Introduction: The best method to assess the extension of pulmonary cysts in HRCT and whether it correlates with six-minute walk test (6MWT) variables, metalloproteinases (MMPs) or vascular endothelial growth factor-D (VEGF-D) dosage have not been defined in lymphangioleiomyomatosis (LAM). Objectives: To study the extension of pulmonary cysts in HRCT and to determine its correlations with pulmonary function tests, MMPs and VEGF-D dosage, the walking distance and dessaturation–distance ratio (DDR) in 6MWT in LAM (Pimenta, S.P. et al . Clinics 2010;65:841-6). Methods: Data from 23 women with LAM followed at the University of Sao Paulo were evaluated. The extension of pulmonary cysts in HRCT was assessed by computing the cyst volume over the entire lung volume. Spearman correlation coefficient was used to establish the association between the extension of cysts and the other variables. Results: The mean age was 46 ± 8 years. The extension of cysts in HRCT was 6.8% (median). Mean FEV1/FVC, FEV1, DLCO and RV/TLC were, respectively, 0.68 ± 0.19, 76 ± 25%pred, 65 ± 25%pred and 0.37 ± 0.08. The distance walked was 508 ± 112m, while the DDR was 4 (median). VEGF-D serum level was 464 (median) . The extension of cysts correlated best with DLCO (r=-0.82, p<0.0001), FEV1/FVC (r=-0.84, p<0.0001), RV/TLC (r=0.64, p<0.0001), and DDR (r=0.76, p<0.0001). A weak correlation was found with VEGF-D (r=0.45, p=0.03). There was no correlation with the walking distance or the level of MMPs. Conclusions: The severity of pulmonary cystic involvement was mild and correlated with airway obstruction, air trapping, DLCO, and DDR. The use of VEGF-D and MMPs to assess the severity of LAM remains controversial.


Physicians are ethically bound to maintain competence in their field as part of their professional accountability to the public. The Canadian Medical Association's Code of Ethics says it is the responsibility of physicians "to engage in lifelong learning to maintain and improve their professional knowledge, skills and attitudes."1 Despite this, no external verification of Canadian physicians' ongoing competence is required and, hence, the profession cannot prove to the public that it is ensuring the highest standards.

Currently, the processes for ensuring that physicians maintain their competence depend on the independent and heterogeneous regulatory decisions of each provincial College of Physicians and Surgeons. At present, 3 provinces (Saskatchewan, Ontario and Quebec) have mandated that physicians participate in an educational program to maintain their licence. Typically, this requirement is met by participation in the Royal College of Physicians and Surgeons' Maintenance of Certification program or the College of Family Physicians' Maintenance of Proficiency program. Although these programs address the right conceptual elements of maintaining competence, they are based on self-reporting and therefore lack rigour in holding physicians accountable. An alternative approach used in Alberta and Nova Scotia requires physicians to participate in a review process in which they are offered feedback from patients and peers about their performance. The program is designed to foster quality improvement, but it lacks an external standard for "passing." Moreover, the process is only feasible for primary care and larger specialties because it is hard to do peer review in specialties with few members.

Voices for change are now demanding a more transparent and accountable process to uphold professional standards. In 2007, a position paper by the Federation of Medical Regulatory Authorities of Canada stated that "all licensed physicians in Canada must participate in a recognized revalidation process in which they demonstrate their commitment to continued competent performance in a framework that is fair, relevant, inclusive, transferable and formative."2 It stated that the programs administered by the Royal College of Physicians and Surgeons and the College of Family Physicians provided a Canadian standards-based framework for professional development but that the programs lack evidence of whether physicians actually put their knowledge and skills into practice. Although the Federation of Medical Regulatory Authorities of Canada does not have the authority to implement changes, the broad support for this position paper from national medical organizations has put pressure on the provincial colleges to consider policy changes. Additionally, high-profile examples of serious breaches in medical practice standards by individual doctors, like the recent cases of pathology errors in New Brunswick and Newfoundland, raise legitimate media and public concerns about whether current scrutiny of physicians by their peers is sufficiently rigorous or whether external regulation is required. Furthermore, the bar is being raised elsewhere, while Canada is not keeping pace: other countries such as the United Kingdom and the United States have already implemented more demanding revalidation mechanisms than currently required by most Canadian provinces.

As a practising internist in Canada, I have participated in the Royal College's Maintenance of Certification program. Every year, I submit my credits for participating in continuing medical education activities, including attending lectures, answering clinical questions relevant to my practice and engaging in a self-assessment program. No one tests me to see what I have learned or whether I have put the knowledge into practice. In contrast, I recently participated in the American Board of Internal Medicine's Maintenance of Certification process and found it far more challenging and demanding. Since 1990, all specialists in the United States must recertify every 10 years to continue to call themselves a certified specialist. The process requires participation in 2 components that are absent in Canada: a practice-improvement exercise and a secure examination. The practice-improvement module includes collecting data on actual practice performance in a particular area (e.g., diabetes management), assessing the office organization that supports care, and surveying patients to understand their experience. These data are submitted to the American Board of Internal Medicine, and physicians receive feedback compared with established standards and their peers. Physicians must also submit a quality-improvement plan. The secure examination is a computerized multiple choice test of cognitive skills in the field of practice. To prepare for the secure exam portion, I used a knowledge self-assessment program to review all of general internal medicine. Both the practice improvement and the preparation for the examination required significantly more sweat equity than the Royal College's process. I studied for 4 months and was worried that I would fail. I would never have made the effort if not faced with an examination.

Should we all have to pass an examination at periodic intervals? Evidence shows that the public supports the idea of regular knowledge examination of physicians. One survey reported 87% of patients believe this should occur.3 Furthermore, there is evidence that scores on a test can be an indicator of performance. In Quebec, investigators found that family physicians' scores on their certification examination and Medical Council of Canada Qualifying Examination were related to provision of quality care after 4–7 years in practice.4 More recently, Holmboe and colleagues found that physicians' scores on the American Board of Internal Medicine's Maintenance of Certification examination was associated with higher rates of performance in care for Medicare patients.5 Although cognitive knowledge tested with examinations is not the only measure of competence, it is an important dimension of accurate diagnosis and clinical decision-making. Undoubtedly, there is a need for more research to understand the relation between revalidation and quality of care in practice and to explore the most effective methods to assess physicians' maintenance of skills, knowledge and attitudes.

Canadian physicians and the provincial colleges should implement revalidation for all physicians. The standards must include an external assessment of physician competence, rather than relying exclusively on self-assessment. Some form of rigorous external testing is needed to make physicians work to meet the bar. Although further evidence is needed to determine the best process of revalidation, the process should include an external assessment of both medical knowledge and the actual ability of physicians to implement quality care in their practice. A secure examination, like in the United States, could assess knowledge, and a practice review with input from peers and patients could assess actual performance. National standards should delineate the minimum requirements.

Physicians will inevitably have concerns about the implications of raising the bar, including fears of failure, the burden of preparing and the possible effect of losing some physicians who do not pass from the workforce. However, these concerns would likely be transient. In the United States, recertification programs were met with initial resistance from physicians, but revalidation is now the expectation of all new graduates. Ultimately, we must be able to assure our colleagues and the public that we are living up to our professional responsibility of self-regulation and protecting the public's trust in our health care system.

Wendy Levinson MD Sir John and Lady Eaton Professor and Chair Department of Medicine University of Toronto Toronto, Ont.


Two dimensional (2D) nanostructures such as graphene have been attracting increasing research interest in the recent past due to their superior material properties. Herein, we report a facile and scalable method for the production of a few layered graphene sheets and the synthesis of TiO2 nanoparticles on the surface of the prepared graphene sheets using a single step hydrothermal method. The composites prepared with different graphene loading were assessed for their photocatalytic degradation ability under visible light and in dye sensitized solar cells (DSC). The results showed that the average thickness of the obtained graphene sheets was 1.1 nm and the TiO2 nanoparticles were uniformly dispersed on the surface of the graphene. In the photodegradation of methyl orange (MO), the photoactivity of the composite (with 10 wt% graphene loading) was found to be three times better than bare TiO2 nanoparticles. This increased activity is due to the synergistic effects of TiO2 nanoparticles and graphene sheets. For DSC, composites with 0.7 wt% graphene loading showed a maximum efficiency of 4.26%, 25% higher than without graphene.


Objective: The salivary gland tumors or otherwise called the "unusual tumors" are aptly named. The aim of this study was to determine the types, frequency, distribution, and demographic characteristics and treatment–outcome aspects of salivary gland tumors in a large representative sample from southern peninsular India. Thereby, an attempt was made to understand to why are they actually called unusually presenting usual tumors. Materials and Methods: This original article is a retrospective study regarding a 17-year single institutional experience of these tumors with yet again unusual patterns of presentations. This work was harvested from an oncological unit in the southern part of India, the Royapettah Govt Hospital. Medical records from 2002 to 2019 of salivary gland tumor patients were compiled to derive the data and analyzed. Statistical Analysis Used: The data were grouped and analyzed using simple measures of central tendency, percentages, and represented in tables and graphs. Results: There are some similarities but more dissimilarities with respect to their presentation. Males outnumbered females. Malignant tumors outnumbered benign tumors. However, the most common benign and malignant tumors were similar to the rest of the world. Conclusion: A much confluent and in-depth analysis from other parts of India as well as other regions of the Asian subcontinent and world needs to be done to understand the behavior of these usual tumors presenting unusually.


Various geochemical proxies are used to constrain the diagenetic origin and evolution of ancient dolomites. Dolomite stoichiometry (mole % MgCO3) and cation ordering, two mineralogical attributes that define dolomite, have also been shown to demonstrate utility in this regard. Observations from laboratory experiments and field studies suggest that these attributes broadly reflect the fluid chemistry and temperature of the dolomitizing environment. The degree to which these parameters reflect global conditions during dolomitization (e.g., seawater chemistry, eustasy, atmospheric pCO2) and long-term geological processes is poorly understood, however. Here, a large dataset consisting of mineralogical data from over 1,690 Phanerozoic dolomites from various geographic locations, stratigraphic ages, platform types, and depositional environments are queried to investigate the broader geological controls on dolomite stoichiometry and cation ordering in dolomites formed by early, near-surface dolomitization. A suite of statistical analyses performed on the global dataset indicate: 1) despite wide ranges at the eon, period, and epoch level, dolomite stoichiometry and cation ordering broadly increase with geologic age; 2) significant variations in dolomite stoichiometry and cation ordering throughout the Phanerozoic do not correlate with global parameters, such as seawater chemistry, eustasy, orogenic events, and ocean crust production; 3) dolomites associated with restricted depositional settings, such as restricted lagoons, and the intertidal and supratidal zones, are more stoichiometric than dolomites associated with open marine settings, such as the deep-subtidal and shallow-subtidal zones; and 4) dolomites from shallow ramps and epeiric carbonate platforms are generally more stoichiometric than dolomites from open shelves and isolated carbonate platforms. These observations permit a number of inferences to be drawn. First, the principal signal observed in the data is that local environmental conditions associated with platform type and depositional setting are the strongest control on dolomite mineralogy. The observation that more stoichiometric dolomites correlate with shallow and restricted depositional environments is consistent with laboratory experiments that show environmental factors, such as higher Mg:Ca, temperature, and salinity of the dolomitizing fluids yield more stoichiometric dolomite. Second, a weaker secondary signal is also observed such that dolomite stoichiometry and cation ordering both increase with geologic age, suggesting that progressive recrystallization driven by mineralogical stabilization during burial is also occurring. Collectively, these data suggest that spatial and temporal variations in stoichiometry and cation ordering reflect the interplay between local dolomitizing conditions near the surface and long-term mineralogical stabilization during burial.


Large concrete structures need to be inspected in order to assess their current physical and functional state, to predict future conditions, to support investment planning and decision making, and to allocate limited maintenance and rehabilitation resources. Current procedures in condition and safety assessment of large concrete structures are performed manually leading to subjective and unreliable results, costly and time-consuming data collection, and safety issues. To address these limitations, automated machine vision-based inspection procedures have increasingly been proposed by the research community. This paper presents current achievements and open challenges in vision-based inspection of large concrete structures. First, the general concept of Building Information Modeling is introduced. Then, vision-based 3D reconstruction and as-built spatial modeling of concrete civil infrastructure are presented. Following that, the focus is set on structural member recognition as well as on concrete damage detection and assessment exemplified for concrete columns. Although some challenges are still under investigation, it can be concluded that vision-based inspection methods have significantly improved over the last 10 years, and now, as-built spatial modeling as well as damage detection and assessment of large concrete structures have the potential to be fully automated.


Abstract The biological carbon pump (BCP) is the process by which ocean organisms transfer carbon from surface waters to the ocean interior and seafloor sediments for sequestration. Viruses are thought to increase the efficiency of the BCP by fostering primary production and facilitating the export of carbon-enriched materials in the deep sea (the viral "shunt and pump"). A prior study using an oligotrophic ocean-dominated dataset from the Tara Oceans expedition revealed that bacterial dsDNA viruses are better associated with variation in carbon export than either prokaryotes or eukaryotes, but eukaryotic viruses were not examined. Because eukaryotes contribute significantly to ocean biomass and net production (> 40%), their viruses might also play a role in the BCP. Here, we leveraged deep-sequencing molecular data generated in the framework of Tara Oceans to identify and quantify diverse lineages of large dsDNA and smaller RNA viruses of eukaryotes. We found that the abundance of these viruses explained 49% of the variation in carbon export (compared with 89% by bacterial dsDNA viruses) and also substantially explained the variation in net primary production (76%) and carbon export efficiency (50%). Prasinoviruses infecting Mamiellales as well as Mimivirus relatives putatively infecting haptophytes are among the eukaryotic virus lineages predicted to be the best contributors to BCP efficiency. These findings collectively provide a first-level window into how eukaryotic viruses impact the BCP and suggest that the virus-mediated shunt and pump indeed plays a role.


the mean score of tract dilation was 0 in group A vs. 9.9 in group (p[0), the mean score of lithotripsy skill was 0 in group A vs. 9.64 in group B (p<0.05), the mean score of nephrostomy tube placement was 8.0 in group A vs. 9.88 in group B (p<0.05), the mean score of skills at ureteral stent insertion was 9.0 in group A vs. 0 in group B (p<0.05), the mean score kidney anatomy evaluation using X-ray imaging was 8,6 in group A vs. 9.85 in group B (p<0.05), the mean score of tissue model feet back was 6.40 in group A vs. 9.96 in group B (p<0.05), the mean score of post-training errors discussion was 7.70 in group A vs. 9.94 in group B (p<0.05). The Mann-Whitney U-test showed that there was no a significant difference among both groups (U[16, p<0.05). CONCLUSIONS: The developed 3D-printed PCNL model is a novel, highly effective tool to facilitate enhanced endourological education.


Abstract Background The Economist Intelligence Unit takes a strategic approach to understand the impact of policy on lung cancer. Recommendations from our research, sponsored by MSD, will assist countries to improve systemic responses because outcomes remain poor and costs remain high despite scientific progress. Methods Our research centres on 13 countries: Austria, Belgium, Finland, France, Germany, Greece, Netherlands, Norway, Poland, Romania, Spain, Sweden, and the UK. Our literature review drew evidence from internationally-recognised sources and falls into 5 domains operationalised by 17 indicators assessing performance across the entire patient journey. After consultation with European experts, we populated our scorecard comparing policy and practice, examining service delivery, systems, access, financing and governance. Examination of preliminary findings in country workshops with clinicians, patient organisations and other key stakeholders enabled us to obtain nuanced information providing a clearer grasp on care than obtained from desk research alone. Results While patches of good practice exist, no country scores highly across all of our measurements. All but one country has a national cancer control plan: 75% are over five years old and do not incorporate recent oncological innovations. Clinical guidelines lack details on accelerating suspected lung cancer patients for diagnosis, referral pathways to secondary/tertiary care, supportive/palliative care, shared decision-making and psychological support within a specified time. Cancer registries exist in each country, yet clinicians report that clinically-focused cancer registries could house important information. Only 5 countries reimburse all four commonly used biomarkers for lung cancer. Conclusions Room for improvement in lung cancer policy exists across all the countries and domains we have studied. Our workshops ensured we focus on the most important opportunities for improving the delivery of lung cancer care relevant for each country. Now, based on the recommendations coming out of the research and agreed upon by stakeholders, we are in the policy development phase of our work where our goal is to assist policymakers improve care for people living with lung cancer in Europe. Legal entity responsible for the study The authors. Funding MSD. Disclosure All authors have declared no conflicts of interest.


This article was motivated by two of the major challenges which I believe congregations are facing within  the context of ministry, namely postmodernity and globalization. After seeking a fuller description of these two challenges I sought  a theological orientation within such a context (postmodern global village) as well as an ecclesiological  praxis that could be transformative and redemptive within such a context. I  believe to have found in the narrative orientation an appropriate way for doing theology in the postmodern context. The climax of this journey (story) is in the fusion of horizons between the theory-laden questions of descriptive theology and  the historical texts of the Christian faith within the narrative orientation. I discovered that truly transformative and redemptive praxis is only possible within  language communities  narrative communities). These narrative communities cannot exist in isolation, but are continuously confronted and relativised by the stories of other communities in the global village and therefore these language communities need to be open to the fragmentation and pluralism of the global village, otherwise they will not be able to respond to the reality of the globalization and postmodernity. The narrative communities needed a story (sacred story) that did not deny the reality  of fragmentation  and pluralism, but could incorporate this reality into its story. I found this story in the story of the cross and  therefore refer to the narrative communities as communities  of  and under the cross  of Christ. These ideas formed the basis for a transformative praxis within a specific congregation, namely Pastoral Redemptive Communities. These narrative communities are not an answer to the postmodern global village, but they do offer a way of proclaiming Christ crucified and allowing the deconstruction of the cross to create a community which is a redemptive alternative to the reality of the postmodern global village. This journey was a critical journey in dialogue with other disciplines (economics, philosophy, psychology and sociology) thereby opening it up for further dialogue within these other sciences as well as dialogue with other religious communities.


We have had over a year's experience now with the Lucas monitor/dialysate proportioning system and been very pleased with its operation, granting, of course, that the machine is well and properly understood. Recently we have also been very pleased with the performance of the Baxter "Ultraflo " coil used in the newest model of the Travenol R.S.P. machine, and it seemed obvious to marry the two together. Thus we have built a container capable of holding the " Ultraflo" coil, providing a continuous flow of dialysate through the coil at high rates of flow and under an adjustable negative pressure so as -to make use of the Lucas monitor system. This prototype canister, made of Perspex, is functioning well, producing perfectly normal dialyses with good end biochemical figures, and achieving these results within a period of between six and eight hours.


The CDK5 kinase regulatory subunit-associated protein 3 (CDK5RAP3 or C53/LZAP) regulates apoptosis induced by genotoxic stress. Although CDK5RAP3 has been implicated in cancer progression, its exact role in carcinogenesis is not well established. In this article, we report that CDK5RAP3 has an important prometastatic function in hepatocarcinogenesis. An examination of human hepatocellular carcinoma (HCC) samples revealed at least twofold overexpression of CDK5RAP3 transcripts in 58% (39/67) of HCC specimens when compared with corresponding nontumorous livers. CDK5RAP3 overexpression was associated with more aggressive biological behavior. In HCC cell lines, stable overexpression of CDK5RAP3 promoted, and small interfering RNA-mediated knockdown inhibited, tumorigenic activity and metastatic potential. We found that overexpression of CDK5RAP3 and p21-activated protein kinase 4 (PAK4) correlated in human HCCs, and that CDK5RAP3 was a novel binding partner of PAK4, and this binding enhanced PAK4 activity. siRNA-mediated knockdown of PAK4 in CDK5RAP3-expressing HCC cells reversed the enhanced cell invasiveness mediated by CDK5RAP3 overexpression, implying that PAK4 is essential for CDK5RAP3 function. Taken together, our findings reveal that CDK5RAP3 is widely overexpressed in HCC and that overexpression of CDK5RAP3 promotes HCC metastasis through PAK4 activation.


In a previous study [1] on vowel rounding anticipatory perception through a fricative consonant stream with a gating paradigm, we discovered that auditory information could be, in this VCV frame, ahead of visual information, and even of audiovisual information (hence A>AV>V). We propose here to extend this experiment to different modality-impaired groups of adults and children, namely: (i) to blind and impaired-hearing adults vs. normal hearing and sighted ones; (ii) and to impaired-hearing vs. normal hearing children (7-11year-old). Blind and sighted adults had globally comparable results in the auditory modality, though individually less categorical for the blind. In the visual condition, hearingimpaired adults had the same delayed performance as normal. In addition the same hearing-impaired adults were tested when practicing French Cued Speech (CS). Their performance indicated clearly that, with CS, they succeeded in the identification task as precociously as normal hearing in the auditory condition. Normal hearing children obtained the same ranking in their perceptual modalities, i.e. A>AV>V, but with a global delay of 20-30 ms compared to adults. Hearingimpaired children obtained again an anticipatory gain with CS comparable to the audio of normal children. The conclusion is that each group takes the best advantage of the natural timing of their available sensory modalities, by the face, the hand and the ear. For Cued Speech coders, the hand-to-face coordination can clearly substitute in time to the ear.


Object-based video representations are considered to be useful for easing the process of multimedia content production and enhancing user interactivity in multimedia productions. Object-based video presents several new technical challenges, however.

Firstly, as with conventional video representations, compression of the video data is a
requirement. For object-based representations, it is necessary to compress the shape of
each video object as it moves in time. This amounts to the compression of moving
binary images. This is achieved by the use of a technique called context-based
arithmetic encoding. The technique is utilised by applying it to rectangular pixel blocks and as such it is consistent with the standard tools of video compression. The blockbased application also facilitates well the exploitation of temporal redundancy in the sequence of binary shapes. For the first time, context-based arithmetic encoding is used in conjunction with motion compensation to provide inter-frame compression. The method, described in this thesis, has been thoroughly tested throughout the MPEG-4 core experiment process and due to favourable results, it has been adopted as part of the MPEG-4 video standard.

The second challenge lies in the acquisition of the video objects. Under normal conditions, a video sequence is captured as a sequence of frames and there is no inherent information about what objects are in the sequence, not to mention information relating to the shape of each object. Some means for segmenting semantic objects from general video sequences is required. For this purpose, several image analysis tools may be of help and in particular, it is believed that video object tracking algorithms will be important. A new tracking algorithm is developed based on piecewise polynomial motion representations and statistical estimation tools, e.g. the expectationmaximisation method and the minimum description length principle.


The expressive power of Gaussian processes depends heavily on the choice of kernel. In this work we propose the novel harmonizable mixture kernel (HMK), a family of expressive, interpretable, non-stationary kernels derived from mixture models on the generalized spectral representation. As a theoretically sound treatment of non-stationary kernels, HMK supports harmonizable covariances, a wide subset of kernels including all stationary and many non-stationary covariances. We also propose variational Fourier features, an inter-domain sparse GP inference framework that offers a representative set of 'inducing frequencies'. We show that harmonizable mixture kernels interpolate between local patterns, and that variational Fourier features offers a robust kernel learning framework for the new kernel family.


Crustal evolution is currently governed by plate tectonics and it has been shown that between the Archean and the Phanerozoic major changes in subduction styles occured. Among others, the chemistry of different plutonic rocks through time and the understanding of their petrogeneses have helped to define different stages in the evolution of plate tectonics. An important change around 2.7 Ga led to the formation of magmas within a metasomatized mantle: the sanukitoids. This diachronous event is interpreted as the result of the evolution from a shallow to a steep subduction style. Similar rocks are generated in the modern Earth, for example the Caledonian (Palaeozoic) high Ba-Sr plutons in northern Scotland [1]. In this contribution, we aim to study this Caledonian sanukitoid-like suite and test the reliability of several isotopic systems within the abundant accessory minerals. Whole rock chemistry (including radiogenic and stable isotopes) is well constrained. We now present a multi-isotope study of three accessory minerals (titanite, zircon and apatite). New Sm-Nd in-situ isotopes in titanite and apatite and Hf in zircon results are discussed in the light of oxygen isotopes previously published on the same samples for all phases [2]. These data are then compared to previous WR data obtained on the same samples[3], [4].


Cervical cancer is a leading cause of cancer death for women in low-resource settings. The World Health Organization recommends that cervical cancer screening programs incorporate HPV DNA testing, but available tests are expensive, require laboratory infrastructure, and cannot be performed at the point-of-care. We developed a two-dimensional paper network (2DPN), hybrid-capture, signal amplification assay and a point-of-care sample preparation protocol to detect high-risk HPV DNA from exfoliated cervical cells within an hour. The test does not require expensive equipment and has an estimated cost of < $3 per test without the need for batching. We evaluated performance of the paper HPV DNA assay with short synthetic and genomic HPV DNA targets, HPV positive and negative cellular samples, and two sets of clinical samples. The first set of clinical samples consisted of 16 biobanked, provider-collected cervical samples from a study in El Salvador previously tested with careHPV and subsequently tested in a controlled laboratory environment. The paper HPV DNA test correctly identified eight of eight HPV-negative clinical samples and seven of eight HPV-positive clinical samples. We then performed a field evaluation of the paper HPV DNA test in a hospital laboratory in Mozambique. Cellular controls generated expected results throughout field testing with fully lyophilized sample preparation and 2DPN reagents. When evaluated with 16 residual self-collected cervicovaginal samples previously tested by the GeneXpert HPV assay ( " Xpert " ), the accuracy of the HPV DNA paper test in the field was reduced compared to testing in the controlled laboratory environment, with positive results obtained for all eight HPV-positive samples as well as seven of eight HPV-negative samples. Further evaluation showed reduction in performance was likely due in part to increased concentration of exfoliated cells in the self-collected clinical samples from Mozambique compared with provider-collected samples from El Salvador. Finally, a formal usability assessment was conducted with users in El Salvador and Mozambique; the assay was rated as acceptable to perform after minimal training. With additional optimization for higher cell concentrations and inclusion of an internal cellular control, the paper HPV DNA assay offers promise as a low-cost, point-of-care cervical cancer screening test in low-resource settings.


In this article a high performance Extended Kalman filter algorithm is used to estimate rotor speed, rotor position and load torque in a Hybrid Stepper Motor (HSM). Together with a PI speed controller, the Kalman filter forms a very robust sensorless closed loop system. During acceleration the motor is capable of running in closed loop from 0-100% of the nominal speed. The controller can handle charge steps of over 50% of the maximum load torque, and acceleration up to 13 [krad/s/sup 2/]. To achieve theses good dynamic capabilities, the Kalman filter is optimized by an off-line identification process. This gives a very good match between the model and the real system. The standstill position at start-up is estimated by a current injection method. Due to the optimized Kalman filter the experimental results show very good precision and closed loop robustness for a 10.5 [W] HSM. The algorithm is implemented on a floating point DSP. The driver consists of two H-bridges with MOSFET transistors. The currents are measured with one shunt resistor for each phase.


PurposeThe purpose of this paper is to examine whether and how a methodological coupling of visualisations of trace data and interview methods can be utilised for information practices studies.Design/methodology/approachTrace data visualisation enquiry is suggested as the coupling of visualising exported data from an information system and using these visualisations as basis for interview guides and elicitation in information practices research. The methodology is illustrated and applied through a small-scale empirical study of a citizen science project.FindingsThe study found that trace data visualisation enquiry enabled fine-grained investigations of temporal aspects of information practices and to compare and explore temporal and geographical aspects of practices. Moreover, the methodology made possible inquiries for understanding information practices through trace data that were discussed through elicitation with participants. The study also found that it can aid a researcher of gaining a simultaneous overarching and close picture of information practices, which can lead to theoretical and methodological implications for information practices research.Originality/valueTrace data visualisation enquiry extends current methods for investigating information practices as it enables focus to be placed on the traces of practices as recorded through interactions with information systems and study participants' accounts of activities.


This book sets forth a new approach to twenty-first-century criminal justice and punishment, an approach that fully involves the community and provides a better way to make our criminal process more transparent and inclusive. The American criminal justice system faces numerous challenges because of its ongoing failure to integrate the community's voice. Using the lens of the Sixth Amendment jury trial right, this book offers fresh and much-needed ways for incorporating the citizenry into the procedures of criminal justice, resulting in greater investment and satisfaction in the system. Ultimately, the people's right to participate in the criminal justice system through the criminal jury – a right that is all too often overlooked – is essential to truly legitimizing the criminal process and ensuring its democratic nature.


OBJECTIVE Although patients with diabetic peripheral neuropathy (DPN) are more likely to fall than age-matched controls, the underlying causative factors are not yet fully understood. This study examines the effects of diabetes and neuropathy on strength generation and muscle activation patterns during walking up and down stairs, with implications for fall risk. RESEARCH DESIGN AND METHODS Sixty-three participants (21 patients with DPN, 21 diabetic controls, and 21 healthy controls) were examined while walking up and down a custom-built staircase. The speed of strength generation at the ankle and knee and muscle activation patterns of the ankle and knee extensor muscles were analyzed. RESULTS Patients with neuropathy displayed significantly slower ankle and knee strength generation than healthy controls during stair ascent and descent (P < 0.05). During ascent, the ankle and knee extensor muscles were activated significantly later by patients with neuropathy and took longer to reach peak activation (P < 0.05). During descent, neuropathic patients activated the ankle extensors significantly earlier, and the ankle and knee extensors took significantly longer to reach peak activation (P < 0.05). CONCLUSIONS Patients with DPN are slower at generating strength at the ankle and knee than control participants during walking up and down stairs. These changes, which are likely caused by altered activations of the extensor muscles, increase the likelihood of instability and may be important contributory factors for the increased risk of falling. Resistance exercise training may be a potential clinical intervention for improving these aspects and thereby potentially reducing fall risk.


A hydride tungsten complex, [WH2(η2-OOCCH3)(Ph2PCH2CH2PPh2)2][BPh4], was entrapped in the interlayer of a pillared layered clay (PILC) and in NaY zeolite. The adsorption of the complex in the liquid phase was the immobilization process used. The free complex and the new materials were characterized by several techniques: structural analysis by DRX, nitrogen adsorption isotherms and spectroscopic methods (ICP-AES, FTIR and UV/Vis). Analysis of the data indicates that the tungsten(IV) complex is immobilized in the host microporous structures, and exhibit structural properties that are different from those of the free complex. These differences could arise either from distortions caused by steric effects imposed by the structures or from interactions with the host matrix.


Short-term effects of air pollution (consisting primarily of sulphur dioxide and particulate matter but with low acidity) on respiratory morbidity were studied in asthmatic children from Sokolov, Czech Republic. Eighty nine children with asthma, who recorded daily peak expiratory flow measurements, symptoms and medication use in a diary, were analysed for 7 months during the winter of 1991-1992. Air pollution measurements included: SO2, total suspended particulates (TSPs), inhalable particles, ie. particulate matter of aerodynamic diameter < or = 10 microm, particle strong acidity (PSA) and fine particle sulphate concentration (SO4). Linear and logistic regression analyses estimated the impact of air pollutants adjusted for trend, temperature and weekend and autocorrelated errors. Exposure to elevated levels of air pollution was associated with decreased peak expiratory flow rates, increased respiratory symptoms, increased prevalence of school absence and fever, and increased medication use. Prolonged exposure to particle SO4 showed the largest effect estimates. At the end of January, an air pollution episode occurred, during which respiratory symptoms, prevalence of fever, school absence and asthma medication increased. The association between respiratory symptoms and particulate SO4 was highly dependent on this episode, whilst the associations between lung function and SO4 as well as between fever and SO4 were still observed when this air pollution episode was excluded. Some evidence was found that exposure to air pollution might have enhanced the respiratory symptoms while children were experiencing respiratory infections. In this study, a panel of children with mild asthma experienced small decreases in peak expiratory flow and increased dyspnoea in association with fine particles formed during air pollution episodes.


Digital innovation is bringing a great deal of change to industry, the economy and society. Radical transformations are being seen in the way these fields are organized, in their products and uses. Institut Mines-Telecom has always had a very close and privileged relationship with the economic and industrial world. IMT plays a major role in research partnerships and innovation, and support for economic development. The Industry of the Future is a strategic priority for IMT in facing future challenges and accompanying companies in their transitions. As a founding member of the Alliance for the Industry of the Future, IMT's unique position at the crossroads between industry and the digital world allows it to comprehend ruptures involving both the changes to processes and industrial management modes, and the digital tools involved. Although it is well known that a great deal of the potential effectiveness of digital technology lies in this joint transformation of our working methods and tools, the impact of this technology on the transformation of companies remains an active field of research. With vision and action based on the Training-Research-Innovation continuum, IMT is involved on all three levels of this major transition. As well as confronting the great challenges of more effective, safe, economical and flexible technologies, the Institute is extensively involved in this transition, imagining new organization models for companies, new products and services, new economic models, without forgetting the changing place of humans in industrial and organizational processes, along with new jobs and skills. This white paper, written under the supervision of Madeleine Besson, presents the current concern over the challenges of digital transformation for the company of the future. What will be the changes to companies' processes and business models? How will the notion of value creation change? What impact will this transformation have on the role of humans in companies? These questions, along with other equally pertinent ones, are studied by experts at IMT, questioning the very notion of the company and the meaning of its traditional links (design, production, use, the customer, value...) To understand the impacts and formalize the challenges of research for the company of the future in a relevant way, we must have a solid grasp of digital transformation. Technical, economic, human and societal responsibility aspects must be analyzed in order to find the integrated, transversal approach, which is essential to relevant and effective reflection over this complex, multi-faceted matter. These reflections must also take an historical approach. In this respect, the "ecosystemic" analysis proposed by Thierry Isckia sheds light on the changes that digital technology has imposed, at the same time noting the importance of the strategic dimension. Regarding future changes, Godefroy Dang Nguyen suggests some transformational leads that the digital world offers, in particular the new forms of cooperation providing a source of significant change to the institutional framework. The question of entrepreneurship in 2050, asked by Daniel Kaplan, provides the opportunity to open the field of study to include the changes in the structuring element of a company in the face of ecological and environmental transition, as well as transgenerational transition. Climate change and the ageing population are challenging the traditional determiners of progress and well-being. Finally, this white paper questions the very idea of the company itself, and the meaning of all of the traditional links in value creation. It provides the curious reader with several entry points to understanding the challenges of digital transformation for the future company, and certain key areas for reflection on this matter, which keeps gaining in speed and intensity.


Objective: Punarnavashtak kwath (PNK) is a classical Ayurvedic formulation, mentioned in Ayurvedic literature Bhaishajya Ratnavali, for hepatic disorders and asthma. This study investigated the hepatoprotective activity of PNK to validate the traditional use of this formulation. Materials and methods: PNK was prepared in the laboratory according to the method given in Ayurvedic literature. Phytochemical screening was performed to determine the presence of phytoconstituents. Hepatoprotective activity was evaluated against CCl4-induced hepatotoxicity in rats and by its effect on the HepG2 cell line. Results: Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins, and a bitter principle in PNK. Administration of PNK produced significant hepatoprotective effect as demonstrated by decreased levels of serum liver marker enzymes such as aspartate transaminase, serum alanine transaminase, serum alkaline phosphatase, and serum bilirubin and an increase in protein level. Thiopentone-induced sleeping time was also decreased in the PNK-treated animals compared with the CCl4-treated group. It also showed antioxidant activity by increase in activity of glutathione, superoxide dismutase, and catalase and by a decrease in thiobarbituric acid reactive substance level compared with the CCl4-treated group. Results of a histopathological study also support the hepatoprotective activity of PNK. Investigation carried out on the HepG2 cell line depicted significant increase in viability of cells exposed to PNK as compared with CCl4-treated cells. Discussion and Conclusion: It can be concluded that PNK protects hepatocytes from CCl4-induced liver damages due to its antioxidant effect on hepatocytes. An in vitro study on HepG2 cell lines also supports its protective effect.


Wind tunnel tests are generally obstructed by model support with limitations. The development of magnetic suspension wind tunnel (MSWT) is designed to free the model from conventional mechanical supports. Under precise model design, a roll motion with appropriate control can be implemented in MSWT. This paper presents a modification of NCKU 10 cm/spl times/10 cm MSWT to accomplish the roll motion control in wind tunnel tests. The modification of this experiment includes position and attitude sensing and test model design. The position and attitude sensing is improved and set-up by a laser-optical circuit, quadrant detectors and dual-lateral detector in x-axis to ensure accurate measure. The rolling inertia is generated from a rotating mass inside the test model. With very careful design, a rocket model is fabricated for experiments. A passive PID control is implemented to achieve the predictable constant roll motion on the test model. A current feedback loop is applied to strengthen the control stability. Being different from other MSWT applications, the test model is locked by the position and attitude sensing via feedback control loop. Due to the accomplishment of motion test roll only constant speed in good control limitations, demonstrates performance. The idea of this study is to extend dynamic test capability in the magnetic suspension wind tunnel, and bring further valuable applications.


ABSTRACT Cretaceous deltaic sandstones of the National Petroleum Reserve in Alaska exhibit an extreme variability in their mineral makeup. A series of numerical techniques, however, provides some order to the petrographic characteristics of these complex rocks. Ten mineral constituents occur in the sandstones, including quartz, chert, feldspar, mica, and organic matter, plus rock fragments of volcanics, carbonates, shale, phyllite, and schist. A mixing coefficient quantifies the degree of heterogeneity in each sample. Hierarchical cluster analysis then groups sandstones on the basis of similarities among all ten mineral components--in the Alaskan example, six groupings characterized mainly by the different rock fragments. Multidimensional scaling shows how the clusters relate to one another and arranges them along compositional gradients--two trends in Alaska based on varying proportions of metamorphic/volcanic and shale/carbonate rock fragments. The resulting sandstone clusters and petrographic gradients can be mapped across the study area and compared with the stratigraphic section. This study confirms the presence of three different source areas that provided diverse sediment to the Cretaceous deltas as well as the general transport directions and distances. In addition, the sand composition is shown to have changed over time, probably related to erosional unroofing in the source areas. This combination of multivariate-analysis techniques proves to be a powerful tool, revealing subtle spatial and temporal relationships among the sandstones and allowing us to enhance provenance and paleogeographic conclusions made from compositional data.


The authors investigated the dynamics in spatial yields of primary production in the middle course of the Imo River in Etche, South-eastern Nigeria. At seven sampling locations along the course of the river, in situ measurements for water temperature, pH, turbidity, and dissolved oxygen (DO) were made with HORIBAU-10Water Quality Checker.Water samples were collected in 500 ml sterile containers for further laboratory analysis using standard methods. The light and dark bottle technique was employed in the measurement of primary production. Correlation coefficient (r) was used to establish relationships between physicochemical variables and primary production while the One-WayANOVAwas used to determine variance equality ofmeans in spatial yields.Means were further separated for the identification of variant productivity variables using the means plot. Wide variations were observed in turbidity (11.0-279.0, mean = 96.7 ± 9.3 NTU), DO (4.50-8.81,mean = 6.96 ± 0.14 mg/l), and sulphate (0.90-8.10, mean = 4.35 ± 0.25 mg/l) across the sampling locations. Gross and net primary production (GPP&NPP) aswell as community respiration (CR) ranged from0.01-1.12 (0.09 ± 0.02), 0.01-0.10 (0.04 ± 0.003), and 0.002-0.05 (0.02 ± 0.002) gCm-2d-1, respectively. Sampling location 1 showed the highest GPP, NPP, and CR of 0.09, 0.06, and 0.03 gCm-2d-1, respectivelywhile location 7 showed the least GPP of 0.06 gCm-2d-1, and locations 2-7 showed the least CRof 0.02 gCm-2d-1 each. At P<0.01, GPP correlated negatively with turbidity (r=-0.322) and sulphate (r=-0.297), NPP correlated positivelywith pH(r=0.404) and negativelywithDO( r=-0.567), turbidity (r=-0.592), nitrate (r=-0.435), phosphate (r=-0.365), and sulphate (r=-0.594) and CR correlated positively with pH (r=0.363) and negativelywithDO(r=-0.510), turbidity (r=-0.547), nitrate (r=- 0.405), phosphate (r=-0.304), and sulphate (r=-0.551).Variances inmeans of primary production variables showed inequality at P<0.05 at sampling locations 1 and 4. The observed oligotrophic production of the river was most probably due to low water nutrient levels, high turbidity and high relative humidity prevalent in the area.


Circadian clocks are required to coordinate metabolism and physiology with daily changes in the environment. Such clocks have several distinctive features, including a free-running rhythm of approximately 24 h and the ability to entrain to both light or temperature cycles (zeitgebers). We have previously characterized the EARLY FLOWERING4 (ELF4) locus of Arabidopsis (Arabidopsis thaliana) as being important for robust rhythms. Here, it is shown that ELF4 is necessary for at least two core clock functions: entrainment to an environmental cycle and rhythm sustainability under constant conditions. We show that elf4 demonstrates clock input defects in light responsiveness and in circadian gating. Rhythmicity in elf4 could be driven by an environmental cycle, but an increased sensitivity to light means the circadian system of elf4 plants does not entrain normally. Expression of putative core clock genes and outputs were characterized in various ELF4 backgrounds to establish the molecular network of action. ELF4 was found to be intimately associated with the CIRCADIAN CLOCK-ASSOCIATED1 (CCA1)/LONG ELONGATED HYPOCOTYL (LHY)-TIMING OF CAB EXPRESSION1 (TOC1) feedback loop because, under free run, ELF4 is required to regulate the expression of CCA1 and TOC1 and, further, elf4 is locked in the evening phase of this feedback loop. ELF4, therefore, can be considered a component of the central CCA1/LHY-TOC1 feedback loop in the plant circadian clock.


The effect of reheating to the semisolid state (soaking treatment) on the microstructure evolution of the A356 aluminum alloy prepared by ultrasonic melt treatment was studied in this paper. The results showed that in general the longer the soaking process the larger and the more round the grains obtained. Higher roundness occurs at shorter soaking times in the fine-grained ascast samples, and at longer times in the inhomogeneous or the coarser-grained as-cast structures. The optimum thixotropic condition (high roundness, 0.72, and small globule sizes < 90 μm) are achieved after 5 min. soaking in the samples treated by UST at 623 and 620oC, which is the typical soaking time dictated by the industrial practice in SSM. The amount of entrapped eutectic as observed after soaking treatments is uniquely very small, suggesting that the UST-treated ingots will have better formability in the semisolid state. The growth rate constants are substantially low: in the order of 479-748 μm3/s. These growth rate constants are much lower than those reported for MHDcast A356 ingots. The growth rates of the samples produced by UST in the liquid state (i.e., 626, 623 and 620oC. Note that liquidus temperature is 619oC) are lower than those of the samples treated in the semi-solid temperatures, i.e., 617 and 614oC. The Ostwald ripening is most likely the dominant growth mechanism in the UST-treated samples during the soaking treatments. These results reveal the feasibility and competence of UST as a potential route for thixotropic feedstock production.


Key words: vulnerability; resilience; livelihood; drought; Great Limpopo Transfrontier Conservation Area; south eastern Zimbabwe. Vulnerability and resilience have emerged as powerful analytical concepts in the study of socio-ecological systems. In this research these concepts are used to enhance our understanding of heterogeneous rural livelihoods in a semi-arid area on the western border of protected wildlife areas in Zimbabwe's southeast lowveld. The purpose of this thesis is to develop a methodological approach that helps understanding the vulnerability of rural livelihoods to change and relate this to adaptive mechanisms employed by people to cope with the resulting change. Although most households in the study area keep livestock, practice arable farming, and receive remittances, they differ in terms of their dependency on cattle, cropping, and non-farm and off-farm activities, especially in years of drought. Households most dependent on livestock – the cattle-based livelihood type – generally cope with hazards by selling cattle. Households of the crop-based livelihood type strive to spread the risk of crop failure by cropping across the landscape, ranging from flood plains to uplands on the interfluves. Households of the non-farm livelihood type rely for their survival on paid employment outside the study area, mostly of households' members working in South Africa. Fuzzy Cognitive Mapping (FCM) was used to assess the vulnerability of the three livelihood types to different hazards. The vulnerability analysis shows that policies relating to the permeability and/or enforcement of protected area boundaries can strongly aggravate the effects of other external influences, such as drought or climate change. To cope with drought-induced fodder shortages, people of cattle-based households have recently started to use Neorautanenia amboensis (Schinz). This tuber shrub, locally known as Zhombwe, is now saving many cattle from death in periods of drought, thus reducing livestock keeping households vulnerability to drought. This thesis shows the anthelmintic properties of Zhombwe; its distribution in the field was quantified. Crop experiments explored adaptive strategies which can be used by the households of the crop-based livelihood type to increase food self-sufficiency. Results show that by making better use of different landscape units in the area food production can be increased, both in good and bad rainfall years. By applying a method like FCM and by analysing quantitatively different options for increasing the resilience of the local households, this thesis shows that it is key to take into account the heterogeneity of rural households in an area, as adaption options differ strongly between them.


Horner syndrome is a constellation of neurological findings consisting of ipsilateral ptosis, miosis and anhidrosis. Partial Horner syndrome, comprising ipsilateral ptosis and miosis in the absence of anhidrosis, is a well-documented but uncommon manifestation of internal carotid artery dissection. Internal carotid artery dissection (ICAD) is a rare entity that either results from traumatic injury or can be spontaneously preceded or not by aminor trauma such as sporting activities, is a common cause of ischaemic stroke in young patients. As many as 40 to 50% of patients with carotid dissection will develop an ipsilateral Horner's sindrome.


Mesquite or Vilayati babul (Prosopis juliflora) is a drought resistant, evergreen, spiny tree with drooping branches and a deep laterally spreading root system. It grows in semi-arid and arid tracts of tropical and sub-tropical regions of the world and is spreading because the leaves are unpalatable and animals do not digest its seed. The mesquite has become a major nuisance; cutting or pruning its branches to form a canopy would provide shade for travelers, aid harvesting of pods, as well as make available wood for fuel. An average plant starts fruiting by 3-4 years of age and yields annually 10-50 kg pods/ tree, which can be collected from May-June and September-October. Availability of pods worldwide is estimated to be about 2-4 million metric tonnes. Ripe pods are highly palatable; on dry matter basis they contain 12% crude protein, 15% free sugar, a moderate level of digestible crude protein (7% DCP) with a high level of energy (75% TDN). The pods contain low tannin levels below those toxic to animals. Seeds contain 31-37% protein; pods should be finely ground before feeding to facilitate utilization of the seeds. Mesquite pods could replace costlier feed ingredients such as grain and bran contributing 10-50% of the diet. Phosphorus supplements need to be added when mesquite pod, exceeds 20% of animals' diet.


A comparison of pore fluids and authigenic carbonates sampled by the Ocean Drilling Program from the Nankai, Peru, Barbados, and Cascadia accretionary wedges illustrates significant disequilibria in oxygen isotopes, which in some cases may be related to rapid incursions of fluids along fault conduits in the past. The Peru, Barbados, and Cascadia carbonates have lower than expected δ 18 O PDB (Peedee belemnite) values for the measured downhole temperatures and isotope compositions of the pore fluids. In the Peru wedge the lower values may have resulted from past incursion of meteoric water, but in the Barbados and Cascadia wedges, the low δ 18 O PDB values were caused in part by past incursion of fluids with higher temperatures, probably along fault conduits. The temperature of fluids in the Cascadia wedge may have exceeded 100 °C, which is 90 °C higher than measured current downhole temperatures. The required high fluid-flow rates suggest a mechanism of seismically induced fluid migration to bring fluids rapidly from depths of greater than 2 km to the surface.


Currently, there is a lack of computational grammar resources for many under-resourced languages which limits the ability to develop Natural Language Processing (NLP) tools and applications such as Multilingual Document Authoring, Computer-Assisted Language Learning (CALL) and Low-Coverage Machine Translation (MT) for these languages. In this paper, we present our attempt to formalise the grammar of two such languages: Runyankore and Rukiga. For this formalisation we use the Grammatical Framework (GF) and its Resource Grammar Library (GF-RGL).


Dive computers have an important potential for citizen science projects where recreational SCUBA divers can upload the depth temperature profile and the geolocation of the dive to a central database which may provide useful information about the subsurface temperature of the oceans. However, their accuracy may not be adequate and needs to be evaluated. The aim of this study is to assess the accuracy and precision of dive computers and provide guidelines in order to enable their contribution to citizen science projects. Twenty-two dive computers were evaluated during real ocean dives for consistency and scatter in the first phase. In the second phase, the dive computers were immersed in sufficient depth to initiate the dive record inside a precisely controlled sea aquarium while using a calibrated device as a reference. Results indicate that the dive computers do not have the accuracy required for monitoring temperature changes in the oceans, however, they can be used to detect thermoclines if the users follow a specific protocol with specific dive computers. This study enabled the authors to define this protocol based on the results of immersion in two different sea aquarium tanks set to two different temperatures in order to simulate the conditions of a thermocline.


Abstract. Representative examples from 3 years of measurements from JPL's ground-based multiangle spectropolarimetric imager (GroundMSPI) are compared to a Mueller matrix bidirectional reflectance distribution function (mmBRDF). This mmBRDF is used to model polarized light scattering from solar illuminated surfaces. The camera uses a photoelastic-modulator-based polarimetric imaging technique to measure linear Stokes parameters in three wavebands (470, 660, and 865 nm) with a ±0.005 uncertainty in degree of linear polarization. GroundMSPI measurements are made over a range of scattering angles determined from a fixed viewing geometry and varying sun positions over time. This microfacet mmBRDF model predicts an angle of the linear polarization that is consistently perpendicular to the scattering plane and therefore is only appropriate for rough surface types. The model is comprised of a volumetric reflection term plus a specular reflection term of Fresnel-reflecting microfacets. The following modifications to this mmBRDF model are evaluated: an apodizing shadowing function, a Bréon or Gaussian microfacet scattering density function, and treating the surface orientation as an additional model parameter in the specular reflection term. The root-mean-square error (RMSE) between the GroundMSPI measurements and these various forms of the microfacet mmBRDF model is reported. Four example scenes for which a shadowed-Bréon microfacet mmBRDF model yields realistic estimates of surface orientation, and the lowest RMSE among other model options are shown.


The presence of networks of correlation between gray matter volumes of brain regions - as measured across subjects in a group of individuals - has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain connectivity modalities like functional and diffusion-weighted imaging, this approach can provide valuable insight into the mutual influence of regional trophic and plastic processes occurring between brain regions.
Previous investigations highlighted coordinated growth of these regions within specific structural networks in healthy populations and described their derangement in pathological states. However, a number of fundamental questions about the origin and significance of these couplings remains open and the mechanisms behind the formation of scMRI networks are still poorly understood. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, I coupled high resolution morpho-anatomical MRI with network-based approaches on a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J). To this purpose, I first developed a semi-automated pipeline enabling reliable Voxel Based Morphometry (VBM) of gray matter volumes in the mouse. To validate this approach and its ability to detect plastic changes in brain structures, I applied it to a cohort of aged mice treated with omega-3 polyunsaturated fatty acids (n3-PUFA). This study revealed that treatment with n3PUFA, but not isocaloric olive oil preserved gray matter volume of the hippocampus and frontal cortices, an effect coincident with amelioration of hippocampal-based spatial memory functions. I next employed VBM to investigate scMRI networks in inbred mice using a seed-based approach. In striking resemblance with human findings, I observed the presence of homotopic (i.e. bilateral) architecture in several scMRI cortical and subcortical networks, a finding corroborated by Independent Component Analyses. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. This work documents for the first time the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, and is poised to pave the way to translational use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states.


OBJECTIVE
The progress in workforce planning in preventive youth health care (YHC) is hampered by a lack of data on the current workforce. This study aimed to enumerate the Dutch YHC workforce. To understand regional variations in workforce capacity we compared these with the workforce capacity and the number of children and indicators of YHC need per region.

METHODS
A national survey was conducted using online questionnaires based on WHO essential public health operations among all YHC workers. Respondents (n=3220) were recruited through organisations involved in YHC (participation: 88%).

RESULTS
The YHC workforce is multi-disciplinary, 62% had > 10 years working experience within YHC and only small regional variations in composition existed. The number of children per YHC professional varied between regions (range: 688-1007). All essential public health operations were provided. Regional differences in the number of children per YHC professional were unrelated to the indicators of YHC need.

CONCLUSION
The essential public health operations provided by the YHC workforce and the regional variations in children per YHC professional were not in line with indicators of YHC needs, indicating room for improvement of YHC workforce planning. The methodology applied in this study is probably relevant for use in other countries.


Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron–glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses. Astrocyte intrinsic properties were found to be strongly analogous to those of vertebrate astrocytes, including a passive current-voltage relationship, low membrane resistance, high capacitance, and dye-coupling to local astrocytes. Responses to optogenetic stimulation of glutamatergic premotor neurons were correlated directly with anatomy using serial electron microscopy reconstructions of homologous identified neurons and surrounding astrocytic processes. Robust bidirectional communication was present: neuronal activation triggered astrocytic glutamate transport via excitatory amino acid transporter 1 (Eaat1), and blocking Eaat1 extended glutamatergic interneuron-evoked inhibitory postsynaptic currents in motor neurons. The neuronal synapses were always located within 1 μm of an astrocytic process, but none were ensheathed by those processes. Thus, fly astrocytes can modulate fast synaptic transmission via neurotransmitter transport within these anatomical parameters. J. Comp. Neurol. 524:1979–1998, 2016. © 2016 Wiley Periodicals, Inc.


Began as a compositional analysis of the oil-on-canvas portraits painted by John Singer Sargent, this thesis uses a selection of those images to relate national identity, cultural and social history within cosmopolitan British and American high society between 1890 and 1910. Close readings of a small selection of Sargent's portraits are used in order to undertake an in-depth analysis on the particular figural details and decorative elements found within these images, and how they can relate to nation-specific ideologies and issues present at the turn of the century.

Thorough research was undertaken to understand the prevailing social types and concerns of the period, and biographical data of individual sitters was gathered to draw larger inferences about the prevailing ideologies present in America and Britain during this tumultuous era. Issues present within class and family structures, the institution of marriage, the performance of female identity, and the formulation of masculinity serve as the topics for each of the four chapters. These subjects are interrogated and placed in dialogue with Sargent's visual representations of his sitters' identities. Popular images of the era, both contemporary and historic paintings, as well as photographic prints are incorporated within this analysis to fit Sargent's portraits into a larger art historical context.

The Appendices include tables and charts to substantiate claims made in the text about trends and anomalies found within Sargent's portrait compositions. This close statistical reading of Sargent's portrait oeuvre, while at times a subjective exercise, had not before been undertaken on this scale in art historical literature. The resulting data has been compiled to see if there is a correlation between compositional elements and nationality of sitter.


If one out of six of our medical-school graduates were unable to pass his state board examination, there would be great alarm. The fact that almost this many young physicians, having completed acceptable training in internal medicine, are unable, even after several attempts, to pass the examination by the American Board of Internal Medicine should be cause for concern. This fact in itself may have several possible explanations, but I bring it up as only one of the reasons why we should take a fresh, new look at training in internal medicine. In the changing scene of medicine I believe that it is high time we review our methods and goals. With the decline in general practice in the classic and broad sense, there has been a reciprocal rise in specialism in the United States (Fig 1). To me the most impressive fact is the rapid increase in the number


The scholarly literature on the eviction legal system has repeatedly concluded that eviction courts are courts of mass settlement. Landlords' attorneys pressure unrepresented tenants into signing settlement agreements in the court hallways in a factory-like process, and judges approve the agreements with a perfunctory rubber stamp. Yet while we know most eviction cases settle, no one has asked, much less answered, the salient follow-up question: what are the terms of these settlements? Based on the results of a rigorous study of a representative sample of eviction cases, this Article answers that question, and in doing so, generates a novel theory about the eviction legal system. The Article demonstrates empirically that the substantial majority of eviction settlements in the study jurisdiction contain a distinct set of interlocking terms that amount to what the Article labels "civil probation." Civil probation is the civil analog in the eviction context to probation in the criminal context. Specifically, it is the imposition of court-ordered conditions on a person's tenancy that, if violated, can result in swift eviction with few procedural safeguards. This Article is the first to conceptualize the phenomenon of civil probation and identify its existence in the eviction legal system. Through detailed data analysis, the Article empirically documents the prevalence of civil probation and describes its key features in the study jurisdiction. The Article then advocates for a new understanding of the eviction legal system as a whole through analysis of civil probation's consequences. First, a shadow legal system exists that operates alongside the statutory system that formally governs eviction proceedings. This shadow system undermines the rule of law and threatens public regulatory enforcement. Second, an ideology of control underlies the eviction legal system. Landlords, through the imposition of civil probation, use eviction filings not simply to recover possession or to collect rent, but rather as mechanisms to more tightly control, monitor, and regulate their tenants' conduct. And third, a phenomenon of "net-widening" of the eviction legal system is likely occurring, akin to the phenomenon that scholars have documented in the context of criminal probation. Civil probation motivates landlords to initiate eviction filings they would not initiate otherwise, and in doing so expands the reach and scope of the eviction legal system. The Article offers specific recommendations for reform based on these conclusions.


Abstract:  Towards the end of his life, Karl Barth had occasion to review his and Christian theology's relation to the work of Soren Kierkegaard. Barth's 'settling of accounts' with Kierkegaard issued in three searching criticisms: first, that Kierkegaard's work succumbs to a dour legalism, second, that it promotes a pious individualism at the expense of the church as a community with social and political responsibility, and third, that it promotes a new fixation upon subjectivity, enthralled by the idea of the possibility of a self-founding and groundless gesture of faith. This article explores the extent to which these are in fact warranted criticisms of Kierkegaard's theology. After considering how and by whom Kierkegaard was mediated to Barth, each of the three criticisms is taken up in turn and tested against a reading of texts from Kierkegaard's 'second authorship'. While it appears that in significant respects Kierkegaard's theology is different to what Barth takes it to be, what does become plain is that Kierkegaard's account of the church is in fact almost as phantasmal as the image of the Danish thinker at which Barth himself tilts for the most part.


ABSTRACT Root morphology will affect interplant competition for soil nutrients. Research was conducted to assess fine root fraction, mean root radius, specific root length, root length density, and nitrogen (N) uptake per unit fine root biomass of corn and velvetleaf over time and in response to nitrogen supply. Pots containing either corn or velvetleaf were embedded in the ground and received one of three N treatments. Plants were destructively sampled on 10 dates during each of two years and root subsamples analyzed using root scanning software. While corn root morphology was more responsive to N supply than velvetleaf, velvetleaf N uptake per unit fine root length was greater than that of corn at similar biomass. Results suggest that, in lieu of modifying root morphology to increase uptake efficiency when N is deficient, velvetleaf may invest more root biomass to produce a deeper tap root to reach nutrients deeper in the profile.


It appears that the concerted efforts of the watchmaking industry are leading towards a limit in mechanical watch accuracy. The general consensus in horology is that the time base's quality factor, a dimensionless number that characterizes the oscillator damping, needs to be improved in order to significantly increase timekeeper accuracy. The three classical mechanical time bases all suffer from limitations for mechanical watch applications. The pendulum used in precision mechanical clocks reaches quality factors of order 100000 but is too sensitive to the orientation of gravity to be used in portable timekeepers (watches). The balance and hairspring oscillator used in classical mechanical watches sees its quality factor limited to about 300 (450 in partial vacuum) by the friction in its bearings. The tuning fork used in electronic watches can reach quality factors of order 100000 but its high frequency and very small oscillation amplitude makes it very challenging to sustain mechanically. The solution appears to be flexure-pivot oscillators in silicon. Flexure-pivot oscillators use the elastic deformation of thin beams to guide the rotational motion of an inertial body and to exert a force opposed to its displacement, thus providing all the elements for a one degree-of-freedom mechanical oscillator. The use of flexures instead of bearings eliminates contact friction and monocrystalline silicon minimizes internal friction, leading to significant improvements in quality factor in comparison to balance and hairspring oscillators. Moreover, the rotational amplitude is compatible with existing sustaining mechanisms (escapements). Accurate timekeeping requires the period of oscillation of the time base to stay as regular as possible regardless of changes in operating conditions such as amplitude of oscillation, orientation with respect to gravity, temperature and shocks. This thesis focuses on minimizing the effects of amplitude and gravity that arise from the use of flexures. First, the nonlinear elastic behavior of flexures introduces a dependence of oscillation period on amplitude called isochronism defect. Second, the weight-bearing function of the flexures and their deviation from the motion of ideal linkages result in a contribution of gravity to their effective stiffness and hence an effect on their period. It is assumed that the other effects, i.e., temperature and shocks, can be solved with existing techniques. The first technical contribution of this thesis is to note that the isochronism defect is a second order phenomenon, and to deal with it by modifying the second order behavior of flexure spring stiffness or inertia. The second technical contribution is a design method to reduce the effect of gravity for all orientations of the time base to within the specifications of current mechanical watches, this by ingeniously placing the flexures and exploiting the position of the center of mass. These findings are embodied in three new flexure pivot architectures called Gravity Insensitive


Three heterotrophic bacterial strains were isolated from different locations in Puget Sound, Washington, by using biphenyl as the principal carbon source. These strains grow by using a limited number of organic compounds, including the aromatic hydrocarbons naphthalene, phenanthrene, anthracene, and toluene, as sole carbon sources. These aerobic, gram-negative rods are motile by means of single polar flagella. Their 16S rRNA sequences indicate that they are all members of the gamma subdivision of the Proteobacteria. Their closet known relatives are the genera Methylobacter and Methylomonas (genera of methane-oxidizing bacteria), uncultured sulfur-oxidizing symbionts found in marine invertebrates, and clone FL5 containing 16S ribosomal DNA amplified from an environmental source. However, the Puget Sound bacteria do not use methane or methanol as a carbon source and do not oxidize reduced sulfur compounds. Furthermore, a 16S rRNA base similarity comparison revealed that these bacteria are sufficiently different from other bacteria to justify establishment of a new genus. On the basis of the information summarized above, we describe a new genus and species, Cycloclasticus pugetti, for these bacteria; strain PS-1 is the type strain of C. pugetti.


Changing support, rejection or indifference to religion has shaped the relationship between government and religion in the United States, Australia and South Africa. The place of religion as moulder of national values in education has been determined by judicial interpretation in the United States, by legislature in Australia and by legislation, administration and constitutional interpretation in South Africa. These countries have faced the challenges of whether and how to permit the propagation of religious values into public education. Having a more accommodationist interpretation, Australia has well nigh furthered Christian values at public schools, which would not be allowed under the United States Constitution. South Africa has evolved its own legislative, judicial and administrative approach to addressing religion at schools from a perspective of impartiality, while aspiring to urge learners to achieve higher levels of moral judgment. The three approaches imply fundamental constitutional, political and judicial differences that allow little commonality. The varied legal mechanisms used by the three countries namely reflect differing historical and legal developments.


This experiment was designed to test the hypothesis that orally administered D‐glucaro‐1,4‐lactone might be excreted in the bile and thus suppress the activity of biliary β‐glucuronidase, which is believed to play a key role in the development of pigment gallstones. D‐Glucaro‐1,4‐lactone, 50 to 2,600 μmoles, was fed to adult Sprague‐Dawley rats which had a bile fistula and were kept in metabolic cages for bile and urine collection. A total of 21 feeding experiments were carried out. Quantitation of D‐glucaro‐1,4‐lactone and total D‐glucaric acid as the sum of D‐glucaric acid and its lactones in the bile and urine involved extraction of bile with tetrahexylammonium chloride, adjustment of pH, boiling and determination of percentage inhibition of β‐glucuronidase activity. The maximal velocity of β‐glucuronidase in the bile was also determined by the enzyme kinetic method. The results showed that 11% of administered D‐glucaro‐1,4‐lactone was excreted in the urine and only 0.2% in the bile, with D‐glucaro‐1,4‐lactone accounting for 20% of the total excreted D‐glucaric acid. The concentration and excretory rate of total D‐glucaric acid and D‐glucaro‐1,4‐lactone in the urine, but not in the bile, were proportional to the amount of D‐glucaro‐1,4‐lactone fed. The mean concentration of D‐glucaro‐1,4‐lactone in the bile after feeding was 0.06 mM, which was capable of suppression of 75% of β‐glucuronidase activity. Oral administration of D‐glucaro‐1,4‐lactone decreased biliary β‐glucuronidase concentration, slowed bile flow rate and hence decreased biliary β‐glucuronidase secretion. The effect reached a maximum of 80% suppression at an oral dose of 1,000 μmoles or more of D‐glucaro‐1,4‐lactone. The combined effect of the presence of D‐glucaro‐1,4‐lactone in the bile and the suppression of β‐glucuronidase secretion was the reduction of the endogenous β‐glucuronidase to 5% of its original activity. We therefore concluded that oral administration of D‐glucaro‐1,4‐lactone markedly lowers biliary endogenous β‐glucuronidase activity due to both the presence of D‐glucaro‐1,4‐lactone in the bile and the decrease in hepatic β‐glucuronidase secretion.


This dissertation concerns the rural retail trade (lanthandel) in the Revsund area 1870-1890. The area was industrialised from the 1850s by the inland expansion of the forestry and timber industries. The Free Trade Acts in 1864 paved the way for retailers outside the towns to play an important role in supplying the population with goods. The retail trade expanded over the whole period, but most importantly in 1871/75 and 1881/85. The growth was influenced by regional economic trends and the coming of the railway. During the 1880s there was a concentration of the retail trade as the numbers of retailers fell, while their averageincome grew. The evidence also suggests an increase in the division of labour among theretailers, as a few larger enterprises became suppliers to minor local retailers. Location, size and company type seem to have caused differences between three investigated retailers regarding their suppliers, their assortment of goods, and the social composition and overall behaviour of customers. General traits were that much demanded and bulky goods (groceries and iron ware) came from suppliers in Norrland, while other goods (textiles, clothes, household goods) came from other parts of Sweden. All three outlets were general stores. Freeholding farmers were the most important customers. The average volume of purchases was small and purchases were made infrequently. The larger retailers, a limited company and a partnership, took supplies from a wider area than the smaller retailer, a private enterprise, and the larger retailers had a wider and deeper product mix. Location mattered in that the retailer located in a parish centre where there were few competitors had more customers from social groups other than freeholders, as well as covering a wider geographical region, than the other two retailers, both located in a sparsely populated area. Being a consumer co-operative possibly explains why one retailer had a relatively large number of tenant farmers as customers. It is argued that the structure and organisation of the rural retail trade for the Revsundarea is applicable to the whole region of southern Norrland.


This article proposes and examines gender and life-stage factors as determinants of public worry and risk avoidance in a nuclear fallout scenario. Drawing on a survey (N 2,291) conducted in Sweden, the article demonstrates statistically significant results that women as well as parents with children at home are more likely to express high levels of worry for radiation exposure and have a preference to move away from a fallout area despite assurance of successful remediation. Moreover, a negative relationship is shown between age and both worry for radiation exposure and preference to move. These novel results from Northern Europe thus support a life-stage framing of public risk attitudes. As radiation physicists develop new methods showing that women and children are at higher risk of cancer than other groups at the same radiation exposure, we may actually see the precaution among women and parents as a regulating mechanism for the higher objective risk they face. The results are moreover in agreement with studies of public risk reactions in Japan, creating a strong knowledge base that human-induced radiation pollution is largely an intolerable risk to the public. Considering the public opinion, managing an intolerable risk through risk mitigation by remediation alone is likely insufficient in many cases. A viable strategy would offer a range of social support options that enable individual decision-making and the protection of risk groups.


We argue that partisan polarization in public support of the Affordable Care Act (ACA) is affected not only by policy design but also by which party makes those decisions. Using an innovative dataset that measures state-level quarterly ACA support from 2009 through the start of the 2016 presidential election, we find that opinions toward the ACA are less polarized in states with misaligned partisan environments where Republican governors support Medicaid expansion. We also find evidence that Republican opposition intensifies when a Democratic governor supports expansion. We do not find consistent evidence of such patterns for governors' positions on state health insurance exchanges. Our research sheds light on a key aspect of how health policy preferences respond to shifting political contexts in a polarized, federated polity.


Knowledge and behavior patterns are connected, and the results of learning can be measured through behavior. This study compares the behavior patterns of college students in the field of business in Ljubljana and Pula. Although no significant differences were expected, the study showed that Ljubljana students have a characteristic cognitive orientation and prefer using ideas rather than written rules in their work. Their decision-making is oriented toward long-term efficiency and long-term effectiveness, rather than short-term efficiency and short-term effectiveness, and their communication is indecisive and unreliable. Their behavior pattern is somewhat unstable, changing over time. In contrast, the Pula students' cognitive patterns are oriented toward ideas that they shape themselves. Their behavior inclines toward rules and their conscientious application, and their work is oriented toward short-term efficiency and long-term effectiveness, rather than short-term effectiveness and long-term efficiency. Their communication is reliable and they check statements in advance. The average behavior pattern of Pula students is very stable, with no particular variations between the sexes or years. The differences may be due to social circumstances, education styles, and perhaps tradition. Received: 23. 06. 2006. Accepted: 4. 11. 2006. Original scientific paper UDC: 65.012.4 (497.4) (497.5) 1. PROBLEM 1.1. Knowledge and its influence on behavior Knowledge is something that has always interested people. Everyone would like to know everything, and everyone has felt and feels the need to know something. When organizations ask themselves what kind of people they need, they always think about the knowledge of future employees. Knowledge has attained such breadth that in everyday conversation it even replaces other human qualities. One can, therefore, easily find requirements such as "knows how to solve problems creatively" and so on. Knowledge does not deserve such emphasis and such generalized importance. The idea behind the term "knowledge" often hides the expectation that people will react and behave in appropriate manners. Knowledge is not enough to yield an appropriate reaction or behavior. People must know how, be able, and want to react appropriately in a situation at work. This means that we must not only know, but also be capable and motivated at the same time. Together with other qualities, knowledge therefore acquires its final value and "worth" only when it is used appropriately at work. Knowledge is of no advantage to us if we cannot or do not use it. In this case, knowledge is more a warehouse of assorted (sometimes even applicable) information that cannot be implemented. People with this kind of knowledge know a great deal and feel a need for their knowledge to be respected. Of course, they cannot receive this respect on the basis of their accomplishments and they feel the need for a bit of pride because this is the only way they can convince the people around them that they are worth something. This quality - that knowledge is implemented and shown only in the second phase, in a non-direct manner after one's education is complete - suggests the idea that learning for the sake of knowledge cannot be useful. However, learning for the sake of successful work is, in any case, more applicable for many organizations. It has been a very long time since the first schools appeared that sought to systematically teach people to do what they would later be doing in organizations. The establishment of academic programs was primarily based on the systematization of jobs, or job descriptions. Everything that was necessary for a particular job was called a profession and it was, therefore, possible to fashion a catalog of knowledge that the candidate could master in order to do the work of his profession. Some jobs remain relatively stable today, which means that the tasks are very strictly prescribed, and in this situation, it is not difficult to design a corresponding academic program. …


This chapter takes as its case study a Doctor of Education programme in the Centre for Excellence in Media Practice (CEMP) at Bournemouth University. It offers some background to the development of a particular blended learning model and considers the experience of the participants, assessing the degree to which the design of the virtual learning environment produced certain kinds of participation and resistance; I am interested in trying to explain the things which worked, and which didn't work in this particular instance of an educational VLE. The case study is presented as a narrative, without theorisation, but first I discuss critical approaches to technology-assisted learning. Ultimately, I argue, although it is important to attend to the design and structure of virtual learning environments, the frame for this must always be the social dimension of interaction, participation and learning.


relapse, one with secondary DLBCL 11 months later). ctDNA analyses for the remaining patients are in process and will be presented at the meeting. Conclusion: Concurrent pembrolizumab + AVD represents highly effective frontline therapy for CHL, but results in spurious PET find- ings in a significant proportion of patients despite most patients hav-ing undetectable ctDNA and no relapse. ctDNA may represent a more sensitive and specific response assessment tool to be studied in larger datasets. Background: Optimizing therapies for pts with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL) after anti–PD-1 therapy fail-ure remains of clinical interest. The multicohort phase 1/2 MK-4280– 003 study (NCT03598608) evaluated the safety and efficacy of a LAG-3 inhibitor, favezelimab (MK-4280), + pembrolizumab (pembro) in pts with R/R hematologic malignancies. Cohort 2 focused on pts with R/R cHL after anti–PD-1 therapy. Methods: Part 1 was the safety lead-in phase to determine the recom-mended phase 2 dose (RP2D), followed by a dose-expansion phase (part 2). Eligible pts in cohort 2 had cHL and relapsed after or were ineli-gible for autologous stem cell transplantation and PD after ≥2 doses of anti–PD-1 therapy. Pts in part 1 received escalating doses (per mTPI design) of pembro IV 200 mg Q3W and favezelimab IV 200 mg or 800 mg Q3W. In part 2, pts received pembro + favezelimab at RP2D for ≤35 cycles. Primary end point was safety. ORR was a secondary end point. DOR, PFS, and OS were exploratory end points. Database cutoff was March 21, 2022. Results: Part 1 identified 1 dose-limiting toxicity (DLT; autoimmune hepatitis [grade 4]) among the first 6 pts from all cohorts at the favezelimab 200 mg dose. No DLTs were found after an additional 15 pts at the 800 mg dose; RP2D was defined as 800 mg Q3W + pembro 200 mg Q3W. 34 pts were enrolled in cohort 2; median age was 37.5 y, 62% had ECOG PS 0, and 94% had ≥4 prior lines of therapy. At database cutoff, 22/34 pts had discontinued (11 PD; 7 AEs; with current bispecific antibodies, high complexity and cost with CAR T-cells or lack of efficacy with many simple monoclonal antibodies targeting tumor-associ- ated antigens. Thus, it is highly desirable to develop new technologies that can overcome these limitations. Here, we introduce our strategy to retarget various immune effector cells simultaneously with half-life extended bispecific scFv constructs to Hodgkin lymphoma-associated antigens e.g., CD30. In doing so, we target CD3, CD16 and CD28 on immune effector cells. Half-life extension is achieved by fusing the scFv constructs to a repetitive amino acid sequence without secondary structure and immunogenicity developed by us. After optimizing the production of our constructs in mammalian protein production systems we performed functional in vitro validation. Our data shows that the designed bispecific scFv constructs can bind their targets specifically and simultaneously and facilitate the formation of an artificial immunolog- ical synapse with immune cells secreting toxic proteins such as perforin and granzymes leading to the apoptosis of the lymphoma cells. We show direct cytotoxicity towards tumor cells in vitro and a target-cell specific release of cytokines such as TNF α and IFN γ by effector cells. We are now moving some constructs into cell line xenograft mouse models for further in vivo validation.


Hierarchically structured data collections often need to be visualized for the purposes of digital information management and presentation. File browsing, in particular, has an inherent hierarchical structure and plays an important role in the context of personal information management (PIM). A multitude of file browsers are nowadays available, offering different functionalities, while users adopt diverse practices and habits for browsing activities. In this paper, we investigate these aspects to obtain insights into their advantages and disadvantages and suggest solutions in the area of PIM, as well as in other domains employing similar visualization paradigms. The presented study focuses on the two most widespread visualizations used by file browsers, the indented list and zoomable interface paradigms, and assesses their effectiveness for various tasks and contexts, both by exploiting results on existing evaluations on hierarchy visualizations and folder hierarchy visualizations in particular, and by conducting an interview-based user study.