Are Countries' Drink-Driving Policies Associated With Harms Involving Another Driver's Impairment?

INTRODUCTION: International drink-driving policy research generally focuses on aggregate outcomes (e.g., rates of crashes, fatalities) without emphasizing secondhand alcohol-related vehicular harms. In contrast, we investigate associations between drink-driving policies and harms involving another driver's impairment. METHODS: Alcohol's harms to others (AHTO) survey data from 12 countries (analytic N = 29,616) were linked to national alcohol policy data from the World Health Organization. We examined separately associations of two 12-month driving-related AHTOs (passenger with an impaired driver; vehicular crash involving someone else's drink driving) with 3 national drinking-driving policies-legal blood alcohol concentration (BAC) limits, use of random breath testing, use of sobriety checkpoints, and comprehensive penalties for drink-driving (community service, detention, fines, ignition interlocks, license suspension/revocation, mandatory alcohol treatment, vehicle impoundment, and penalty point system), plus 2 alcohol tax variables (having excise taxes and value-added tax [VAT] rate). Multilevel logistic regression addressed clustering of individuals within countries and subnational regions, while adjusting for individuals' gender, age, marital status, risky drinking, and regional drinking culture (% male risky drinkers in sub-national region). RESULTS: Controlling for national-, regional-, and individual-level covariates, comprehensive penalties were significantly and negatively associated with both outcomes; other vehicular policy variables were not significantly associated with either outcome. A society's VAT rate was negatively associated with riding with a drunk driver. Regional male drinking culture was positively associated with riding with an impaired driver, but was not significantly associated with being in a vehicular crash due to someone else's drinking. In both models, being male, being younger, and engaging in risky drinking oneself each were positively associated with vehicular harms due to someone else's drinking. CONCLUSIONS: Although results are associational and not causal, comprehensive penalties may be promising policies for mitigating driving-related harms due to another drinker. Higher VAT rate might reduce riding with a drunk driver.

Young men's behavioral competencies and risk of alcohol use disorder in emerging adulthood: Early protective effects of parental education.

We investigate how early exposure to parental externalizing behaviors (EB) may contribute to development of alcohol use disorders (AUD) in young adulthood, testing a developmental cascade model focused on competencies in three domains (academic, conduct, and work) in adolescence and emerging adulthood, and examining whether high parental education can buffer negative effects of parental EB and other early risk factors. We use data from 451,054 Swedish-born men included in the national conscript register. Structural equation models showed parental EB was associated with academic and behavioral problems during adolescence, as well as with lower resilience, more criminal behavior, and reduced social integration during emerging adulthood. These pathways led to elevated rates of AUD in emerging and young adulthood. Multiple groups analysis showed most of the indirect pathways from parental EB to AUD were present but buffered by higher parental education, suggesting early life experiences and competencies matter more for young men from lower socioeconomic status (SES) families than from higher SES families. Developmental competencies in school, conduct, and work are important precursors to the development of AUD by young adulthood that are predicted by parental EB. Occupational success may be an overlooked source of resilience for young men from low-SES families.

The Relationship Between the U.S. State Alcohol Policy Environment and Individuals' Experience of Secondhand Effects: Alcohol Harms Due to Others' Drinking.

BACKGROUND: Although restrictive state alcohol policy environments are protective for individuals' binge drinking, research is sparse on the effect of alcohol policies on alcohol's harms to others (AHTO). We examined the lagged associations between efficacy of U.S. state alcohol policies and number of harms from others' drinking 1 year later. METHODS: Individuals with AHTO data in a nationally representative sample of U.S. adults (analytic sample n = 26,744) that pooled the 2000, 2005, 2010, and 2015 National Alcohol Surveys and a 2015 National Alcohol's Harm to Others Survey were linked with prior-year state policy measures. We used 2 measures from the Alcohol Policy Scale (APS)-effectiveness in reducing (i) binge drinking and (ii) impaired driving, based on experts' efficacy judgments regarding 29 state alcohol policies. Three 12-month AHTO measures (due to another drinker) were experiencing: (i) either family/marriage difficulties or financial troubles; (ii) being assaulted or vandalized; and (iii) passenger with drunk driver or traffic accident. Multilevel models accounting for clustering within states and stratified by age-groups (<40 vs. ≥40) examined associations between the APS and AHTO measures, controlling for individual covariates (gender, race, education, employment and marital status, family problem-drinking history) of the victim. RESULTS: Only for those aged <40, the lagged APS-Binge drinking and APS-Impaired driving scores were each inversely associated with aggression-related harms and, separately, with drunk driving-related harm from someone else's drinking (ps < 0.05 to < 0.01). Family/financial harms were not associated with APS scores for either age-group. Composite AHTO measures (any of 3 harm-types) also were inversely associated with stronger state alcohol policy environments (ps < 0.05 to <0.01). CONCLUSIONS: State alcohol policies may be effective in reducing, to a meaningful degree, aggression-related harms and vehicular hazards due to other drinkers, but mainly in those under 40.

Age-dependent prognostic value of body mass index for non-metastatic clear cell renal cell carcinoma: A large multicenter retrospective analysis.

BACKGROUND AND OBJECTIVES: The prognostic value of obesity is unestablished for renal cell carcinoma. We assessed the age-dependent prognostic value of body mass index (BMI) in a large multicenter cohort of patients with non-metastatic clear cell renal cell carcinoma (nm-cRCC). METHODS: This study evaluated 2092 patients with nm-cRCC who underwent surgery with curative intent at five Korean institutions between 2001 and 2014. RESULTS: There was no significant difference in BMI between the young (<45 years) and older patients (≥45 years) (P = 0.398). Among older patients, high BMI (≥25 kg/m2 ) was associated with better 5-year rates of recurrence-free survival (RFS) and cancer-specific survival (CSS) (P = 0.003 and 0.004, respectively), and multivariate analysis confirmed that high BMI was independently associated with better RFS and CSS (RFS hazard ratio [HR]: 0.617, P = 0.005; CSS HR: 0.588, P = 0.024). However, among young patients, there were no significant BMI-related differences in the 5-year RFS and CSS rates (P = 0.457 and 0.420, respectively), and high BMI was not independently associated with RFS or CSS (P = 0.822 and 0.749, respectively). CONCLUSIONS: Among patients with nm-cRCC, high BMI was associated with a favorable prognosis among older patients but not among young patients. Therefore, the relationship between obesity and nm-cRCC prognosis might vary according to age.

Comparison of stratum corneum thickness between two proposed methods of calculation using Raman spectroscopic depth profiling of skin water content.

BACKGROUND/PURPOSE: The stratum corneum (SC) is the most important layer for the barrier function of skin, so investigation of the SC is very important in cosmetic and medical research. Here, we calculated the SC thickness using the depth profile of the skin's water concentration based on previously described methods, and then compared the results. METHODS: Seven Korean women in their 30s participated in this study. Raman spectroscopy was used to measure the in vivo depth profile of skin water concentration. A total of 21 areas were measured at forearm. Microsoft Excel 2007 was used to calculate SC thickness based on the slope and intersection methods. RESULTS: The slope method and the intersection method gave a forearm SC thickness calculated at 21.3 ± 2.6 µm and 17.6 ± 2.8 µm, respectively. There was a significant difference between the two calculation methods but the two methods showed strong correlation of SC thickness results (r = .899). CONCLUSION: Although there was a difference in calculated SC thickness of about 20% between the two methods, these results reveal that the two SC thickness calculation methods using Raman spectroscopy were suitable for measuring SC thickness, a finding consistent with other published results.

Impact of preoperative calculation of nephron volume loss on future of partial nephrectomy techniques; planning a strategic roadmap for improving functional preservation and securing oncological safety.

OBJECTIVES: To assess the correlation of the resected and ischaemic volume (RAIV), which is a preoperatively calculated volume of nephron loss, with the amount of postoperative renal function (PRF) decline after minimally invasive partial nephrectomy (PN) in a multi-institutional dataset. PATIENTS AND METHODS: We identified 348 patients from March 2005 to December 2013 at six institutions. Data on all cases of laparoscopic (n = 85) and robot-assisted PN (n = 263) performed were retrospectively gathered. Univariable and multivariable linear regression analyses were used to identify the associations between various time points of PRF and the RAIV, as a continuous variable. RESULTS: The mean (sd) RAIV was 24.2 (29.2) cm3 . The mean preoperative estimated glomerular filtration rate (eGFR) and the eGFRs at postoperative day 1, 6 and 36 months after PN were 91.0 and 76.8, 80.2 and 87.7 mL/min/1.73 m2 , respectively. In multivariable linear regression analysis, the amount of decline in PRF at follow-up was significantly correlated with the RAIV (ß 0.261, 0.165, 0.260 at postoperative day 1, 6 and 36 months after PN, respectively). This study has the limitation of its retrospective nature. CONCLUSION: Preoperatively calculated RAIV significantly correlates with the amount of decline in PRF during long-term follow-up. The RAIV could lead our research to the level of prediction of the amount of PRF decline after PN and thus would be appropriate for assessing the technical advantages of emerging techniques.

Enhanced sensitivity and responses to viologens from a whole-cell bacterial bioreporter treated with branched polyethyleneimines.

AIMS: Evaluate the use of polyethyleneimines (PEIs) as membrane permeabilizers to improve the responses and sensitivity of a bacterial bioreporter strain to viologens. METHODS AND RESULTS: The responses from E. coli str. EBS, i.e., E. coli BW25113 carrying plasmid pSDS, when exposed to five different viologens were characterized, as were the toxicities of seven different PEIS, including two linear and five branched species. Based on these results, benzyl viologen led to the greatest responses, and 0·8-kDa branched PEI (BPEI) was the least toxic of the PEIs tested and, therefore, both were selected for the subsequent tests. The bioluminescence and relative responses from E. coli str. EBS exposed to various concentrations of 0·8 kDa BPEI identified 400 mg l-1 as the optimal concentration. Using this concentration, tests were performed with all five of the viologens. CONCLUSIONS: The responses from E. coli str. EBS to the viologens were improved, with the maximum relative bioluminescence values increasing between 5·6 and 16·5-fold. The minimum detectable levels for four of the viologens were likewise improved 2- to 4-fold. SIGNIFICANCE AND IMPACT OF STUDY: Improving bacterial membrane permeability in a controlled manner using BPEIs can improve biosensing of toxic compounds, as well as be used in biofuel and bioenergy applications where membrane permeability to a solute is important.

Gastrointestinal stromal tumours (GISTs) with a thousand faces: atypical manifestations and causes of misdiagnosis on imaging.

Gastrointestinal stromal tumours (GISTs) can lead to emergency situations, such as gastrointestinal bleeding, intestinal obstruction, and tumoural rupture with haemoperitoneum or peritonitis. In addition, if a GIST grows exophytically to a large size, it is often misdiagnosed as a tumour arising from adjacent organs. Sometimes, the atypical appearance of GISTs on imaging causes diagnostic confusion. In this article, we illustrate a variety of GISTs with atypical presentations and also discuss the important diagnostic clues for differentiating GISTs from other lesions.

Gallbladder carcinoma: causes of misdiagnosis at CT.

Gallbladder carcinomas can present with varied imaging features on computed tomography. The three major imaging features include (1) focal or diffuse wall thickening with or without irregularity of the gallbladder; (2) polypoidal intraluminal mass; and (3) large mass obscuring and replacing the gallbladder, often extending to the liver. Patterns of wall thickening or polypoid growth are often confused with various benign gallbladder diseases due to overlap of imaging findings. Moreover, gallbladder carcinomas that coexist with benign gallbladder diseases make accurate preoperative diagnosis more difficult. Recently, high-resolution ultrasound (HRUS) has been regarded as a problem-solving tool for gallbladder diseases. In this article, we will illustrate various imaging presentations of gallbladder cancer, along with imaging pitfalls and recently updated HRUS findings.

Radotinib-induced lentiginosis: a report of an adverse cutaneous reaction associated with a tyrosine kinase inhibitor.

Tyrosine kinase inhibitors (TKIs) are associated with various adverse cutaneous reactions, including pigmentary changes. Radotinib is a novel and selective BCR-ABL1 TKI, which has shown activity and safety in the treatment of patients with chronic myeloid leukaemia resistant or intolerant to imatinib. A 69-year-old Korean man presented with lentiginosis after taking radotinib for 6 months. On histopathological examination, the numbers of melanocytes and melanin pigment were found to be increased due to c-KIT activation, consequently upregulating microphthalmia-associated transcription factor. This finding is in contrast to previous reports analysing the mechanisms of previously reported tyrosine kinase inhibitors inhibiting c-KIT.

Secondary cutaneous lymphoma: comparative clinical features and survival outcome analysis of 106 cases according to lymphoma cell lineage.

BACKGROUND: The relative frequency, clinical features and survival outcomes of secondary cutaneous lymphoma remain poorly understood. OBJECTIVES: To determine the clinical characteristics and survival outcomes of secondary cutaneous lymphoma. MATERIALS AND METHODS: The present retrospective cohort study included all 106 patients who presented with secondary cutaneous lymphoma. Patient medical records were reviewed to determine the clinical features, survival outcomes and prognostic factors. Survival outcomes were analysed by using the Kaplan-Meier method and comparisons between lymphoma cell lineages [T or natural killer (T-/NK)-cell vs. B-cell lymphoma] were performed using the log-rank test. RESULTS: Secondary cutaneous lymphomas consisted of mature T-/NK-cell lymphomas (56%), mature B-cell lymphomas (35%), immature haematopoietic malignancies (8%) and Hodgkin lymphoma (1%). The T-/NK-cell lineage lymphoma cases were more likely to have multiple and disseminated skin lesions than the B-cell lineage lymphoma cases. The lymphoma cell lineage did not significantly influence survival outcomes. Patients who showed cutaneous involvement within 6 months of the initial diagnosis of primary disease had a poorer overall survival (OS) outcome than patients who developed cutaneous dissemination 6 or more months after the initial diagnosis (P < 0.001). Patients with disseminated skin lesions had a poorer OS than patients with localized skin lesions (P = 0.028). The two lymphoma cell lineages differed in terms of prognostic factors that influenced survival. CONCLUSIONS: Skin lesion characteristics such as time point of appearance and extent affect the survival outcomes of secondary cutaneous lymphoma. Cell lineage did not influence survival outcomes but the two lineages are associated with different prognostic factors.

Ambulatory-treated Clostridium difficile infection: a comparison of community-acquired vs. nosocomial infection.

The purpose of this study was to identify the clinical outcomes of ambulatory-treated Clostridium difficile infection (CDI) and risk factors associated with community-associated CDI (CA-CDI). Adult patients diagnosed with CDI in the institutional or ambulatory-care setting between 1 April 2005 and 30 April 2011, with no other CDI diagnosis in the previous 180 days, and who purchased an ambulatory, anti-CDI agent within 7 days of CDI diagnosis were included. A total of 1201 patients were included with 914 (76%) and 287 (24%) identified with CA-CDI and nosocomial CDI (N-CDI), respectively. Patients with N-CDI were more likely to have had a recurrent CDI (P = 0·043) and died from any cause (P < 0·001). Patients with CA-CDI were younger, healthier, and had fewer traditional risk factors compared to patients with N-CDI. To prevent CA-CDI, clinicians should be aware that patients at risk for CA-CDI are unique from those at risk for N-CDI.

Facial and extrafacial eosinophilic pustular folliculitis: a clinical and histopathological comparative study.

BACKGROUND: Although more than 300 cases of eosinophilic pustular folliculitis (EPF) have been reported to date, differences in clinicohistopathological findings among affected sites have not yet been evaluated. OBJECTIVES: To evaluate differences in the clinical and histopathological features of facial and extrafacial EPF. METHODS: Forty-six patients diagnosed with EPF were classified into those with facial and extrafacial disease according to the affected site. Clinical and histopathological characteristics were retrospectively compared, using all data available in the patient medical records. RESULTS: There were no significant between-group differences in subject ages at presentation, but a male predominance was observed in the extrafacial group. In addition, immunosuppression-associated type EPF was more common in the extrafacial group. Eruptions of plaques with an annular appearance were more common in the facial group. Histologically, perifollicular infiltration of eosinophils occurred more frequently in the facial group, whereas perivascular patterns occurred more frequently in the extrafacial group. Follicular mucinosis and exocytosis of inflammatory cells in the hair follicles were strongly associated with facial EPF. CONCLUSIONS: The clinical and histopathological characteristics of patients with facial and extrafacial EPF differ, suggesting the involvement of different pathogenic processes in the development of EPF at different sites.

Ethnic drinking cultures, gender, and socioeconomic status in Asian American and Latino drinking.

BACKGROUND: Heterogeneity in drinking across national groups is well documented, but what explains such heterogeneity is less clear. To improve understanding of the underlying cultural conditions that may lead to diverse drinking outcomes, we investigate whether 3 dimensions of ethnic drinking culture (EDC)-alcohol consumption level, drinking prevalence, and detrimental drinking pattern (DDP) in the country of origin (COO)-are significantly associated with alcohol consumption in Asian Americans and Latina/os, and whether the associations vary by gender and socioeconomic status (SES) as assessed by educational level. METHODS: A nationally representative sample of 1,012 Asian American and 4,831 Latino adults extracted from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions data was used. A series of multiple logistic and linear regression models were fitted separately for Asian Americans and for Latinos. Analyses were also stratified by gender and educational level. RESULTS: Overall, the associations between EDC variables and drinking outcomes were more pronounced for all Asian Americans than for all Latina/os, for males than for females among Asian Americans, and for Latinas than for Latinos. In analyses simultaneously stratifying on gender and education level, however, there was a clear pattern of COO DDP associated with heavier drinking and alcohol consumption volume only for Latinos without a college degree. CONCLUSIONS: Ethnic drinking cultures may influence drinking in Asian American and Latino subgroups, albeit to a varying degree. Low-SES Latinos may be at disproportionate risk of harmful drinking patterns pervasive in their COO. Future research might investigate the complex interplay between socioeconomic disadvantage and cultural conditions to inform targeted interventions for subgroups at high risk of alcohol-related harms.

Right ventricular adaptation to pulmonary pressure load in patients with chronic thromboembolic pulmonary hypertension before and after successful pulmonary endarterectomy--a cardiovascular magnetic resonance study.

BACKGROUND: The aim of the study was to characterize RV adaptation to varying loading conditions in patients with chronic thromboembolic hypertension (CTEPH) before and after pulmonary endarterectomy (PEA). Nearly 4% of patients with pulmonary embolism develop CTEPH. PEA offers a cure with excellent outcome. By use of cardiovascular magnetic resonance (CMR) combined with hemodynamic measurements pulmonary arterial elastance (Ea-pulm_i), end-systolic right ventricular elastance (Ees-RV_i) and ventriculo-arterial coupling (Ea-pulm_i/Ees-RV_i) can be studied before and after PEA. METHODS: Sixty-five patients (mean age 41±12 years, 28 female) underwent CMR pre- and post-PEA. Ejection fraction (EF), end-diastolic (EDVi), end-systolic (ESVi), and stroke (SVi) volumes were indexed for body surface area. Ea-pulm_i was calculated as pulmonary artery mean pressure (mPAP)/SVi, and Ees-RV_i as mPAP/ESVi. RESULTS: mPAP decreased from 47±12 to 25±9 mmHg, p=0.0001. Ea-pulm_i was increased before PEA and normalized afterwards (2.8±2.1 vs. 0.85±0.4 mmHg/ml/m2, p=0.0001). Ees-RV_i was depressed before and after PEA (0.72±0.27 vs. 0.66±0.3 mmHg/ml/m2, p=0.13). EF improved from 25±12% to 46±10%, p=0.0001, because ventriculo-arterial coupling was restored (4.2±3 vs. 1.4±0.6, p=0.0001). EDVi and ESVi mproved significantly (EDVi 92±32 to 72±23 ml, p=0.0001; ESVi 69±31 to 41±18 ml, p=0.0001). CONCLUSION: RV function is largely determined by afterload and returns to normal once afterload is normalized. This is paralleled by a significant improvement of CMR indices of right ventricular remodelling.

When the Going Gets Tough: Multimorbidity and Heavy and Binge Drinking Among Adults.

INTRODUCTION: Multimorbidity, the presence of two or more long-term health conditions in the same individual, is an emerging epidemic associated with increased morbidity and mortality. Continued drinking concurrent with alcohol-related chronic conditions, particularly with multimorbidity, is likely to further elevate health risk. This study aimed to examine the associations of multimorbidity among diabetes, hypertension, heart disease, and cancer with drinking, and moderation of these associations by age. METHODS: Logistic regression modeling was performed in 2023 using a nationally representative sample of U.S. adults from the 2015-19 National Survey on Drug Use and Health. Multimorbidity was assessed using (1) a count of these conditions and (2) disease-specific categories. The outcomes were past month heavy drinking (7+/14+ drinks weekly) and binge drinking (4+/5+ drinks per occasion) for women and men. RESULTS: A pattern of reduced odds for drinking outcomes associated with a greater degree of multimorbidity was found. This pattern was more apparent in models using the continuous measure of multimorbidity than in those using the categorical measure, and more consistent for binge drinking than for heavy drinking and for women than for men. Significant age interactions were found: the log odds of heavy drinking and binge drinking for both men and women decreased as the number of conditions increased, and more steeply for those ages 50+ than the younger. The log odds of heavy drinking varied little among men under age 50 regardless of multimorbidity. CONCLUSIONS: Alcohol interventions to reduce drinking with multimorbidity, particularly among heavy-drinking men under age 50, are warranted.

Gastric intestinal metaplasia regression in United States population: A retrospective longitudinal study.

Background and Aim: Gastric cancer is a health concern and contributes to cancer-related deaths. Gastric intestinal metaplasia (GIM) is a premalignant lesion of gastric cancer. Currently, factors associated with GIM regression are under-investigated. This study aims to assess the rate of GIM regression and identify factors associated with it. Methods: This study was conducted at Medstar Washington Hospital Center. We included patients who had GIM between January 2015 and December 2020. Population was divided into GIM persistence or regression. Data included demographics, esophagogastroduodenoscopy findings, Helicobacter pylori status, and laboratory results. Statistical analyses included Kaplan-Meier and Cox proportional models to explore predictors of GIM regression. Results: Among 2375 patients, 9.1% had GIM. Notably, 85 patients had GIM regression and 132 patients had persistent GIM. African Americans constituted (75%) of the regression group and (76%) of the persistence group. Peptic ulcer disease (PUD) was noted in 12.9% of the regression group at baseline, and 5.9% at follow-up; the persistence group showed 11.4% at baseline and 5.3% at follow-up (P = 0.89). Regression analysis revealed that the presence of PUD was associated with a higher rate of regression (hazard ratio [HR] 2.46, P = 0.013). Smoking status showed lower rates of regression (HR 0.54 and 0.62, P = 0.038 and 0.169). On gastric mapping, African Americans, Hispanics, and individuals of other races/ethnicities displayed lower rates of GIM regression (HR 0.68, 0.78 and 0.69). Conclusion: PUD was associated with a higher rate of GIM regression, while smoking showed lower regression rates. Results provide insights into factors influencing GIM regression in African American population and may inform future surveillance and treatment strategies.

MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas.

The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P<0.0001), increased copy number gain (r=0.393, P=0.000002) and amplification of MET gene. Moreover, patients with MET overexpression showed shorter overall survival (HR, 1.781; 95% CI, 1.324-2.395; P<0.001) and disease-free survival (HR, 1.765; 95% CI, 1.227-2.541; P=0.002) compared with patients without MET overexpression. However, membranous overexpression of MET did not highly correlate with mRNA level (r=0.274, P=0.002), copy number gain or survival (P>0.05). We developed highly correlating interpretation methods of MET immunohistochemistry in gastric carcinomas. MET overexpression is an independent prognostic factor and could be a potential target and predictor of benefit for targeted therapy with MET inhibitors.

Evolving fisher kernels for biological sequence classification.

Fisher kernels have been successfully applied to many problems in bioinformatics. However, their success depends on the quality of the generative model upon which they are built. For Fisher kernel techniques to be used on novel problems, a mechanism for creating accurate generative models is required. A novel framework is presented for automatically creating domain-specific generative models that can be used to produce Fisher kernels for support vector machines (SVMs) and other kernel methods. The framework enables the capture of prior knowledge and addresses the issue of domain-specific kernels, both of which are current areas that are lacking in many kernel-based methods. To obtain the generative model, genetic algorithms are used to evolve the structure of hidden Markov models (HMMs). A Fisher kernel is subsequently created from the HMM, and used in conjunction with an SVM, to improve the discriminative power. This paper investigates the effectiveness of the proposed method, named GA-SVM. We show that its performance is comparable if not better than other state of the art methods in classifying secretory protein sequences of malaria. More interestingly, it showed better results than the sequence-similarity-based approach, without the need for additional homologous sequence information in protein enzyme family classification. The experiments clearly demonstrate that the GA-SVM is a novel way to find features with good performance from biological sequences, that does not require extensive tuning of a complex model.