channel. The same study also reported that mutants lacking this gene showed an increased viability after treatment with the potent salivary toxin Histatin 5, which induces the efflux of cellular ATP, potassium and magnesium (Baev et al., 2003). More recently, it has been shown that K+ efflux via CaTok1 is required for the progression of an apoptosis-like process in Candida cells. Because K+ efflux is one of the earliest events of the apoptotic process in metazoan cells and is presumed to be necessary for activating biochemical apoptotic pathways, the authors propose that the effect of channel-mediated K+ efflux on apoptosis has been evolutionary conserved among species ranging from yeasts to humans (Andres et al., 2008). Transport systems mediating the exchange of alkali–metal–cations for protons exist in the plasma membranes of probably all

organisms, and in the membranes of most eukaryotic organelles (Arino et al., 2010). Genes homologous find more to S. cerevisiae NHA1 (Na/H Antiport) have been found in all sequenced yeast genomes and members of the plasma-membrane NHA family have been so far characterized

in 10 nonconventional yeast species, c.f. below. However, in six of them, the characterization of their transport capacity and substrate specificity is purely based on data obtained upon their heterologous expression in S. cerevisiae, and only for four species (S. pombe, Z. rouxii, C. albicans and C. glabrata) this information has been complemented with phenotype and transport studies in deletion/overexpression mutants. The main substrates of the yeast antiporters are sodium and/or potassium cations, together with their analogues Ribonucleotide reductase lithium and rubidium. Members of the NHA family differ in their length (from 468 for SpSod2 to 985 amino acid residues in S. cerevisiae and C. parapsilosis antiporters) and this difference is related to the length of their C-termini. The N-termini predicted 12 transmembrane segments and connecting hydrophilic loops are highly conserved (Pribylova et al., 2006; Krauke & Sychrova, 2008). According to the number of NHA proteins in the plasma membrane and to their functional specialization, the 10 yeast species can be divided in two subgroups, one containing three members (S. pombe, Z. rouxii, Yarrowia lipolytica) in which the original NHA1 gene has been probably duplicated and the two antiporters gained differing functions (sodium detoxification and maintenance of potassium homeostasis), whereas in the larger subgroup, only one plasma-membrane antiporter with multiple functions exists.

This study was conducted between July and October 2005 among FBT

This study was conducted between July and October 2005 among FBT of Shell International and Exploration (SIEP) based in Rijswijk, The Netherlands. learn more These FBT had registered themselves previously as part of the Fitness

to Work (FtW) program for business travelers. An e-mail containing an introduction to the FtW program and the definition of a FBT had been sent to all employees (∼2,500). Using travel booking data we confirmed that this self-registration had successfully registered 97% of all FBT. A FBT was defined as an employee who met at least one of the following company-developed criteria: Travel within a region (eg, Europe) on flights of more than 4 hours, three or more times per month; or The use of adequate personal

protective measures (PPM) was defined by us as the combination of two or more measures such as covering arms and legs, using mosquito repellents, keeping windows and doors closed, using air-conditioning, mosquito nets, or insecticide spray. Appropriate anti-malarial drug regimens were defined to conform to Shell travel advice standards [based on World Health Organization (WHO),7 U.S. Centers for Disease Control and Prevention, and LCR8 (Dutch national coordination centre for traveler's Cell Cycle inhibitor health) advice]. The actual risk of contracting malaria was based on destination (countries and regions) and length of stay, and was scored as high, low, or no risk using the WHO map and details in the accompanying country list.7 Malaria risk was “indeterminate” if travelers had not indicated exact routing through countries where areas with different risks exist. The web-based questionnaire was developed

with the use of Apian Survey selleck chemicals llc Pro 3.0. With approval from ETHAB, the original survey was adapted for electronic use for this retrospective study covering the most recent travel in the preceding 2 years. A question on the incubation period of malaria was added. All 608 self-registered FBT were invited to take part in this study by a personal e-mail containing a link to the web-based questionnaire and a unique password, which ensured that each individual could enter only once. With intervals of a few weeks, non-responding employees received 2 to 3 reminders. Where appropriate, chi-square test or Fisher’s exact test was used. Continuous data were compared with t-test or Wilcoxon’s test for non-parametrical distributed numerical data. Statistical analysis was performed using a computer-assisted software package (SPSS version 12.0, SPSS Inc., Chicago, IL, USA). Results were considered statistically significant at p < 0.05. The survey was returned by 383 of the 608 self-registered FBT (63%).


“International Journal of Paediatric Dentistry 2012; 22: 2


“International Journal of Paediatric Dentistry 2012; 22: 292–301 Objectives.  The purpose of this study was to assess reliability, discriminant validity, and convergent validity of the Oral Health Impact Profile (COHIP) Korean version in a representative community sample of 8- to 15-year-old Korean children. Methods.  A Korean version of COHIP was developed according to the standard procedure of cross-cultural adaptation of self-reported instruments. A representative community sample of 2236 schoolchildren was selected by cluster sampling method. Results.  Mean age of the participants was 11.8  years. Mean and median of the

overall COHIP score were Docetaxel mw 103.3 (SD 13.3) and 106, respectively. Internal reliability and retest reliability were excellent with Chronbach’s alpha 0.88 and intraclass correlation coefficient 0.88. Face validity was confirmed with 98% of participants reporting the COHIP questionnaire was easy to answer. Nonclinical factors such 17-AAG in vitro as self-rated oral health or satisfaction with oral health were significantly related with overall

COHIP score and five subscale scores (P <  0.001) in a consistent manner. Children with carious permanent teeth and with orthodontic treatment need had highly significantly lower overall COHIP score (P < 0.01). Conclusion.  The Korean version of the COHIP was successfully developed. The internal reliability, retest reliability, face validity, discriminant validity, and convergent

validity of the COHIP Korean version were confirmed. “
“International Journal of Paediatric Dentistry 2012; 22: 244–249 Objective.  The aim of this study was to use an Arabic version of the Early Childhood Oral Health Impact Scale (ECOHIS) in a pilot study, to evaluate differences in parental perception of the oral health-related quality of life (OHRQoL) of their children below 71 months of age and assess their suitability as proxy assessors. Methods.  A translated version of the ECOHIS was administered to the parents (both fathers and mothers) of 97 children aged between Urease 2 and 6 years. The overall ECOHIS scores and the mean number of ‘don’t know’ responses between parents were compared using a paired t-test. The correlation of the ECOHIS scores to the dft was compared using a linear regression model. The reliability of the parents’ responses was compared using the Cronbach’s alpha and the intraclass correlation coefficient (ICC). Results.  Early Childhood Oral Health Impact Scale responses and their relation to the dft of the child seem to suggest that fathers have significantly less accurate knowledge of the OHRQoL of their children than mothers. Conclusion.  The concern showed by Saudi fathers does not correlate to the oral status of their child. Saudi fathers may not be apt as proxies to assess the OHRQoL of their children. “
“International Journal of Paediatric Dentistry 2012; 22: 419–426 Background.

On the day of his return to France, the second child of the famil

On the day of his return to France, the second child of the family, a 10-year-old boy, began experiencing high fever, vomiting,

and diarrhea. He was admitted to our children’s hospital in Paris, France, 5 days later. At admission he was weak and presented myalgia and generalized maculopapular rash. His temperature was 38°C. Initial laboratory tests were unremarkable; a thin blood smear for malaria was negative. Two consecutive serologies for dengue fever [PANBIO IgM and IgG Capture enzyme-linked immunosorbent assay (ELISA)] as well as NS1 Ag detection were negative at 48-hour intervals. Sirolimus clinical trial Polymerase chain reaction (PCR) detection of dengue virus was also negative, as was a third serology 10 days Olaparib after the first. The eldest brother, aged 16 years, was the last of the three siblings to have acute onset of fever, which started 48 hours after his return to France. Admitted to the hospital at the same time as his brother (case 2), he presented with high fever (39.6 °C), diarrhea, conjunctival hyperemia, myalgia, sore throat, and irritating cough. Initial laboratory tests were as follows: leukocyte

count 4,300/mm3; platelet count 132,000/mm3; hemoglobin 15.4 g/dL; SGOT 105 U/L (normal 5–45 U/L), SGPT 77 U/L (normal 5–60 U/L); C-reactive protein 40 mg/L (normal 0–10 mg/L). As was the case for his brother, a thin blood smear for malaria was negative. Three consecutive serologies for dengue fever (PANBIO IgM IKBKE and IgG Capture ELISA) were negative, as

were NS1 Ag and PCR detection. Five days after onset of the first symptoms, the patient developed a generalized maculopapular rash. The three brothers recovered fully within 2 weeks of the onset of symptoms. Initially, they presented with similar clinical features, which quite naturally led us to suspect a contagious disease. Although the first two serology tests for dengue fever were positive in the index case in Indonesia, a third one (PANBIO IgM and IgG Capture ELISA), this time in France, came back negative for both IgM and IgG. This led to the prescription of serological tests for other infectious diseases, including measles. For this latter, the tests for all three of the boys were positive (Table 1). We note that none of the siblings had been vaccinated for measles, despite national recommendations. Measles should be included in the differential diagnoses of patients presenting febrile exanthema after travel. A few years ago, chikungunya was considered the most likely cause of febrile exanthema in returning travelers.[1] However, recent measles outbreaks throughout the world have increased the risk for travelers to contract this disease. According to the GeoSentinel Surveillance Network, febrile exanthema accounts for 12% of dermatological conditions in returning travelers.[2] In a study by Caumes and colleagues in 1995, febrile exanthema was the main symptom in 4.1% of returning travelers presenting with skin diseases.

Only the simultaneous presence of psmrAB, but not the single gene

Only the simultaneous presence of psmrAB, but not the single gene alone, conferred the tolerance of E. coli KNabc to up to 0.6 M NaCl and at alkaline pH. pH-dependent Na+(Li+)/H+ antiport activity was detected from everted membrane vesicles prepared from E. coli KNabc cells carrying find more psmrAB, which had the highest activity at pH 9.0. However, a detailed

test for antimicrobial drugs showed that E. coli DH5α with psmrAB only exhibited slight resistance to chloramphenicol, but not other representative antimicrobial drugs especially ethidium bromide. Protein sequence alignment showed that neither PsmrA nor PsmrB has homology with known single-gene or multiple-gene Na+/H+ antiporters, or such proteins as TetA(L) and MdfA with Na+/H+ antiport activity. Taken together, PsmrAB should function mainly as a novel two-component Na+/H+ antiporter. This is the first example of a PSMR family member that exhibits Na+/H+ antiporter activity. In bacteria, Na+/H+ antiporters are Angiogenesis inhibitor ubiquitous secondary transporters that catalyze the efflux of intracellular alkali cations in exchange for external protons, which play a vital role in reducing the cytoplasmic concentration of toxic alkali cations

and supporting Na+(Li+)/K+-dependent intracellular pH homeostasis under alkaline conditions (Ito et al., 1999; Padan et al., 2005). Na+/H+ antiporter genes or the genes with Na+/H+ antiporter activity have been increasingly cloned and functionally identified in Escherichia coli mutants KNabc or EP432 lacking major antiporters (Padan et al., 2004). So far, Na+/H+ antiporters are sorted into two main kinds based on the number of genes: One kind of Na+/H+ antiporters are encoded by a single gene including nhaA (Karpel et al., 1988), nhaB (Pinner et al., 1992), nhaC (Nakamura et al., 1996), nhaD (Ito et al., 1997), napA (Waser et al., 1992), nhaP (Utsugi et al., 1998), nhaG (Gouda et al., 2001) and nhaH (Yang et al., 2006c). The other kind of Na+/H+ antiporters containing multiple subunits are encoded by an operon or a gene cluster such as mrp operon from Bacillus subtilis (Ito et al., 1999), mnh gene cluster from Staphylococcus aureus (Hiramatsu

et al., 1998) and pha2 gene cluster from Sinorhizobium fredii (Jiang et al., 2004; Yang et al., 2006a). Oxymatrine Moreover, an unique tetracycline/H+ antiporter TetA(L) was reported to possess Na+/H+ antiporter activity (Cheng et al., 1994). Another E. coli multidrug resistance (MDR) protein MdfA with a broad-specificity MDR phenotype (Edgar & Bibi, 1997) was also characterized to exhibit Na+(K+)/H+ antiporter activity (Lewinson et al., 2004). In our previous studies, a novel species Halobacillus dabanensis D-8T was isolated and characterized from Daban Salt Lake in Xinjiang Province, China (Liu et al., 2005), and two genes nhaH (Yang et al., 2006c) and nap (Yang et al., 2006b) were cloned from H. dabanensis and found to possess Na+/H+ antiporter activity.

’ The aim of this research was to explore the digital literacy tr

’ The aim of this research was to explore the digital literacy training experiences and needs of healthcare students and their academic teaching staff. Ethical approval was gained from all Faculty review panels; the Dean granted ‘gatekeeper’ permission. An invitation to participate in activity-based focus groups was circulated (email, newsletter) to healthcare students (nursing, midwifery, nutrition/dietetics, pharmacy, physiotherapy) and their academic teaching staff. Consent forms gathered demographic data plus an indicator of self-reported

digital literacy. Focus groups were activity-based including: defining digital literacy (post-its), sharing experiences of using and learning to use technology on a timeline of childhood-school-university-work (group rich picture), SWOT (strengths, weaknesses, opportunities, threats) analysis of inclusion of digital literacy in healthcare curricula and related staff Small molecule library training, which note-taking scribes observed. Qualitative data were analysed thematically using five-step approach (familiarisation, coding, indexing, reviewing, summarising). Four focus groups each lasting an hour were conducted: 2 with healthcare students

(n = 6; n = 7); 2 with academic teaching staff (n = 6; n = 5). The majority of student participants (n = 10) and all staff were female with pharmacy well-represented (n = 12; n = 4). All except 1 student were under 30 years old; only 2 members of staff were under 40 years old. Staff self-reported their digital literacy more highly than did students. The wealth of data captured check details in the timeline showed

the variation in technologies accessed at different stages in life and the range of formal (training course, teacher-led) and informal (self-, peer-, parent-taught) teaching and learning experienced. Key themes noted by scribes were assumptions associating age with digital literacy, variation in awareness of IT help and resources available. The quality of IT-related course provision was a recognised strength with promotion, timing/breadth of training provision perceived as weaknesses. Threats acknowledged by both staff and students related to potential impact on coursework marks, workplace preparedness and career progression, effectiveness of delivery of teaching. Opportunities identified were provision of flexible, 5-Fluoracil datasheet targeted, on-demand, multi-media resources preparing both staff and students to be more confident and effective in using IT resources for teaching and learning. Although limited to 4 focus groups, this study shows healthcare students and their academic teaching staff have varying levels of digital literacy acquired through formal and informal teaching and learning. Findings indicate digital literacy should be formally recognised in healthcare curricula with training provided for teaching staff to prepare the future healthcare workforce to make more and better use of technology. 1.

Lesions of the subthalamic nucleus or the substantia nigra reticu

Lesions of the subthalamic nucleus or the substantia nigra reticular nucleus produced only minor changes in the amount of sleep–wakefulness and did not alter sleep architecture. Finally, power spectral analysis revealed that lesions of the striatum, accumbens and GP slowed down the cortical electroencephalogram. Collectively, our results suggest that the BG, via a cortico-striato-pallidal loop, are important neural circuitry regulating sleep–wake behaviors and cortical activation. “
“Howard Hughes Medical Institutes Janelia

Farm, Ashburn, VA, USA Fast ripples (FRs) are network oscillations, defined variously as having frequencies of > 150 to > 250 Hz, with a Ku-0059436 clinical trial controversial mechanism. FRs appear to indicate a propensity of cortical tissue to originate seizures. Here, we demonstrate field oscillations, at up to 400 Hz, in spontaneously epileptic human cortical tissue in vitro, and present a network model that could explain FRs themselves, and their relation to ‘ordinary’ (slower) ripples. We performed network simulations with model pyramidal neurons, having selleck chemicals llc axons electrically coupled. Ripples (< 250 Hz) were favored when conduction of action potentials, axon to axon, was reliable. Whereas ripple population activity was periodic, firing of individual axons varied in relative

phase. A switch from ripples to FRs took place when an ectopic spike occurred in a cell coupled to another cell, itself multiply coupled to others. Propagation could then start in one direction only, a condition suitable for re-entry. The resulting oscillations were > 250 Hz, were sustained or interrupted, and had little jitter in the firing of individual axons. The form of model FR was similar to spontaneously occurring FRs in excised human epileptic tissue. In vitro, FRs were suppressed by a gap junction blocker. Our data suggest that a given network can produce ripples, FRs, or both, via gap junctions, and that FRs are favored by clusters of axonal gap junctions. If axonal gap junctions indeed occur in epileptic tissue, and are mediated by connexin 26 (recently shown to mediate coupling between

immature neocortical pyramidal cells), then this prediction is testable. “
“Input–output computations of individual neurons may be affected by the three-dimensional structure of their dendrites and by the location of input synapses on specific parts of their dendrites. fantofarone However, only a few examples exist of dendritic architecture which can be related to behaviorally relevant computations of a neuron. By combining genetic, immunohistochemical and confocal laser scanning methods this study estimates the location of the spike-initiating zone and the dendritic distribution patterns of putative synaptic inputs on an individually identified Drosophila flight motorneuron, MN5. MN5 is a monopolar neuron with > 4000 dendritic branches. The site of spike initiation was estimated by mapping sodium channel immunolabel onto geometric reconstructions of MN5.

As evident based upon the large cadres of lupus patients and grow

As evident based upon the large cadres of lupus patients and growing

numbers of lupus investigators within these Asian communities, significant advances are being made in the evaluation and care of systemic lupus erythematosus in Asian countries. Additional work in therapeutic, genetic, prognostic and biomarker work is underway and will provide more insights to the unique and common aspects of lupus pathogenesis within and across Asia, as well as the rest of the world. The authors declare no conflicts of interest. “
“To review the clinical profile of patients with plasma cell dyscrasias presenting with inflammatory arthritis. Retrospective analysis was performed on clinical, laboratory and imaging learn more data of patients who presented with

inflammatory arthritis between May 2009 and April 2010 and were subsequently diagnosed as having plasma cell dyscrasias. Six out of 630 patients presenting with inflammatory arthritis were identified. The demographic, clinical and laboratory characteristics of these patients were analyzed. The diagnosis of monoclonal gammopathy was based on protein electrophoresis, immunoelectrophoresis and bone marrow biopsy. The outcomes of the treatments were analyzed. Four patients had monoclonal gammopathy of unknown significance and two patients had multiple myeloma. Mean age of the patients was 65 years (range 59–74). Three patients presented with oligoarticular arthritis, two with symmetrical polyarticular joint pains and one with fleeting periarticular pains. Wrist and shoulder were the most commonly involved joints. Three Panobinostat mouse patients had carpal tunnel syndrome. Five

patients were seronegative for both rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Mean erythrocyte sedimentation rate (ESR) was high in all patients (range: 82–120 mm/h with a mean of 99.6 mm/h). Arthritis improved with chemotherapy in patients with multiple myeloma. Occurrence of inflammatory arthritis with plasma dyscrasias is more than a chance association. Plasma cell dyscrasias should be ruled out in any elderly patient presenting with atypical arthritis with disproportionately high ESR, high creatinine and hyperglobulinemia. “
“To describe our experience with 16 patients with eosinophilic fasciitis (EF) Digestive enzyme treated in our clinic over 14 years. We retrospectively reviewed the charts of all patients with biopsy-proven EF. We collected data regarding demographics, clinical presentations, possible triggers, labs, imaging, treatment and response to therapy on follow-up. Eight women and eight men with a mean age of 52 years were included in the study. Three patients related the onset to prior strenuous exercise and one was exposed to vibratory machinery. Fourteen patients had a gradual onset and presented with induration of the skin.

Swarming is also a type of motility that is powered by rotating h

Swarming is also a type of motility that is powered by rotating helical flagella; however, it differs from swimming in that it requires an increase in the number of flagella per cell, the secretion of surfactants to reduce surface tension and allow spreading, and in that the movement

occurs in a coordinated manner across a surface (Kearns, 2010). Because flagella are essential for both swimming and swarming, the effect of PMs on both of these motility phenotypes was tested. Figure 3a shows that PGRE, PG, and PGP, all at 10%, decreased the swimming motility of CFT073 by 50%, 14%, and 70% of the control, respectively. Figure 3b–e show representative images of CFT073 swimming under see more control, 10% PGRE, 10% PG, and 10% PGP conditions, respectively. It is noteworthy that PGP, not PGRE, was the strongest inhibitor of swimming motility. Evaluation of the swarming motility revealed that the PMs inhibited this phenotype more strongly than the swimming motility phenotype. Our results revealed that the swarming of UPEC

CFT073 was completely blocked by 10% PGRE and that 10% PG and 10% PGP reduced the motility by approximately 75% and 20%, respectively, as depicted in Fig. 4a. click here Figure 4b–e show representative images of swarming assays for control, 10% PGRE, 10% PG, and 10% PGP treatments, respectively. The fact that swarming motility is more repressed than swimming motility under equivalent concentrations of PGRE or PG may be explained by the fact that swarmer cells are hyperflagellated, but only one flagellum is required for swimming (Henrichsen, 5-Fluoracil purchase 1972; Harshey & Matsuyama, 1994; Kearns, 2010). It is therefore possible that the decrease in expression of fliC upon exposure to PMs

still allows for the synthesis of enough flagellar filaments to enable bacteria to swim, but swarming becomes prohibitive. Additionally, as mentioned above, SEM imaging of bacteria grown in 10% PGRE revealed few or no flagella; however, no flagellin bands were observed during Western blot analysis. This apparent disparity might be explained by the fact that growth in PMs allows for a quantity of flagellin protein to be synthesized that is too small to be identified via Western blot but the observation of some flagella with SEM is still possible. On the other hand, PGP significantly depressed the swimming but not the swarming motility. This result suggests that this material has a different mechanism of action on bacterial motility and requires further investigation. There have been several studies aimed at identifying the therapeutic constituents of pomegranate (Braga et al., 2005; Jurenka, 2008).