A low affinity penicillin-binding protein 2x is required for heteroresistance in Streptococcus pneumoniae

Heteroresistance to penicillin in Streptococcus pneumoniae is the ability of subpopulations to grow at a higher antibiotic concentration than expected from the minimal inhibitory concentration (MIC). This may render conventional resistance testing unreliable and lead to therapeutic failure. We investigated the role of the primary β-lactam resistance determinants, penicillin binding proteins PBP2b and PBP2x and secondary resistance determinant PBP1a in heteroresistance to penicillin. Transformants containing PBP genes from heteroresistant strain Spain(23F)2349 in non-heteroresistant strain R6 background were tested for heteroresistance by population analysis profiling (PAP). We found that pbp2x, but not pbp2b or pbp1a alone, conferred heteroresistance to R6. However, a change of pbp2x expression is not observed and therefore expression does not correlate with an increased proportion of resistant subpopulations. Additional ciaR disruption mutants which have been described to mediate PBP-independent β-lactam resistance revealed no heteroresistant phenotype by PAP.We also showed, that the highly resistant subpopulations (HOM*) of transformants containing low affinity pbp2x undergo an increase in resistance upon selection on penicillin plates which partially reverts after passaging on selection-free medium. Shotgun proteomic analysis showed an upregulation of phosphate ABC transporter subunit proteins pstS, phoU, pstB and pstC in these highly resistant subpopulations.In conclusion, the presence of low affinity pbp2x enables certain pneumococcal colonies to survive in the presence of beta lactams. Upregulation of phosphate ABC transporter genes may represent a reversible adaption to antibiotic stress.

Späte Scheidungen: Fakten, Gründe und Auswirkungen. Ein interdisziplinärer Blick auf Ergebnisse einer Schweizer Studie

Scheidungen im Alter sind eine zunehmende gesellschaftliche Realität, allerdings wurde dieses Phänomen bislang kaum wissenschaftlich untersucht. In diesem Beitrag werden neueste Forschungsergebnisse einer Schweizer Studie vorgestellt, welche zeigen, dass späte Scheidungen ein einschneidendes kritisches Lebensereignis mit multiplen Gründen und mannigfachen negativen Auswirkungen auf persönlicher, familialer und sozialer Ebene ist. Allerdings gibt es grosse individuelle Unterschiede, insbesondere Geschlechterunterschiede, hinsichtlich der Gründe und auch bezüglich der psychosozialen Adaptation. Das Ausleuchten der Forschungsresultate trägt nicht nur zu einem besseren Verständnis des Phänomens bei, sondern liefert auch Grundlagen für die familienrechtliche Praxis.

The Family Pasteurellaceae

This chapter describes the systematics and evolution of Pasteurellaceae with emphasis on new information generated since the 3rd edition of The Prokaryotes which only included chapters dealing with Haemophilus, Actinobacillus, and Pasteurella. A major source of new information for the current chapter has been provided by whole genome sequences now available for many taxa of the family. Some 100 species and species-like taxa have been documented and 18 genera of Pasteurellaceae reported so far. Members of the family include specialized commensals, potential pathogens, or pathogens of vertebrates and mainly survive poorly in other habitats including the external environment. The pathogenic members are of major importance to animal production and human health. Members of Pasteurellaceae have relatively small genomes, probably as a result of adaption to a special habitat. The most important species in veterinary microbiology include Pasteurella multocida, Actinobacillus pleuropneumoniae, [Haemophilus] parasuis, Mannheimia haemolytica, Bibersteinia trehalosi, and Avibacterium paragallinarum, while Haemophilus influenzae and Aggregatibacter actinomycetemcomitans represent the most important species as to human disease. Traditional isolation techniques are still used in both human and veterinary clinical diagnostic laboratories although genetically based diagnostic methods have replaced traditional biochemical/physiological methods for characterization and identification. For all species, MALDI-TOF can now be used as a diagnostic tool. As control and if MALDI-TOF equipment is not at hand, PCR-based specific detection is possible for Pasteurella multocida, Actinobacillus pleuropneumoniae, [Haemophilus] parasuis, Mannheimia haemolytica, Avibacterium paragallinarum, Gallibacterium anatis, Haemophilus influenzae, and Aggregatibacter actinomycetemcomitans. A lot of work has been directed towards identification of virulence factors and understanding host microbe interactions involved in disease.

The Freedom SOLO bovine pericardial stentless valve

Abstract: The third-generation bovine pericardium Freedom SOLO (FS) stentless valve emerged in 2004 as a modified version of the Pericarbon Freedom stentless valve and as a very attractive alternative to stented bioprostheses. The design, choice of tissue, and anticalcification treatment fulfill most, if not all, requirements for an ideal valve substitute. The FS combines the single-suture, subcoronary implantation technique with the latest-generation bovine pericardial tissue and novel anticalcification treatment. The design allows imitation of the native healthy valve through unrestricted adaption to the patient's anatomy, reproducing a normal valve/root complex. However, despite hemodynamic performance superior to stented valves, we are approaching a critical observation period as superior durability, freedom from structural valve deterioration, and nonstructural failure has not been proven as expected. However, optimal performance and freedom from structural valve deterioration depend on correct sizing and perfect symmetric implantation, to ensure low leaflet stress. Any malpositioning can lead to tissue fatigue over time. Furthermore, the potential for better outcomes depends on optimal patient selection and observance of the limitations for the use of stentless valves, particularly for the FS. Clearly, stentless valve implantation techniques are less reproducible and standardized, and require surgeon-dependent experience and skill. Regardless of whether or not stentless valve durability surpasses third-generation stented bioprostheses, they will continue to play a role in the surgical repertoire. This review intends to help practitioners avoid pitfalls, observe limitations, and improve patient selection for optimal long-term outcome with the attractive FS stentless valve.

What does professionalisation mean? Perceptions of professionalisation in swiss sport federations

Introduction: Organisational changes in sports federations are often associated with a drift from a volunteer driven to an increasingly business-like phenomenon (Shilbury & Ferkins, 2011). This process of transfor-mation is be called as “professionalization”. Accordingly, professionalization seems to be an appropriate strategy for sport organisations in order to meet organizational pressure due to challenges of a more complex and dynamic changing environment adequately. Despite the increasing research interest and the attempts for systematization on the phenomenon of professionalization it still remains unclear what does the term professionalization exactly mean (Dowling et al., 2014). Thus, there is a lack of a consistent concept of professionalization that is needed in order to explore different facets and perspectives of this phenomenon more validly. Against this background following question emerged: What is the suitable concept of professionalization for analyzing the actual ongoing processes of change, adaption or transformation in sport federations? Methods: Dealing with this question, following two-step approach was choosen: (1) In a first step a scholar’s perspective at professionalisation of sport organisations will be displayed in order to explore both the common ground as well as divergences and inconsistencies in previous approaches. Therefore, a literature review is indicated. (2) In a second step, and in contrast to previous studies we will consider a practical point of view by a so called second-order observation of experts to gain valuable insights into current thinking and acting towards professionalization in sport federations. In doing so, a hermeneutical approach is used, which is about understanding the meaning of contexts by grasping the everyday world, and draw insight and meaning from it (Shilbury et al., 2013). Accordance with hermeneutics, the explorative interpretive knowledge of expert interviews was used. The interviews were conducted with a sample of six selected experts, who have both dedicated insider knowledge and the overall view of all Swiss sport federations. Results and discussion: The summaries of literature review could be categorized into two research currents. The one defines professionalization as a structural process towards professional status of occupations. The other defines it in a broader sense as an organisational change towards a business-like approach. Whereas the first perspective there is a broad scientific consensus that second isn’t that clear, however. Explorative analysis of interview data reveals different themes in relation to professionalization of sports federation. First theme deals with a changed philosophy as more strategic alignment towards for-profit, efficiency and quality orientation. Second theme refers to paid work associated with more competence orientation and balanced governance between paid and voluntary work. Third theme deals with acting shift towards more rationalization and efficiency by implementation of innovative management and communication tools. Based on findings of both our review of scholar`s perspective as well insights from experts we will provide – in the sense of synthesis – a more clear understanding of what does professionalization mean that can be useful in terms of further studies. References: Dowling, M., Edwards, J. & Washington, M. (2014). Understanding the concept of professionalisation in sport management research. Sport Management Review, 17 (4), 520–529. Shilbury, D., Ferkins, L. & Smythe, L. (2013). Sport governance encounters: Insights from lived experiences. Sport Management Review, 16,349–363. Shilbury, D., & Ferkins, L. (2011). Professionalisation, sport governance and strategic capability. Managing Leisure, 16, 108–127.

Adaptation of career goals to self and opportunities in early adolescence

Development of career goals that are adapted to self and opportunities is a central component of adolescent career preparation. The present longitudinal study (conducted throughout the eighth grade with three assessment points) investigated how 330 Swiss adolescents simultaneously adapt career goals to interests, scholastic achievement and environmental opportunities. Results demonstrated that students increasingly adapt their goals to the environment. Mean adaptation to environment related positively to degree of adaption to interests and achievement. Increased adaptation to environment over time related to increased adaptation to achievement but to decreased adaptation to interests. Gender, attended school type and nationality moderated adaptation processes. Structurally disadvantaged students (girls, lower requirements school track, immigrant students) reported more conflict in aligning adaptation to environment with adaptation to interests.

The energy expenditure of 2 Holstein cow strains in an organic grazing system

Until recently, measurements of energy expenditure (EE; herein defined as heat production) in respiration chambers did not account for the extra energy requirements of grazing dairy cows on pasture. As energy is first limiting in most pasture-based milk production systems, its efficient use is important. Therefore, the aim of the present study was to compare EE, which can be affected by differences in body weight (BW), body composition, grazing behavior, physical activity, and milk production level, in 2 Holstein cow strains. Twelve Swiss Holstein-Friesian (HCH; 616 kg of BW) and 12 New Zealand Holstein-Friesian (HNZ; 570 kg of BW) cows in the third stage of lactation were paired according to their stage of lactation and kept in a rotational, full-time grazing system without concentrate supplementation. After adaption, the daily milk yield, grass intake using the alkane double-indicator technique, nutrient digestibility, physical activity, and grazing behavior recorded by an automatic jaw movement recorder were investigated over 7d. Using the (13)C bicarbonate dilution technique in combination with an automatic blood sampling system, EE based on measured carbon dioxide production was determined in 1 cow pair per day between 0800 to 1400 h. The HCH were heavier and had a lower body condition score compared with HNZ, but the difference in BW was smaller compared with former studies. Milk production, grass intake, and nutrient digestibility did not differ between the 2 cow strains, but HCH grazed for a longer time during the 6-h measurement period and performed more grazing mastication compared with the HNZ. No difference was found between the 2 cow strains with regard to EE (291 ± 15.6 kJ) per kilogram of metabolic BW, mainly due to a high between-animal variation in EE. As efficiency and energy use are important in sustainable, pasture-based, organic milk production systems, the determining factors for EE, such as methodology, genetics, physical activity, grazing behavior, and pasture quality, should be investigated and quantified in more detail in future studies.

Performing AIDS. The Film-maker Rosa von Praunheim between HIV/AIDS-Communities in Germany and the USA

The paper explores the works of German film-maker Rosa von Praunheim during the AIDS crisis, who worked in Germany and the USA in the 1980ies and 1990ies and produced several films portraying the gay communities in both countries in the face of AIDS. The first part of the paper analyses how von Praunheim’s films show different forms of performing community in the two countries. It discusses the filmic techniques utilized to criticize the reaction of the German gay community to the appearance of AIDS and to present Amercian traditions of forming and performing a community as a role model for AIDS-activism. The second part focuses on von Praunheim’s autobiography „40 Years of Perversity. The Sentimental Memoirs of Rosa von Raunheim“ (1993) and the rhetoric strategies he – being HIV-negative himself – uses to become part of New York’s HIV-community. The paper examines the hypothesis that von Praunheim’s rhetoric is constructing and performing a „participative identity“ (Alois Hahn). The paper finally discusses the use and adaption of terms and symbols originating from the context of German National Socialism (e.g. the pink triangle) within the process of forming and performing New York’s AIDS-Community and how they are reused and readapted by Rosa von Praunheim.

Fusion of fundus images and MRI data of the human eye

Purpose Ophthalmologists are confronted with a set of different image modalities to diagnose eye tumors e.g., fundus photography, CT and MRI. However, these images are often complementary and represent pathologies differently. Some aspects of tumors can only be seen in a particular modality. A fusion of modalities would improve the contextual information for diagnosis. The presented work attempts to register color fundus photography with MRI volumes. This would complement the low resolution 3D information in the MRI with high resolution 2D fundus images. Methods MRI volumes were acquired from 12 infants under the age of 5 with unilateral retinoblastoma. The contrast-enhanced T1-FLAIR sequence was performed with an isotropic resolution of less than 0.5mm. Fundus images were acquired with a RetCam camera. For healthy eyes, two landmarks were used: the optic disk and the fovea. The eyes were detected and extracted from the MRI volume using a 3D adaption of the Fast Radial Symmetry Transform (FRST). The cropped volume was automatically segmented using the Split Bregman algorithm. The optic nerve was enhanced by a Frangi vessel filter. By intersection the nerve with the retina the optic disk was found. The fovea position was estimated by constraining the position with the angle between the optic and the visual axis as well as the distance from the optic disk. The optical axis was detected automatically by fitting a parable on to the lens surface. On the fundus, the optic disk and the fovea were detected by using the method of Budai et al. Finally, the image was projected on to the segmented surface using the lens position as the camera center. In tumor affected eyes, the manually segmented tumors were used instead of the optic disk and macula for the registration. Results In all of the 12 MRI volumes that were tested the 24 eyes were found correctly, including healthy and pathological cases. In healthy eyes the optic nerve head was found in all of the tested eyes with an error of 1.08 +/- 0.37mm. A successful registration can be seen in figure 1. Conclusions The presented method is a step toward automatic fusion of modalities in ophthalmology. The combination enhances the MRI volume with higher resolution from the color fundus on the retina. Tumor treatment planning is improved by avoiding critical structures and disease progression monitoring is made easier.

Trajectories of psychological adaptation to marital breakup after a long-term marriage

Background: Marital dissolution is known to be among the most stressful life events with long- reaching negative consequences on individuals’ lives. A limitation in research to date is that most studies have focused on the impact of marital disruption on well-being outcomes in younger adults. Furthermore, although population-based studies on divorce document a broad range of negative effects, more fine-grained analyses reveal a large heterogeneity in people’s adjustment, which is still not well understood. Objective: To explore trajectories of psychological adaptation to marital breakup after a long-term marriage, and to examine variables accounting for recovery or chronicity in terms of intrapersonal resources (personality, trait resilience, personal growth), relationship variables (satisfaction with ex- relationship, length of marriage, time since divorce) and socio-demographic variables (age, gender, financial situation). Methods: Latent transition analysis is used to examine the course of psychological adaptation (i.e., depressive symptoms, life satisfaction, hopelessness, mourning and subjective health) to divorce over two years among five profiles of 308 divorcees (mean age: 55.6 years; average duration of former marriage: 23.62 years): Two larger groups of individuals, the one which adapted very well (‘resilients’, 29%), the other quite well (‘average copers’, 49%), and three groups with major difficulties (‘vulnerables’, 6%; ‘malcontents’, 12%; and ‘resigned’, 4%). In a second step the differences among transition patterns were explored on the basis of the distal variables (i.e., intrapersonal resources, relationship variables, socio-demographics). Results: Although the probability of upward changes was higher for those individuals with lower adaptation at time 1, only a small number of individuals made an upward change from the maladapted to the well-adapted groups throughout the two years. The groups of copers and resilients remained stable in their psychological adaption. The most consistent results related to upward changes were intrapersonal resources, namely the NEO personality traits and trait resilience. Conclusion: The majority of individuals divorcing after a long-term marriage adapt successfully over time. Adaptation trajectories depend primarily on intrapersonal resources. However, a minority of divorcees exhibit enduring difficulties. Knowledge about the diversity of these trajectories of vulnerability could be of great help for designing psychological interventions to better tackle this critical life event.

A Word. Palaver and Its Transferal Residues

The word 'palaver' is colloquially associated with useless verbiage and the nuisance of a tediously long, aimless and superfluous debate. At the same time, it insinuates an uncivilized culture of discourse beyond reason. Thus it appears to be of vaguely exotic origin but still firmly set in the European lexicon. Yet behind this contemporary meaning there lies a long history of linguistic and cultural transfers which is encased in a context of different usages of language and their intersections. By tracing the usage and semantics of 'palaver' in various encyclopaedias, glossaries and dictionaries of English, French, German, Portuguese and Spanish, the following article explores the rich history of this word. Moreover, it also regards the travelling semantics of the term 'palaver' as a process of cultural transfer that can be likened to the microcellular workings of a (retro)virus. Viral reproduction and evolution work through processes of transfer that enable the alteration of the host to adjust it to the replication and reproduction of the virus. In some cases, these processes also allow for the mutation or modification of the virus, making it suitable for transfer from one host to another. The virus is thus offered here as a vital model for cultural transfer: It not only encompasses the necessary adoption and adaption of contents or objects of cultural transfer in different contexts. It contributes to a conceptual understanding of the transferal residue that the transferred content is endowed with by its diversifying contexts. This model thereby surpasses an understanding of cultural transfer as literal translation or transmission: it conceptualizes cultural transfer as an agent of evolutionary processes, allowing for mutational effects of transfer as endowment.

THE DISCHARGED PSYCHIATRIC PATIENT: POST-HOSPITAL ADJUSTMENT AND FACTORS AFFECTING REHOSPITALIZATION

Discharged psychiatric patients were studied six months post-discharge to determine those demographic, social and clinical characteristics affecting positive or negative adjustment and the degree to which the use of mental health services and medication compliance mediated the effects. With the exception of those with primary or secondary diagnoses of OBS, substance abuse or mental retardation, sixty-three psychiatric subjects between the ages of eighteen and sixty-four were chosen from all admissions into the hospital and interviewed six months after discharge using a specially designed questionnaire.^ The subjects' adjustment to community living was found to be marginal. Although not engaged in destructive activities, over half were living with their family members who supported them financially and emotionally. Most were unemployed and had been so for a long time. Others worked sporadically and frequently changed residences. Most did have substantial social ties with extended family and with friends with whom they interacted regularly, but one-fourth were socially isolated. Almost three-quarters continued to obtain regular mental health services after discharge and followed medication instructions under the supervision of their physician. The use of mental health services after discharge and the use of medication did not appear to affect the subjects' community adaption or their rate of rehospitalization.^ Forty percent of those discharged were rehospitalized by the end of the follow-up period. Four levels of risk of rehospitalization emerged. The highest risk was associated with a history of five or more prior hospitalizations, living alone, and social isolation. One third or more of the subjects expressed a need for more counseling, leisure time activities, case-manager assistance, vocational guidance, supervised housing, and placement into a transitional residential treatment program.^ Recommendations were made to enhance the ability to predict recidivism, to develop interorganizational casework management programs linking the patient and family to the community mental health system and to create computerized tracking and monitoring programs that systematically report patient treatment regimen and progress cross-sectionally and longitudinally. ^

Modified 3+3 design for phase I clinical trials

Phase I clinical trial is mainly designed to determine the maximum tolerated dose (MTD) of a new drug. Optimization of phase I trial design is crucial to minimize the number of enrolled patients exposed to unsafe dose levels and to provide reliable information to the later phases of clinical trials. Although it has been criticized about its inefficient MTD estimation, nowadays the traditional 3+3 method remains dominant in practice due to its simplicity and conservative estimation. There are many new designs that have been proven to generate more credible MTD estimation, such as the Continual Reassessment Method (CRM). Despite its accepted better performance, the CRM design is still not widely used in real trials. There are several factors that contribute to the difficulties of CRM adaption in practice. First, CRM is not widely accepted by the regulatory agencies such as FDA in terms of safety. It is considered to be less conservative and tend to expose more patients above the MTD level than the traditional design. Second, CRM is relatively complex and not intuitive for the clinicians to fully understand. Third, the CRM method take much more time and need statistical experts and computer programs throughout the trial. The current situation is that the clinicians still tend to follow the trial process that they are comfortable with. This situation is not likely to change in the near future. Based on this situation, we have the motivation to improve the accuracy of MTD selection while follow the procedure of the traditional design to maintain simplicity. We found that in 3+3 method, the dose transition and the MTD determination are relatively independent. Thus we proposed to separate the two stages. The dose transition rule remained the same as 3+3 method. After getting the toxicity information from the dose transition stage, we combined the isotonic transformation to ensure the monotonic increasing order before selecting the optimal MTD. To compare the operating characteristics of the proposed isotonic method and the other designs, we carried out 10,000 simulation trials under different dose setting scenarios to compare the design characteristics of the isotonic modified method with standard 3+3 method, CRM, biased coin design (BC) and k-in-a-row design (KIAW). The isotonic modified method improved MTD estimation of the standard 3+3 in 39 out of 40 scenarios. The improvement is much greater when the target is 0.3 other than 0.25. The modified design is also competitive when comparing with other selected methods. A CRM method performed better in general but was not as stable as the isotonic method throughout the different dose settings. The results demonstrated that our proposed isotonic modified method is not only easily conducted using the same procedure as 3+3 but also outperforms the conventional 3+3 design. It can also be applied to determine MTD for any given TTL. These features make the isotonic modified method of practical value in phase I clinical trials.^

Distribution of marine invertebrate larvae in the southern Kara Sea (Russian Arctic)

Within the generally oligotroph Arctic marine environment river outlets are favoured by many planktonic and benthic organisms due to their high input of organic carbon. The retention of pelagic larvae within nursery grounds and/or the ability to return to their parental grounds prior to settlement is one important factor for the persistence of benthic communities in such river influenced areas. The southern Kara Sea is strongly controlled by high freshwater inputs from the Ob and Yenisei Rivers, which create a pronounced bi-layered pycnocline with a warm fresh/brackish water layer on top and a cold high saline marine layer below. The dispersal of five meroplanktonic species and settled juveniles (the brittle star Ophiocten sericeum, and the polychaetes Micronephtys minuta, Nereimyra aphroditoides, Phyllodoce groenlandica and Prionospio cirrifera) in relation to the adult distribution patterns was investigated. For all apart from P. cirrifera the highest densities of larvae were found in the upper brackish water layer. To assess size-at-settlement, the body sizes of larvae and newly settled juveniles were estimated and compared. Dispersal patterns ranged from virtually no adaption to river run-off as in the common, stenohaline O. sericeum and M. minuta (7 ind./m**3, 459 µm) to local retention as in N. aphroditoides (7 ind./m**3, 541 µm) and P. groenlandica (0.5 ind./m**3, 1121 µm) retained by horizontal eddies created by the outflow. Adults of P. cirrifera, which were exclusively restricted to the estuary of the Yenisei River, showed a well adapted reproductive behaviour to ensure a high retention potential of their progenies. The larvae (1.5 ind./m**3, 1513 µm) were only present in the lower water layers, most probably taking advantage of the prevailing near bottom counter current retaining them within their hatching areas.

(Table 1) Population density and biomass of the foraminifer Rupertina, and grain size of cores from the Norwegian continental slope

Rupertina stabilis occupies a depth restricted biotope of suspension feeding animals situated at the Norwegian continental margin. It extends from the Voring plateau northwards for at least 200 - 300 km, in depths between 600 and 800 m. This slope position is known for relatively strong bottom currents and shifting watermass boundaries. - The species is attached to hard substrates, mainly stones or hydroid stalks and obviously prefers an elevated position. It is building a permanent cyst of sponge spicules and debris at the apertural region. The spicules are used to support a pseudopodial network similar to that described from Halyphysema (LIPPS 1983). It is believed to serve as a filter apparatus. - A review of known occurences in the Atlantic is given, suggesting a temperature adaption of the species ranging from 0°C to a maximum of 8°C. Specimens were successfully cultured for about 2-3 weeks.