Class II:2 malocclusion-prevalence and progression of labial gingival recessions during Herbst-Multibracket appliance treatment.

OBJECTIVES: To determine the prevalence, incidence, and changes in magnitude of labial gingival recessions (LGR) in class II:2 patients during Herbst-Multibracket appliance (Herbst-MBA) treatment (Tx) plus retention. SUBJECTS AND METHODS: All class II:2 patients of the Department of Orthodontics, University of Giessen, Germany who completed Herbst-MBA Tx (mean pre-Tx age 15.6 years). The cohort had undergone a Herbst phase (mean 8.1 months) as well as a subsequent MBA phase (mean 14.4 months). Study casts were evaluated from pre-Tx and after Herbst-MBA Tx plus ≥ 24 months of retention. RESULTS: Ratable pre-Tx and post-retention study casts (total observation period 53.5 ± 10.3 months) were available from 94 out of 173 patients. No significant difference existed regarding pre-Tx LGR data between patients with and without complete records. The prevalence for teeth with LGR ≥ 0.5 mm was 1.4% pre-Tx respectively 6.7% post-retention. The highest values of up to 5.3% (pre-Tx) and 20.2% (post-retention) were determined for the upper first premolars and lower central incisors. Incidence values of 4.7% (all teeth) and up to 14.9% (upper first right premolars) respectively 11.1% (lower central incisors) were calculated (LGR ≥ 0.5 mm). The overall LGR mean magnitudes were 0.01 mm pre-Tx respectively 0.06 mm post-retention. CONCLUSIONS: For the prevalence of LGR ≥ 0.5 mm an average increase of 5.3% was determined during ≈ 4.5 years of Herbst-MBA Tx plus retention. The highest incidence was seen for lower central incisors and upper right premolars (11.1/14.9%). The overall LGR mean magnitude increased by 0.05 mm. CLINICAL RELEVANCE: Herbst-MBA Tx is a common approach for class II:2 malocclusions. Very little, however, is known regarding LGR development in respective patients.

Prevalence of WNT10A gene mutations in non-syndromic oligodontia.

OBJECTIVES: Non-syndromic oligodontia is an infrequent clinical condition whose etiology is not yet completely understood being a wide spectrum of gene mutations described in concomitance with this severe form of tooth agenesis. Recently, multiple observations have linked up to 50% of cases with isolated hypodontia to mutations in the WNT10A gene. Here, we hypothesized that mutations in the WNT10A gene could also be present in families affected by non-syndromic oligodontia. MATERIAL AND METHODS: All available patients with non-syndromic oligodontia (n = 20) treated at the Department of Orthodontics, University of Giessen, Germany between 1986 and 2013 as well as their family members were analyzed for mutations in the WNT10A gene. RESULTS: Mutation screening was positive in 50% of the 20 patients. The analysis revealed that the mutations 2:219755011(c.682T>TA)(p.F228I), 2:219754822(c.493G>GA)(p.G165R), 2:219754816(c.487C>CT)(p.R163W), and 2:219747090(c.321C>CA)(p.C107*), the novel missense mutation 2:219757676(c.937G/GT)(p.G313C), and the novel synonym variant 2:219754854(c.525C>CT)(p.H175H) were present. CONCLUSION: Multiple phenotypes are found in individuals presenting mutations in the WNT10A gene. Among them, the stop codon p.C107* as well as the biallelic p.F228I variants correlate with the most severe oligodontia phenotypes. In addition, we diagnosed the monoallelic mutations p.F228I, p.G165R, and p.G313C in healthy relatives with normal dentitions. CLINICAL RELEVANCE: A correct diagnosis of non-syndromic oligodontia is fundamental to discard a possible underlying pathology in which multiple tooth agenesis could be the most evidential clinical sign. Due to the wide spectrum of pathologies that are associated to mutations in the WNT10A gene, an extended genetic analysis of these individuals' relatives is also essential.

[S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium : Requirements for pathology]. / S3-Leitlinie Diagnostik und Therapie des Endometriumkarzinoms : Anforderungen an die Pathologie.

The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.

Association of intracortical myelin and cognitive function in bipolar I disorder.

OBJECTIVE: Although cognitive dysfunction persists through affective and euthymic states in bipolar disorder (BD), its neurobiological correlates remain undetermined. We explore whole-cortex intracortical myelin (ICM) and cognition in BD-I and controls. METHODS: T1 -weighted images (3T) optimized for ICM measurement were analyzed using a surface-based approach. MRI signal was sampled at cortical mid-depth. Cognitive performance was measured via standardized computerized battery and paper-and-pencil Trails B. RESULTS: ICM was associated with verbal memory (VM) in BD throughout a cortical network identified with pertinence to VM function, with strongest effects in left caudal middle temporal cortex and left dorsolateral prefrontal cortex (Pcorrected  < 0.05). Subanalyses revealed specific association with correct word recognition, without delay. Processing speed, executive function, and reaction time were also predicted by ICM in BD, but not controls, although this did not survive Bonferroni correction. CONCLUSION: This is the first study to show VM association with ICM in BD. ICM has been implicated in the integrity of neural connections and neural synchrony. VM dysfunction is one of the most replicated cognitive abnormalities in BD. Therefore, these results provide a novel mechanism for understanding cognitive dysfunction in BD, which can aid in the development of targeted therapeutics to improve cognitive outcomes in BD.

Predictive value of dysregulation profile trajectories in childhood for symptoms of ADHD, anxiety and depression in late adolescence.

We examined whether there are certain dysregulation profile trajectories in childhood that may predict an elevated risk for mental disorders in later adolescence. Participants (N = 554) were drawn from a representative community sample of German children, 7-11 years old, who were followed over four measurement points (baseline, 1, 2 and 6 years later). Dysregulation profile, derived from the parent report of the Strengths and Difficulties Questionnaire, was measured at the first three measurement points, while symptoms of attention deficit hyperactivity disorder (ADHD), anxiety and depression were assessed at the fourth measurement point. We used latent class growth analysis to investigate developmental trajectories in the development of the dysregulation profile. The predictive value of dysregulation profile trajectories for later ADHD, anxiety and depression was examined by linear regression. For descriptive comparison, the predictive value of a single measurement (baseline) was calculated. Dysregulation profile was a stable trait during childhood. Boys and girls had similar levels of dysregulation profile over time. Two developmental subgroups were identified, namely the low dysregulation profile and the high dysregulation profile trajectory. The group membership in the high dysregulation profile trajectory (n = 102) was best predictive of later ADHD, regardless of an individual's gender and age. It explained 11% of the behavioural variance. For anxiety this was 8.7% and for depression 5.6%, including some gender effects. The single-point measurement was less predictive. An enduring high dysregulation profile in childhood showed some predictive value for psychological functioning 4 years later. Hence, it might be helpful in the preventive monitoring of children at risk.

Orthodontic Class II:1 treatment-efficiency and outcome quality of Herbst-multibracket appliance therapy.

OBJECTIVES: The aim of this retrospective investigation was to assess the efficiency and outcome quality of Class II:1 treatment (Tx). MATERIAL AND METHODS: The investigation is based on the evaluation of all Class II:1 patients that ever (1986-2014) started Tx with a Herbst appliance and subsequently a multibracket appliance (MBA) at the study center. Study casts from before Tx, after Herbst-MBA Tx, and (if available) after ≥ 24 months of retention were evaluated using the Peer Assessment Rating (PAR) index, the Ahlgren scale, and standard occlusal variables. RESULTS: In total, 526 Class II:1 patients with a mean pre-Tx age of 14.4 years (range 9.8-44.4) had received Herbst-MBA Tx; 18 patients discontinued Tx before completion. For 240 patients, data from ≥ 24 months of retention were available. The pre-Tx PAR score of 32.4 ± 8.83 was reduced to 8.0 ± 4.51 during Tx. A slight increase to 8.8 ± 5.11 occurred during retention. The percentage of patients which could be assigned to the category "greatly improved" was 62% after Tx and 57% after retention; only 2-3% had to be assigned to the category "worse/no different." The outcome ratings according to the Ahlgren scale revealed 17% excellent, 35% good, 45% satisfactory, and 3% unsuccessful results. CONCLUSIONS: Class II:1 Tx using Herbst-MBA is an efficient approach in orthodontic care. During a mean active Tx period of 2 years, high-quality results can be obtained in the majority of patients. CLINICAL RELEVANCE: The present investigation is the first to investigate a large unselected cohort of consecutive Herbst-MBA patients to determine representative data on the efficiency and the outcome quality of this Tx approach.

The feasibility of K XRF bone lead measurements in mice assessed using 3D-printed phantoms.

This article describes the development of a system forin vivomeasurements of lead body burden in mice using109Cd K x-ray fluorescence (XRF). This K XRF system could facilitate early-stage studies on interventions that ameliorate or reverse organ tissue damage from lead poisoning by reducing animal numbers through a cross-sectional study approach. A novel mouse phantom was developed based on a mouse atlas and 3D-printed using PLA plastic with plaster of Paris 'bone' inserts. PLA plastic was found to be a good surrogate for soft tissue in XRF measurements and the phantoms were found to be good models of mice. As expected, lead detection limits varied with mouse size, mouse orientation, and mouse position with respect to the source and detector. The work suggests that detection limits of 10 to 20µg Pb per g bone mineral may be possible for a 2 to 3 hour XRF measurement in a single animal, an adequate limit for some pre-clinical studies. The109Cd K XRF mouse measurement system was also modeled using the Monte Carlo code MCNP. The combination of experiment and modeling found that contrary to expectation, accurate measurements of lead levels in mice required calibration using mouse-specific calibration standards due to the coherent scatter peak normalization failing when small animals are measured. MCNP modeling determined that this was because the coherent scatter signal from soft tissue, which until now has been assumed negligible, becomes significant when compared to the coherent scatter signal in bone in small animals. This may have implications for some human measurements. This work suggests that109Cd K x-ray fluorescence measurements of lead body burden are precise enough to make the system feasible for small animals if appropriately calibrated. Further work to validate the technology's measurement accuracy and performancein vivowill be required.

Quantitative assessment of cell viability based on flow cytometry and microscopy.

We compare flow cytometric and microscopic determination of cell viability by fluorescence labeling using calcein acetoxy-methyl-ester and ethidium homodimer-1 as live and dead stain, respectively. Peripheral blood monocytes served as model system and were accumulated applying density gradients. Subsequently, monocytes were further enriched by magnetic-activated or fluorescence-activated cell sorting (MACS, FACS) targeting the antigen CD14. Identical samples were used for flow cytometric and microscopic analysis to allow direct comparison of both analysis methods. More than 1,000 cells were measured for each sample to minimize the measurement uncertainty caused by counting statistics. We observed good agreement of flow cytometric and microscopic viability measurements. On average, the difference in viability measured by flow cytometry and microscopy amounted to (2.7 ± 1.4)% for live staining and (1.7 ± 1.2)% for dead staining. These deviations were similar to the uncertainty of measurement for cell viability, thus demonstrating that both methods delivered equal results. Besides monocytes, comparison of flow cytometric and microscopy viability for MACS enriched CD34-positive cells also showed consistent results.

Quality of orthodontic care-A multicenter cohort study in Germany : Part 1: Evaluation of effectiveness of orthodontic treatments and predictive factors.

AIMS: Orthodontic care and its effectiveness have increasingly become the focus of political and public attention in the recent past. Therefore, this multicenter cohort study aimed to report about the effectiveness of orthodontic treatments in Germany and to identify potential influencing factors. METHODS: A total of 586 patients from seven German study centers were screened for this cohort study, of which 361 patients were recruited at the end of their orthodontic treatment. Of these, 26 patients had missing study models and/or missing treatment information. Thus, 335 participants were included. The severity of malocclusion was rated using the Peer Assessment Rating (PAR) Index at baseline (T0) retrospectively and-prospectively-after the retention period (T1). Practitioner-, treatment- and patient-related information were analyzed in order to detect potential predictive factors for treatment effectiveness. RESULTS: Study participants (202 female and 133 male) were on average 14.8 (standard deviation [SD] ± 6.1) years old at start of active treatment. Average PAR score at T0 was 25.96 (SD ± 10.75) and mean posttreatment PAR score was 3.67 (SD ± 2.98) at T1. An average decrease of total PAR score by 22.30 points (SD ± 10.73) or 83.54% (SD ± 14.58; p < 0.001) was detected. Furthermore, 164 treatments (49.1%) were categorized as 'greatly improved' but only 3 treatments (0.9%) as 'worse or no different'; 81.5% of all cases finished with a high-quality treatment outcome (≤5 PAR points at T1). Logistic regression analyses detected staff experience as a significant predictive factor for high-quality results (odds ratio 1.27, p = 0.001, 95% confidence interval 1.11-1.46). CONCLUSION: The improvement rate among this selected German cohort indicated an overall very good standard of orthodontic treatment. Staff experience proved to be a predictive factor for high-quality results.

Herbst-multibracket appliance treatment: is there an association between lower incisor position changes and the development of labial gingival recessions?

PURPOSE: To assess a potential association between lower incisor (LI) position changes during Herbst-multibracket appliance (Herbst-MBA) treatment and the development of labial gingival recessions (LGR). METHODS: All class II patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who had undergone Herbst-MBA treatment until 2015 with study models and lateral cephalograms available from before (T0) and after treatment plus ≥24 months of retention (T3) were included (n = 259). Lateral cephalograms were evaluated regarding LI position changes: iiL/ML (angle between LI long axis and mandibular plane [MP]), ii-MLPg (distance between LI incisal edge and a line perpendicular to MP through pogonion), apex-MLPg (distance between LI apex and a line perpendicular to MP through pogonion), ii-MLii (distance between LI incisal edge and MP on a line perpendicular to MP through incisal edge). Using study models the distance between the cementoenamel junction and the deepest point of the gingival margin was defined as LGR. RESULTS: The following cephalometric mean changes were recorded (T0-T3): iiL/ML +5.9 ± 5.76° (p = 0.929), ii-MLPg -0.2 ± 0.25 mm (p = 0.430), apex-MLPg +0.1 ± 0.32 mm (p = 0.363), ii-MLii +0.1 ± 0.36 mm (p = 0.206). The mean increase of LGR magnitude measured on the study models was 0.1 ± 0.35 mm. However, no association with the cephalometric LI position changes was found (|R| ≤ 0.2). CONCLUSION: There is no association between the amount of LI position changes and the development of LGR during Herbst-MBA treatment plus retention. Nevertheless, individual predisposition or excessive treatment changes and extraordinary treatment approaches, respectively, might still lead to development of LGR.

Maternal and neonatal outcome after vaginal breech delivery at term after cesarean section - a prospective cohort study of the Frankfurt breech at term cohort (FRABAT).

OBJECTIVE: To compare the neonatal and maternal outcomes as well as the mode of delivery of intended vaginal breech deliveries in women with a prior cesarean section to primiparous patients. STUDY DESIGN: The prospective monocenter cohort study was conducted among 604 women who presented for an intended vaginal singleton breech delivery at term between January 2007 and December 2016. RESULTS: Out of 37 women with a prior cesarean 19 had a successful vaginal delivery. 344 of 567 primiparous women had a successful vaginal delivery. Neonatal morbidity and mortality as well as maternal outcome were not significantly different in successful vaginal deliveries of women with prior cesarean compared to primiparous patients. The cesarean section rate was not significantly higher in the group of women with a prior cesarean (49%) compared to the group of primipara (39%). CONCLUSION: A prior cesarean should not be taken as an exclusion criterion for a planned vaginal delivery out of a breech presentation at term. Large multicenter, case-controlled studies are necessary to implement international guidelines.

Provider-initiated HIV testing and counseling in TB clinical settings: tools for program implementation.

In countries with high HIV prevalence, up to 80% of tuberculosis (TB) patients also have human immunodeficiency virus (HIV) infection. HIV testing and counseling needs to be more feasible and accessible to all people in settings with a generalized HIV epidemic, but particularly to those likely to have HIV infection and who need care and treatment. Implementing provider-initiated and -delivered HIV testing and counseling (PITC) in clinical settings where patients have symptoms and signs consistent with HIV-related disease, including TB, is therefore a priority. We describe a new tool that has been developed to assist countries in planning and implementing PITC in TB clinical settings. The materials include a template for national guidance for the PITC program and procedures, a training curriculum for clinic staff and job aids including a script that assist clinicians in communicating appropriate pre- and post-test information to their TB patients, including the benefits to HIV-infected TB patients of knowing their status so they can obtain HIV care and treatment and prevent the spread of HIV.

Tuberculosis risk among staff of a large public hospital in Kenya.

SETTING: In sub-Saharan Africa, high rates of tuberculosis (TB) and human immunodeficiency virus (HIV) infection pose a serious threat for occupationally acquired TB among health care workers. OBJECTIVE: To identify factors associated with TB disease among staff of an 1800-bed hospital in Kenya. DESIGN: We calculated TB incidence among staff and conducted a case-control study where cases (n = 65) were staff diagnosed with TB and controls (n = 316) were randomly selected staff without recent TB. RESULTS: The annual incidence of TB from 2001 to 2005 ranged from 645 to 1115 per 100000 population. Factors associated with TB disease were additional daily hours spent in rooms with patients (adjusted odds ratio [aOR] 1.3, 95%CI 1.2-1.5), working in areas where TB patients received care (aOR 2.1, 95%CI 1.1-4.2), HIV infection (aOR 29.1, 95%CI 5.1-167) and living in a slum (aOR 4.7, 95%CI 1.8-12.5) or hospital-provided low-income housing (aOR 2.6, 95%CI 1.2-5.6). CONCLUSION: Hospital exposures were associated with TB disease among staff at this hospital regardless of their job designation, even after controlling for living conditions, suggesting transmission from patients. Health care facilities should improve infection control practices, provide quality occupational health services and encourage staff testing for HIV infection to address the TB burden in hospital staff.

Long-term effects of Class II orthodontic treatment on oral health.

AIM: To investigate the long-term (≥15 years) benefit of orthodontic Class II treatment (Tx) on oral health (OH). SUBJECTS AND METHODS: All patients (Department of Orthodontics, University of Giessen, Giessen, Germany) who underwent Class II correction (Herbst-multibracket Tx, end of active Tx ≥ 15 years ago) and agreed to participate in a recall (clinical examination, interview, impressions, and photographs) were included. Records after active Tx were used to assess the long-term OH effects. Data were compared to corresponding population-representative age-cohorts as well as to untreated Class I controls without orthodontic Tx need during adolescence. RESULTS: Of 152 treated Class II patients, 75 could be located and agreed to participate at 33.7 ± 3.0 years of age (pre-Tx age: 14.0 ± 2.7 years). The majority (70.8%) were fully satisfied with their teeth and with their masticatory system. The Decayed, Missing, Filled Teeth Index (DMFT) was 7.1 ± 4.8 and, thus, almost identical to that of the untreated Class I controls (7.9 ± 3.6). In contrast, the DMFT in the population-representative age-cohort was 56% higher. The determined mean Community Periodontal Index (CPI) maximum score (1.6 ± 0.6) was also comparable to the untreated Class I controls (1.7 ± 0.9) but in the corresponding population-representative age-cohort it was 19-44% higher. The extent of lower incisor gingival recessions did not differ significantly between the treated Class II participants and the untreated Class I controls (0.1 ± 0.2 vs. 0.0 ± 0.1 mm). CONCLUSION: Patients with orthodontically treated severe Class II malocclusions had a lower risk for oral health impairment than the general population. The risk corresponded to that of untreated Class I controls (without orthodontic Tx need during adolescence).

Tuberculosis case finding and preventive therapy in an HIV voluntary counseling and testing center in Uganda.

SETTING: A large, urban human immunodeficiency virus (HIV) voluntary counseling and testing (VCT) center in Kampala, Uganda. OBJECTIVE: Tuberculosis (TB) is a leading cause of morbidity and mortality in persons with HIV infection in sub-Saharan Africa. Intensified TB case finding and use of isoniazid preventive therapy (IPT) for latent infection reduces the burden of TB, but few programs have been implemented due to concerns about feasibility. DESIGN: Retrospective evaluation of a TB case finding and IPT program. RESULTS: Over a 25-month period, 6305 patients newly diagnosed with HIV infection underwent evaluation: 293 (5%) had TB disease; 1955 (37%) patients were not eligible for preventive therapy because they lived > 20 km away, had advanced HIV disease, or had previously had TB. Of 3366 who had a tuberculin skin test (TST) placed, 2548 (76%) had the TST read; 894 (35%) of these were positive. Of 506 persons who started treatment, 335 (66%) completed it. CONCLUSION: This unique program was feasible, detected a high proportion of undiagnosed TB, and successfully treated persons with latent infection. Expanding access to HIV VCT as well as collaboration between HIV/ AIDS and TB programs can increase the proportion of HIV-infected persons who can benefit from these programs.

PEPFAR support of alcohol-HIV prevention activities in Namibia and Botswana: a framework for investigation, implementation and evaluation.

BACKGROUND: The association between harmful use of alcohol and HIV infection is well documented. To address this dual epidemic, the US President's Emergency Plan for AIDS Relief (PEPFAR) developed and implemented a multi-pronged approach primarily in Namibia and Botswana. We present the approach and preliminary results of the public health investigative and programmatic activities designed, initiated and supported by PEPFAR to combat the harmful use of alcohol and its association as a driver of HIV morbidity and mortality from 2008 to 2013. APPROACH: PEPFAR supported comprehensive alcohol programming using a matrix model approach that combined the socio-ecological framework and the Alcohol Misuse Prevention and Intervention Continuum. This structure enabled seven component objectives: (1) to quantify harmful use of alcohol through rapid assessments; (2) to develop and evaluate alcohol-based interventions; (3) to promote screening programs and alcohol abuse resource services; (4) to support stakeholder networks; (5) to support policy interventions and (6) structural interventions; and (7) to institutionalize universal prevention messages. DISCUSSION: Targeted PEPFAR support for alcohol activities resulted in several projects to address harmful alcohol use and HIV. Components are graphically conceptualized within the matrix model, demonstrating the intersections between primary, secondary and tertiary prevention activities and individual, interpersonal, community, and societal factors. Key initiative successes included leveraging alcohol harm prevention activities that enabled projects to be piloted in healthcare settings, schools, communities, and alcohol outlets. Primary challenges included the complexity of multi-sectorial programming, varying degrees of political will, and difficulties monitoring outcomes over the short duration of the program.

Skeletal anchorage for everybody? a questionnaire study on frequency of use and clinical indications in daily practice.

AIM: The purpose of this survey was to determine how commonly, and in what clinical situations, German-based orthodontists use skeletal anchorage devices in daily clinical practice. METHOD: In early 2013, a set of questionnaires on the subject of skeletal anchorage devices was mailed to 2459 members of the German Orthodontic Society (Deutsche Gesellschaft für Kieferorthopädie, DGKFO). The questions dealt separately with mini screws (MSCs) and osseointegrated palatal implants (OPIs). The addresses were asked whether or not, as well as how frequently and in what clinical situations, they used these MSCs and/or OPIs, what their experience was, and to elaborate on their reasons for using or not using these devices. RESULTS: The rate of returned questionnaires was 48 %. To correctly interpret our data, it should be kept in mind that an unknown number of respondents did not distinguish between OPIs and palatally inserted MSCs. Overall, 62 % indicated that they did use MSCs and/or OPIs, although most of them (> 50 %) infrequently (≤ 2 new patients/3 months). Only ≤ 2 % were frequent users (> 2 new patients/week). While most users (> 70 %) indicated that their experience was mostly good, only ≤ 50 % considered the devices easy and trouble-free to use in daily clinical practice. The median percentage of insertion procedures conducted by the respondents themselves was 2 % for MSCs and 0 % for OPIs. Many of the non-users indicated that their treatment concept did not include suitable clinical indications (≥ 50 %), expressed skepticism about the success rates (56 % of MSC and 21 % of OPI non-users), or thought that the insertion procedures involved were too complex or time-consuming (33 % of MSC and 56 % of OPI non-users). CONCLUSION: A total of 62 % of German-based orthodontists participating in this survey indicated using skeletal anchorage devices, although most of them infrequently. Major reasons for non-use were lack of clinical indications, skepticism about the success rate of MSCs, and overly complex or time-consuming procedures of surgical OPI insertion.

Efficient parallel linear scaling construction of the density matrix for Born-Oppenheimer molecular dynamics.

We present an algorithm for the calculation of the density matrix that for insulators scales linearly with system size and parallelizes efficiently on multicore, shared memory platforms with small and controllable numerical errors. The algorithm is based on an implementation of the second-order spectral projection (SP2) algorithm [ Niklasson, A. M. N. Phys. Rev. B 2002 , 66 , 155115 ] in sparse matrix algebra with the ELLPACK-R data format. We illustrate the performance of the algorithm within self-consistent tight binding theory by total energy calculations of gas phase poly(ethylene) molecules and periodic liquid water systems containing up to 15,000 atoms on up to 16 CPU cores. We consider algorithm-specific performance aspects, such as local vs nonlocal memory access and the degree of matrix sparsity. Comparisons to sparse matrix algebra implementations using off-the-shelf libraries on multicore CPUs, graphics processing units (GPUs), and the Intel many integrated core (MIC) architecture are also presented. The accuracy and stability of the algorithm are illustrated with long duration Born-Oppenheimer molecular dynamics simulations of 1000 water molecules and a 303 atom Trp cage protein solvated by 2682 water molecules.

Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI.

SETTING: Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES: To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN: Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS: Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION: The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.