An attention filter is a neural process acting across space to modulate the effectiveness with which a target feature (e.g., blackness) is processed. I investigated the range of attention filters achievable for grayscale in estimating two summary statistics: (1) centroids and (2) mean orientation (MO) judgments. Chapter 1: in estimating centroids of dots varying in grayscale, participants can achieve two types of attention filters: 1) One gives equal weight and 2) one gives weight graded in proportion to contrast intensity. Comparison of results from different display types suggested three grayscale centroid filters accessible: (1) one assigns equal weight to all grayscales; (2) one assigns weight near 0 to negative contrasts, weight proportional to contrast intensity to positive contrasts; (3) and one assigns weight near 0 to positive Weber contrasts, weight proportional to contrast intensity to negative contrasts.Chapter 2 investigated whether vision can access the same grayscale-selective attention filters for estimating centroids as MO of bars. Each task had three attention conditions: Attend-Light (equal weight to positive contrasts, weight 0 to negative contrasts), Attend-Dark (equal weight to negative contrasts, weight 0 to positive contrasts), and Attend-All (equal weight to all). Centroid filters matched equal targets well; MO filter accuracy was somewhat worse. Efficiencies, or estimated proportion of items used by an ideal detector, were more than 100% higher for centroids than MO. The pattern of Efficiencies across tasks and attention conditions suggested different strategies between tasks: centroid results suggested participants were applying a filter to the input and computing the centroid of the output; MO results suggested participants were selecting a subsample of bars and basing responses on that sample. Chapter 3: attention filters giving weight inverse to dot contrast intensity can be achieved. This requires preattentive vision to dampen saliency of the extreme contrast and sharply tune to the low contrast. This implicates a preattentive mechanism sharply tuned to dim items, with discrimination dropping more rapidly with increasing contrast intensity. In the Attend -Dark/ -Bright conditions, filters gave high weight to target polarity's lowest contrast dots, but weight near 0 to the distractor polarity. This implicates separate mechanisms responsive either to only positive or negative contrasts.


The article examines the jurisprudential value of Tribunal decisions and awards from both theoretical and empirical perspectives. The article considers four factors for assessing the precedential value of awards and decisions of international tribunals: (i) the integrity and authoritative standing of the court or tribunal issuing the earlier decision; (ii) the similarity of the relevant facts in the two cases, (iii) the similarity of the law relied on as necessary to making the decision (the decisional law); and (iv) the merits or instructive value of the prior tribunal's reasoning in reaching its decision - hence, its exposition of the law. Applying these factors to the jurisprudence of the Iran-U.S. Claims Tribunal demonstrates the importance of that jurisprudence as persuasive authority in investor-State arbitration. Part I of the article examines the extent to which Tribunal precedent has been cited by parties and tribunals in investor-State arbitrations. The citation analysis finds significant citation of Tribunal precedent in awards and decisions in arbitrations administered by the International Centre for Investment Disputes (ICSID), and in party submissions in arbitrations under Chapter 11 of the North American Free Trade Agreement. Thus, the awards and decisions of the Iran-U.S. Claims Tribunal have been and likely will continue to be an important source of authority in investor-State arbitration.


Abstract
Purpose: This research aims to obtain a description of the policy of developing human resource educators at the University of Dili in accordance with applicable academic regulations.
Research methodology: The method used in this research was a descriptive qualitative method. Six respondents were determined as research samples. The research instruments for this study were interview guides, notebooks, recording devices, test books and researchers. Data collection was done through interview method and the data was analyzed by referring to Miles and Huberman's Intractive model framework.
Results: there are some efforts to develop the human resources of educators in universities such as sending of teaching staff to continue their education and various policies that enable the development of educators' human resources. Some factors that influence the development of human resource educators in universities are the organizational structure, organizational policies, allocation of funds, the level of educators' education and the participation of educators in support for the development of human resources
Limitations: this research only discusses the development of educators as human resources at the University of Dili and various factors that influence it.
Contribution: This research was conducted to answer problems related to the management of development for educators as  human resources at the University of Dili and what factors influence the development of teaching human resources at the University of Dili Timor-Leste
Keywords: Development, Human resource, Educator


FDDI is an optical standard for data transmission which gave a transmission speed of 100 Mbit/s in a local area network. The throughput and response time is a measure of performance of a network. The performance of the FDDI system depend on various parameters namely ring latency, TTRT, number of stations, bandwidth, transmission delay, propagation time and group velocity. The throughput or the efficiency of the network can be increased by controlling and then minimizing the ring latency with respect to TTRT. The response time can be improved by decreasing the transmission delay and propagation time with respect to the bandwidth and group velocity respectively.


Daniel Diez Couch, "Setting Fires with Hawthorne: 'Earth's Holocaust' and Book Burning in Nineteenth-Century America" (pp. 87–113)
 Nathaniel Hawthorne burned pages and pages of his own writing over the course of his life and investigated the topic in two tales, "The Devil in Manuscript" (1835) and "Earth's Holocaust" (1844). While the former borrows from his own life experiences, the latter presents a cataclysmic vision of the destruction of all literature. Yet Hawthorne does not offer a typical lament—based in liberal ideologies of the progress of knowledge and the sanctity of the written word—for the all-consuming holocaust. Rather, he argues that the pyre yields a transformative and unexpected effect on the aesthetic and temporal qualities of the texts. Drawing on contemporary accounts of book burnings, Hawthorne generates a productive vision of the act by which the fire transforms texts into a visible spectacle of beauty. "Earth's Holocaust" thus offers an aesthetic avenue for understanding literary bonfires. Moreover, Hawthorne rejects the premise that such events end the temporal lifecycle of texts. Throughout the tale, he contends that even though book burnings will occur time and again regardless of human reformation, books can surpass the effects of the flames even if such a process only occurs imaginatively. In the dematerialization of books—in turning them from a complete, bounded whole into embers and particles of dust—Hawthorne finds a redemptive energy.


The COVID-19 pandemic has spread globally for several months. Because its transmissibility and high pathogenicity seriously threaten people's lives, it is crucial to accurately and quickly detect COVID-19 infection. Many recent studies have shown that deep learning (DL) based solutions can help detect COVID-19 based on chest CT scans. However, most existing work focuses on 2D datasets, which may result in low quality models as the real CT scans are 3D images. Besides, the reported results span a broad spectrum on different datasets with a relatively unfair comparison. In this paper, we first use three state-of-the-art 3D models (ResNet3D101, DenseNet3D121, and MC3\_18) to establish the baseline performance on three publicly available chest CT scan datasets. Then we propose a differentiable neural architecture search (DNAS) framework to automatically search the 3D DL models for 3D chest CT scans classification and use the Gumbel Softmax technique to improve the search efficiency. We further exploit the Class Activation Mapping (CAM) technique on our models to provide the interpretability of the results. The experimental results show that our searched models (CovidNet3D) outperform the baseline human-designed models on three datasets with tens of times smaller model size and higher accuracy. Furthermore, the results also verify that CAM can be well applied in CovidNet3D for COVID-19 datasets to provide interpretability for medical diagnosis. Code: https://github.com/HKBU-HPML/CovidNet3D.


Control Objectives for Information and Related Technology (COBIT) becomes very popular in recent years and is regarded as the most comprehensive IT governance framework. However, its actual utilization and effectiveness are not clear due to the lack of academic studies. Also, the proliferation of other IT standards and best practices, such as ISO27000 series and ITIL, creates great challenges for organizations to understand their relations and to take advantage of them. The main objective of this research is to explore the practicability of COBIT framework and its actual usage. A pilot COBIT program within an IT department was carried out to collect primary data. The actual usage of COBIT tools is analyzed and compared to their theoretical design. Practical problems of COBIT framework are identified. A COBIT-BSC model is proposed to illustrate a simple way of structuring COBIT control objectives. This study will contribute some practical insights to COBIT framework and help organizations take advantage of COBIT as well as other IT control frameworks.


BACKGROUND
In penetrating thoracoabdominal trauma, it is necessary to evaluate both pericardial fluid and the diaphragm directly. Trans-diaphragmatic pericardial windows provide direct access to the pericardium and diaphragm, but expose the patient to the risks of laparotomy. We hypothesize that transabdominal laparoscopic pericardial windows are a safe and effective alternative to trans-diaphragmatic pericardial windows in stable patients.

METHODS
This is a retrospective observational study of stable patients with thoracoabdominal penetrating trauma at a Level I Trauma Center between January 2007 - June 2015, comparing outcomes after trans-diaphragmatic (TDW) versus laparoscopic pericardial windows (LPW).

RESULTS
A total of 99 patients with penetrating trauma had a diagnostic pericardial window, 33 of which were laparoscopic. Stab wounds were most common (80, 80.8%), compared to gunshot wounds (19, 19.2%). Of 11 patients with a positive pericardial window, 10 (90.9.%) were associated with a cardiac injury. There was no difference in the ratio of positive pericardial windows between patients who had TDW vs. LPW (8/66, 12.1% vs. 3/33, 9.1%, p=0.651). One patient had a complication related to a negative pericardial window in the laparoscopic group. There was no difference in complication rates between TDW and LPW (p=0.155). Mean length of stay (LOS) was longer in TDW compared to LPW (12 vs. 5 days, p=0.046). One patient died during index admission in the TDW group, but there was no difference in mortality rates between TDW and LPW during the index admission (p=0.477). Median length of follow-up was 29 days (range 0-2,709). On long-term follow-up, there was also no difference in mortality rates between TDW and LPW (2/66, 3.0% vs. 2/33, 6.1%, p=0.470).

CONCLUSION
In hemodynamically stable patients with thoracoabdominal injuries, LPW is a safe and effective technique for evaluating both pericardial fluid and the diaphragm. Laparoscopic pericardial window is a viable alternative to exploratory laparotomy and trans-diaphragmatic pericardial windows.

LEVEL OF EVIDENCE
Level III.


Prompted by the spirit of the new Truth and Reconciliation Commission, soon beginning its work in examining the legacy of the residential school system, this paper seeks to begin to reconcile the governance principles espoused by the Institute On Governance (following the UNDP) with Aboriginal governance traditions. After discussing fundamental elements of governance and good governance (I) it presents the Institute's five governance principles (II), then probes their origins of the principles in international human rights law, Western political theory and Western historical experience (III). The paper explores some possible First Nations governance principles (IV), suggesting that the two, though distinct, are converging and in fact might complement and correct each other (V). The paper concludes with some thoughts on the requirements of genuine reconciliation.


This is the author accepted manuscript. The final version is available from Liverpool University Press via the DOI in this record


Aspect level sentiment classification is a fine-grained sentiment analysis task. To detect the sentiment towards a particular aspect in a sentence, previous studies have developed various attention-based methods for generating aspect-specific sentence representations. However, the attention may inherently introduce noise and downgrade the performance. In this paper, we propose constrained attention networks (CAN), a simple yet effective solution, to regularize the attention for multi-aspect sentiment analysis, which alleviates the drawback of the attention mechanism. Specifically, we introduce orthogonal regularization on multiple aspects and sparse regularization on each single aspect. Experimental results on two public datasets demonstrate the effectiveness of our approach. We further extend our approach to multi-task settings and outperform the state-of-the-art methods.


Architecture can be seen as a discipline that poses several design challenges from conception to
design realization stages. This path by which the idea of an architect is translated from the mind to
paper and then birthed to life is known as design process. To solve design problems, architects have
to go through a systematic design process, which vary with individuals and groups. In whatever way,
this is done, the process determines the output and resulting performances. Hence, this study
investigates varying design processes and the impact it has on students' performances in their design
studio courses. This study adopted a survey approach with 300 structured questionnaires distributed
in three Schools of Architecture in southwest Nigeria. The Results showed two distinct design process
approach by students namely: (i) Students who derive design concept in mind and stick to it from the
beginning of the project to the end; and (ii). Students who embark on research with guided relevant
key parameters to direct their project. Findings show that students in the latter category perform better
in the design studio. Furthermore, the study recommended that the design process approach is
important, but the rule of thumb is not a major determinant factor to performance in architectural
design studio.


There are periods in the lives of men and institutions that are traditionally recognized as justifying some form of celebration or special attention. The fact that this is the 50th anniversary of the Council on Medical Education and Hospitals of the American Medical Association, as well as the 50th Annual Congress on Medical Education and Licensure, merits some reference to its history and accomplishments. A comprehensive and detailed history of the Council by Dr. Victor Johnson was included in the "History of the American Medical Association: 1847-1947" published in 1947 as a feature of the centennial celebration of the Association. In making references to certain aspects of this history, I have quoted freely from Dr. Johnson's history of the Council. That the primary objective in the establishment of the American Medical Association was the improvement of medical education is shown in the preamble of the resolution adopted by the New


Head and neck cancers remain difficult to treat due to their aggressive biological behavior and delicate functional anatomy from which they arise. This particularly applies for advanced and recurrent cases, when feasible treatment options are becoming limited due to expected poor patient survival and/or functional outcome. Salvage surgery is the treatment modality of choice in case of resectable locoregional recurrence. However, recurrent head and neck squamous cell carcinoma (HNSCC) is often detected in a late stage, rendering salvage surgery with curative intent impossible. Further, for a considerable number of patients undergoing salvage surgery with curative intent, outcomes remain poor due to a high risk of complications and morbidity. Although new treatment strategies such as adjuvant immunotherapy are being developed and existing diagnostics are improving, 5-year overall survival rates of HNSCC patients in The Netherlands have remained stable at 57%-58% over the past few decades. An absolute increase in incidence from 15% to 50% of prognostically favorable HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) cases has been observed in The Netherlands in the same period, even further indicating rather stagnant survival numbers of HPV-negative HNSCC cases. This emphasizes the need for early detection of recurrent disease in order to improve chances for a successful curative treatment plan instead of a palliative regimen. In the era of emerging precision medicine, a more personalized approach to HNSCC care is desired to pave the road for new, more accurate methods of early detection of recurrence, prognostic stratification, and therapeutic response prediction. Ideally, molecular biomarkers are being used that accurately represent tumor (epi)genetic status, and at the same time allow minimally invasive collection. Lastly, this has to be practically feasible for implementation into routine clinical practice. Therefore, the aim of this thesis was to identify potential liquid biopsy based diagnostic biomarkers, and investigate whether they are suitable for clinical implementation and use for the early detection of recurrent or residual HNSCC in order to improve the overall survival and quality of life of HNSCC patients in the future. In this respect, this thesis has contributed to the fast growing field of liquid biopsy in HNSCC patients by exploring a wide variety of (pre)clinical aspects, and thereby paved the road for further, more focused research on ctDNA analysis in HNSCC patients. Although several of these aspects remain unclear, this thesis provides a lead for further investigating the use of liquid biopsies for personalized head and neck cancer management in order to improve patient disease outcome and quality of life ultimately.


The introduction of 5G New Radio (NR) promises flexibility and adaptability to cater a wide variety of services. One of the key ingredients for achieving such requirements is the employment of multiple numerologies. This versatility brings along with it some complexity as well in terms of resource allocation using multiplexed non-orthogonal numerologies. Another key enabler is the concept of Shortened TTI/ Mini-slots for addressing low latency applications. In this paper, we propose a dynamic resource allocation scheme to reduce the average scheduling latencies in a network using multiple numerologies in conjunction with mini-slots. A system level simulation has been conducted to compare different nominated combinations of numerologies (with mini-slots) and service requests and it has been observed that with a minor compromise of minimum achievable scheduling latency for high priority requests, a significant reduction of average scheduling latency is attained considering all types of diverse service requests with different priorities.


Streets-in-the sky is a form of multi-storey working class housing
which is important in today's society for two reasons.
Firstly, because street-deck housing became especially popular during
the post-war rebuilding of British cities following the inter-war
introduction of the idea and the successful development of the Park Hill
scheme in Sheffield in the 1950s. In the 1960s, especially in the second
half of the decade, the design professions, several leading local authorities,
and central government undertook the development of street-deck housing
throughout the United Kingdom. It proved to be especially popular, outside
London, in the economically declining or static regions of England; relatively
little being built in Scotland, Wales or Northern Ireland. Hence streets-in-the-sky tended to be developed in those English regions where the basic
export industries of coal, iron and steel, shipbuilding and textiles were
subject to the most comprehensive state-controlled restructuring. The large scale public investment and labour resistance to change associated with
industrial restructuring were therefore often partnered by a form of high
density housing more acceptable to the financially overburdened local
authority and the 'anti-flats' culture of the English than the economically
and socially unpopular tower block.
Following the building programme there was a decline in the fortunes
of modern architecture, the labour movement and the United Kingdom economy.
With that decline came a pronounced reduction in the quantity and quality of
this type of urban housing. In the 1970s, the poor construction, difficult
access, anti-social use of the 'street' and the stigma attached to living
on the estates usually led to the schemes becoming especially difficult-to-let.
Thus, in a quarter of a century, this particular housing form had changed
from being a central element in the modern architectural urban utopia to its
opposite - a microcosm of the problems facing British cities in their decline.
Secondly street-deck housing is important because its history brings
to light the contradictions between different ideas and different political
and economic interests, and reveals how these contradictions can be
temporarily overcome by the development of a particular form of urban housing.
These patterns of conflict and consensus are not fully comprehended by
existing "counter-revolutionary" and "revolutionary" theories of urban form
and change. In the former case we have tried to show how the assumptions of
so called 'postmodernism' are incorrect. And in the latter, how a far broader
interpretation of the totality (base and superstructure) is necessary as a
basis to knowledge and action.


The fastest growing demographic sectors of Washington agriculture are Latino, Asian, and women farmers. The majority of these farms are small, with over three-fourths of Latino, Hmong, or women-operated farms having fewer than 50 acres and less than $50,000 in sales. Small farms make up 90 percent of all Washington farms, with 35,269 counted in the last census. Unfortunately, most conventional farming education models are not well-suited to farmers with limited access to land, water, and capital, or with limited literacy or limited English proficiency. Meeting the needs of this new generation of farmers will require rethinking many standard approaches to public agricultural research, education, and assistance. This article examines various alternative formats for reaching diverse producers with sustainable farming education that have been piloted by the Washington State University Small Farms Program, including participatory courses, farmer-to-farmer learning strategies, experiential workshops, audiovisual strategies, and simultaneous translation.


Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsisMethods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery.Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients.Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.Registration: This clinical trial was registered with www.clinicaltrials.gov under NCT00004494. Trial was registered before the first patient was enrolled.


The necessity to operate on hip dislocation has decreased because the natural history of this congenital disease has been completely changed by using clinical and ultrasonographic screening. At present in our country surgical reduction is indicated in the rare cases of true congenital severe hip dislocation or in the few cases missed during screening. Our long experience in the treatment of such pathology since the start of the 1960s is summarized in this paper in which we describe our indications in surgical treatment of dislocated and subluxated hips affected by DDH. We point out our approach to open the dislocated hip laterally explaining the advantage of this particular and not common approach. We also describe the radiological assessment necessary to evaluate residual dysplasia in order to plan the necessary pelvic or femoral osteotomy to correct these residual joint alterations.


In mid-2008, high employment and low unemployment rates characterised the Estonian labour market in comparison with the average of the EU15 countries. While aggregate outcomes improved during 2000-07, large inequalities persisted across regions, ethnic groups, and workers with different skill levels. As Estonia entered recession in 2008, the unemployment rate almost doubled between the 2nd and the 4th quarter, and is expected to rise further in 2009 and 2010. More flexible labour markets will be a key adjustment mechanism during the recession as well as in the medium term if Estonia is to become a knowledge-based economy. Given the currency board arrangement and low synchronisation with the euro area, flexibility is also needed to cushion asymmetric shocks. In December 2008, parliament adopted the new Employment Contract Act, deregulating employment protection while increasing income security of the unemployed. This paper discusses options for removing the remaining barriers that impede worker reallocation across jobs, sectors, and regions into more productive activities.


This study examined whether preterm infants are more vulnerable to the effects of prenatal drug exposure than are full-term infants. The sample of 235 low-income African American mothers and their infants included 119 cocaine-polydrug users, 19 alcohol-only users, and 97 nonusers; 148 infants were full term and 87 were preterm. Direct effects of exposure on birth weight, birth length, ponderal index, and irritability were moderated by length of gestation: Fetal growth deficits were more extreme in later-born infants, whereas increases in irritability were more extreme in earlier born infants. Effects of exposure on cardiorespiratory reactivity to a neonatal exam were not moderated by length of gestation. In general, effects of exposure occurred for both cocaine-polydrug and alcohol only users and so could not be unambiguously attributed to either of these drugs alone.


In the traditional methodology of CAD system teaching, one starts with acquirement of technical drawing principles and design of technical schemes and drawings based on manual drawing. Only consequently students learn to draw the schemes and technical drawings in some of the CAD systems. An alternative possibility to teach CAD/CAE systems could be to start immediately with machine element draughts and modelling and to the technical drawing teaching to pay attention only marginally, in a reduced time allocation. A key question related to this, by the authors proposed way of teaching CAD/CAE systems, is whether the reduction of the technical drawing teaching will not have a negative impact on the students` achievements. The answer to this question should be found out from a pedagogical experiment which the authors are going to carry out and a methodology of which is presented in the paper.


The variability in duration and severity of infection with Giardia lamblia is likely to be due to trophozoite interactions with immune and nonimmune components of the small intestinal milieu. Despite its potential importance, nothing is known of the isotype or the specificity of the secretory antibody response to G. lamblia. In the present study, we show that serum and secretory antibodies recognize many Giardia antigens whose expression is induced by exposure to selected intestinal conditions. Isotype-specific immunoblots of antigens from trophozoites grown at pH 7.0 without bile or at the intestinal pH of 7.8 with bile were reacted with milk or serum antibodies from subjects with or without histories of giardiasis. While the results were complex, several key observations emerged. Serum and secretory immunoglobulin A (IgA), IgM, and IgG antibodies reacted with many regulated antigens. Antigen recognition patterns varied with isotype and between milk and serum antibodies of the same isotype. Antigen recognition also differed among subjects. Antibodies from virtually every patient recognized some G. lamblia antigens. Furthermore, milk and/or serum samples from putative controls without histories of giardiasis were positive more frequently than would be predicted from published prevalence studies, suggesting either that these antibodies may be cross-reactive or that undiagnosed infections with G. lamblia may be more common than previously thought. Thus, recognition of neoantigens induced by host conditions may be due to conserved or cross-reactive epitopes which could constitute a form of immune evasion by G. lamblia.


In this study we aim at analyzing what the researchers in the area of School and Educational Psychology in Brazil think about the role of psychologists in Education, considering the movement of critical current in the area. For this purpose, we surveyed the academic production in the area of Educational and School Psychology published in books and collections in the period from 2000 to 2007. We found 36 works on the subject, six books and 30 collections in which we analyzed 131 chapters. Most publications refers to proposals for intervention in highlighting the importance of understand how to give the relations in which the school complaint is produced; in understanding the school as the principal agent of social integration; in articulating the family history with the school history; in including teachers in the intervention process; in finding the context in which they produce and express individual conflicts, among others. In general, these works present proposals for practicing psychologists in Basic Education in an ethical-political dimension.


1. Zebra mussels (Dreissena polymorpha) derive their energy from the pelagic energy pathway by filtering plankton. Because zebra mussels occur in high densities in littoral habitats, they potentially constitute an important trophic link between littoral consumers and pelagic energy sources. Northern map turtles (Graptemys geographica) are widespread in North America and consume zebra mussels. 2. We used stable isotopes analyses to quantify the flow of energy from the pelagic pathway to northern map turtles and to infer the contribution of zebra mussels to map turtle biomass. We then built a bioenergetic model to estimate the annual intake of zebra mussels by northern map turtles in Lake Opinicon, Ontario, Canada. 3. Stable isotopes analyses indicated that zebra mussels constitute between 0% and 14% of the diet of males and between 4% and 36% of the diet of females. Assuming that zebra mussels account for all of the pelagic contribution, we estimated that map turtles consume 3200 kg of zebra mussels annually. Because female map turtles are much larger than males and consume more zebra mussels, they are responsible for 95% of the zebra mussel biomass ingested annually. 4. The pelagic pathway supports an important part of the standing crop biomass of map turtles in Lake Opinicon. We highlight the importance of freshwater turtles in lake ecosystems. Unravelling the trophic interactions mediated by freshwater turtles will lead to a more integrated picture of lake ecosystems.


Type 2 diabetes patients have a higher risk of developing cardiovascular and cerebrovascular diseases, therefore statins are recommended for almost all diabetes patients. Although it has been shown that statins can have substantial health and economic benefits, treatment in clinical practice is often suboptimal. This is due to low-dosing, lack of intensification of treatment and non-adherence to treatment. Patients on a low dose are less likely to achieve treatment targets, which could be because they are more sensitive to non-response due to non-adherence. Non-adherence and discontinuation rates are high in clinical practice and associated with patients' preferences. In our study patients where however willing to continue lipid-lowering treatment, which might be because we gave specific information regarding benefits and drawbacks of stopping and continuing treatment. The willingness to continue and the importance patients attached to specific treatment characteristics (e.g. risk reductions in cardiovascular events and risk for adverse events) were dependent on characteristics like age, clinical history and education. Therefore interventions aimed at improving adherence should take patient characteristics into account. As treatment is suboptimal due to both patient related factors (non-adherence and patients' preferences), and physician related factors (treatment dosing and treatment modifications), interventions to optimize statin treatment should be multifaceted combinations that target both the patient and the physician.


Objective To assess, in a cross-sectional study, the feasibility and immediate efficacy of laser shoes, a new ambulatory visual cueing device with practical applicability for use in daily life, on freezing of gait (FOG) and gait measures in Parkinson disease (PD). Methods We tested 21 patients with PD and FOG, both "off" and "on" medication. In a controlled gait laboratory, we measured the number of FOG episodes and the percent time frozen occurring during a standardized walking protocol that included FOG provoking circumstances. Participants performed 10 trials with and 10 trials without cueing. FOG was assessed using offline video analysis by an independent rater. Gait measures were recorded in between FOG episodes with the use of accelerometry. Results Cueing using laser shoes was associated with a significant reduction in the number of FOG episodes, both "off" (45.9%) and "on" (37.7%) medication. Moreover, laser shoes significantly reduced the percent time frozen by 56.5% (95% confidence interval [CI] 32.5–85.8; p = 0.004) when "off" medication. The reduction while "on" medication was slightly smaller (51.4%, 95% CI −41.8 to 91.5; p = 0.075). These effects were paralleled by patients' positive subjective experience on laser shoes' efficacy. There were no clinically meaningful changes in the gait measures. Conclusions These findings demonstrate the immediate efficacy of laser shoes in a controlled gait laboratory, and offer a promising intervention with potential to deliver in-home cueing for patients with FOG. Classification of evidence This study provides Class III evidence that for patients with PD, laser shoes significantly reduce FOG severity (both number and duration of FOG episodes).


Abstract CancerGeneNet (https://signor.uniroma2.it/CancerGeneNet/) is a resource that links genes that are frequently mutated in cancers to cancer phenotypes. The resource takes advantage of a curation effort aimed at embedding a large fraction of the gene products that are found altered in cancer cells into a network of causal protein relationships. Graph algorithms, in turn, allow to infer likely paths of causal interactions linking cancer associated genes to cancer phenotypes thus offering a rational framework for the design of strategies to revert disease phenotypes. CancerGeneNet bridges two interaction layers by connecting proteins whose activities are affected by cancer drivers to proteins that impact on the 'hallmarks of cancer'. In addition, CancerGeneNet annotates curated pathways that are relevant to rationalize the pathological consequences of cancer driver mutations in selected common cancers and 'MiniPathways' illustrating regulatory circuits that are frequently altered in different cancers.


An active contour based tracking framework is described that generates and integrates dynamic shape information without having to learn a priori shape constraints. This dynamic shape information is combined with dynamic photometric foreground model matching and background mismatching. Boundary based optical flow is also used to estimate the location of the object in each new frame, incorporating Procrustes shape alignment. Promising results under complex deformations of shape, varied levels of noise, and closeto-complete occlusion in complex textured backgrounds are presented.


The thesis examines recent changes in planning legislation in relation to development control in Scotland and concludes with a number of observations as to the likely future direction of planning in Scotland. Part 1 provides a number of foundation chapters on which the remainder of the study is built. These include an examination of the development of Scottish planning in the 1970's, development control and the relationship between development control and local plans. Part 2 examines the legislative changes themselves by firstly looking at the philosophy of the present Conservative Government which came to power in 1979, and secondly, how that philosophy has been implemented through the changes. The area of structure plan approval is also briefly examined in order to highlight the fact that it is not only in development control that the government have made an impact. Finally, the changes are evaluated by comparing what has been done with the declared philosophy of the government. A number of failings and contradictions are identified. Part 3 takes a much broader scope by raising the question of alternative development control systems to the one already in existence in Scotland. Different systems are examined along a continuum of discretion and the link is made between one of these systems, recent literature on the subject and the developments described in Part 2. The working of such a system is examined in detail, that of zoning in Ontario, Canada. The thesis ends by concluding that the development control system in Scotland, given recent changes, is on the brink of a radical transformation towards a more zoning based system which would reduce discretion but increase certainty to the developer. Future development, however, is closely linked to what happens in the rest of the country. The advantages and disadvantages of such a transformation are discussed and it is suggested the likely implications should be strong enough to discourage this.


Gender is an issue that has been noticeably on the agenda of refugee support organisations like the United Nations High Commission for Refugees since the 1970s. With feminists pushing for change within the structures of these organisations and the modification of their focuses to include issues of gender, governmental and nongovernmental organisations soon found the issue of 'gender' and 'gender equality' one that required much attention – as well as one that would often be overshadowed by issues that were deemed more 'important' or 'pressing'. Due to the nature of the topic – large numbers of refugees fleeing from war zones or zones of ongoing conflict – it is not surprising that much of the work within the academic field of Refugee and Migration Studies has thus been preoccupied with notions of immediate survival among refugees – much attention has therefore been given to issues such as food, water, shelter and increasingly, human security. These examinations, however, tend to either neglect the issue of gender completely, or render a misguided understanding of 'gender' as synonymous to 'women'; indeed, it is thus often used as a term to refer to women and so-called 'women's issues'. Yet gender, referring to the constructed social and cultural notions of femininity and masculinity could be seen as fundamental to the experience of being a refugee. Indeed, it is posited here that issues of gender are influential in determining which individuals are capable and are 'socially accepted' to leave their home and flee the country, as well as dictating which individuals survive refugee camps and are then able to seek asylum. Gender, for instance, often dictates the levels of education that girls and women in certain countries may attain – higher levels of education, for instance, thus tend to encourage women to continue their quest for safety even if they are not accompanied by male relatives or partners. It is therefore not surprising that women who end up claiming asylum also tend to demonstrate higher levels of education generally. [2]


Purpose: In developing countries such as South Africa, many organisations are reliant on information and communication technology (ICT) to provide accurate, relevant and timely information. For organisations to obtain and sustain a competitive advantage, ICT systems are constantly implemented, upgraded, modified or replaced. These initiatives are often managed as projects. While there is an increasing amount of both financial resources and effort being spent on ICT, these projects are not always delivered within the predetermined project constraints. This implies additional time to complete, as well as additional costs, as resources are not released in time to participate in other projects. It is therefore important to understand the factors that influence the outcome of South African ICT projects relative to their original constraints. Problem Investigated: The goal of this article is to determine the factors that influence South African ICT projects, taking into consideration the fact that most current published research on this topic was done within the context of a developed country such as the USA and Europe. Design and/or methodology : The outcomes of ICT projects in South Africa as well as the factors that influence them were determined through an extensive survey. An analysis was done on the factors together with a correlation between the main factors contributing to project outcomes. The purpose of this was to establish if a factor's presence or absence influenced the eventual outcome. Findings: The factors that contribute to a successful outcome are often outside the direct control of the project manager and tend to be complex in nature. One factor that does stand out is that the alignment of projects with business objectives influences their perceived success. Originality/Value: The benefits of this article are that it firstly provides a South African perspective of current ICT project management practices, and secondly, it highlights factors that influence project outcome. Organisations can use this information to improve their current practices. Conclusion: The value of the research results presented in this paper lies in the realisation that project success is not just determined by adherence to best practices or formal processes, but requires an environment and context conducive to business success.


In recer1t years, producers of many agricultural products have become more involved in promoting their products. Morrison (1984) reports that the total costs of generic advertising of agricultural products tripled between 1972 and· 1982. During the same period, expenditures by agricultural prodcers for generic advertising of non-citrus fruits (including apples) increased from $2.2 to $15.2 million. Many other forms of advertising are used to promote sales of agricultural products. These include advertising of various brands of specific agricultural products by retailers via local newspapers; radio and television, and magazines (to a lesser extent). Local newspapers are an important vehicle for ail types of advertising. Between the mid-1970s and the mid-1980s, newspapers have accounted for approximately one-fourth of all advertising expenditures (U.S. Department of Commerce, 1987). Local newspapers account for a significant amount of food· advertisements. In 1985, local newspapers accounted 17 percent of all food marketing advertising (U.S. Department of Agriculture, February 1987). The purpose of this study was to examine the extent and type of advertising for fresh apples included in retail food ads in selected newspapers in North Carolina. Particular interest existed in identifying · specific apple characteristics retailers selected to emphasize in their newspaper promotions. Also of interest was determining whether the type of information used by retailers to promote apples changed over time or differed in two cities in North Carolina. The results of this study are intended to provide background information to producers, retailers and other parties interested in fresh apple promotion in North Carolina


The synergy of nonorthogonal multiple access (NOMA) and cognitive radio (CR) can provide efficient spectrum utilization for future wireless networks and enable supporting heterogeneous quality of service (QoS) requirements. In this context, this article aims at evaluating the throughput of a downlink CR-NOMA network where the secondary user (SU) data is opportunistically multiplexed with the primary user (PU) data using power-domain NOMA. The data multiplexing process is constrained by the PU QoS requirements. The multiplexing process can be considered seamless with respect to the PU because its receiver design will generally remain unchanged. Moreover, we consider the case where the SU detects its own data by blindly identifying the adopted transmission mode (TM) at the base station, which can be PU orthogonal multiple access PU-OMA, SU-OMA, PU/SU-NOMA, and no transmission. Consequently, the network can be classified as a hybrid underlay-interweave. The detection process is considered blind because the SU does not receive side information about the adopted TM. The obtained analytical results corroborated by Monte Carlo simulation results show that the proposed CR-NOMA network can provide substantial throughput improvement over conventional NOMA networks, particularly at low signal-to-noise ratios (SNRs) because the unutilized PU spectrum can be used by the SU. Moreover, in good channel conditions the PU can tolerate some interference from the SU, which may improve the channel utilization significantly.


The times has made human needs are increasing, including information needs. Therefore, sending and storing data through electronic media requires a process that is able to guarantee the security and integrity of the data that requires an encoding process. Encryption is the process of changing an original data into confidential data that cannot be read. Meanwhile, the decryption process is a process where the confidential data received will be converted back into the original data. In this case the Advanced Encryption Standard (AES) algorithm is used as the latest cryptographic algorithm standard. The previous algorithm was considered unable to answer the challenges of the development of communication technology very quickly. AES is a cryptographic algorithm using the Rijndael algorithm that can encrypt and decrypt blocks of data over 128 bits with a key length of 128 bits. In this study the application of AES as a file security system is carried out, where the encryption and decryption process is carried out on the file. In testing the system a trial is performed on all files with different file sizes and for the results of the encryption process (ciphertext) in the form of files with the file format with the *.encrypted extension.


Amongst the many innovations of the digital industry have been systems termed "smart green", "cleanweb" or "Sustainability by ICT" that enable more sustainable patterns of production and consumption. The field of ICT for Sustainability (ICT4S) has developed conceptualisations of these systems such as the LES Model that describes their "enabling impacts" upon production and consumption. However, initial action research amongst cleanweb startups suggested that important groups of smart green system are not distinguished by existing conceptualisations, notably the highly social systems with many interacting users, and the systems that support the adoption of more sustainable products. To address these limitations with existing conceptualisations of ICT4S, a qualitative analysis was undertaken of cleanweb companies, mapping out the range of possibilities being explored by the industry. 500 company descriptions were analysed, primarily from the CrunchBase online database. A list of search terms was developed to identify the most relevant companies. Significant characteristics of the companies were coded, and the codes were then sorted and resorted to identify higher-level concepts and categories, refined by classifying new samples, and modelled by diagramming. The result, and main contribution, is a typology of the enabling impacts of smart green systems termed the "Smart Green Map" (SGM) that organises them along five dimensions. Digital systems were found to decouple resource use either by "saving" resources directly through efficiency, or otherwise indirectly by "pushing cleantech" i.e. enhancing the adoption, construction and operation of more sustainable products. This dichotomy forms a dimension of the SGM called "Decoupling Directness". The contrasting mechanisms of "saving" and "pushing" were modelled with the LES Model's resource-use hierarchy theory. The new "push" category of enabling impacts of DDS was not clearly distinguished by established conceptualisations of ICT4S. These push impacts work by actually increasing consumption of certain products such as solar panels, bicycles, or home insulation. A fresh sample of cleanweb companies and ICT4S research papers was then classified with the SGM, to assess its utility for research. Classification by Decoupling Directness found that, as hypothesised, whilst "push systems" comprised half of the startups, they made up only 18% of research papers. Digital systems were found to combine people and digital technology in four contrasting ways, termed the "Enablers": "Automation" is purely technological with little human involvement; "Augmentation" supports and shapes the actions of one main user; "Coordination" supports the communication, interaction and collective action of many users; whilst "Autination" – a term proposed here for "automated coordination" – automates interactions between human actors. These four Enablers are the cells of a 2x2 matrix whose axes are "level of automation" and "level of social interaction", two further dimensions of the SGM. A venture capital firm has used the Enablers as the basis for their investment framework, informing decisions and communicating policies to investors and the wider market, as described in a case study. The processes of production and consumption by which resource use is decoupled were best described as part of the Circular Economy. These processes form a further dimension of the SGM that situates recycling, reuse and maintenance within ICT4S, and Sharing Economy systems such as tool-sharing and ride-sharing platforms. The remaining dimension of the SGM is the type of resource, such as heat energy, water or materials.


To settle the discussion on the chemical formula of eglestonite, synthetic material was investigated by X-ray single crystal, neutron powder diffraction, and IR spectroscopic methods. The results show unequivocally that the chemical formula is [Hg2J3Cl302H, although no peaks attributable to the OH stretching vibration were observed in the powder IR absorption spectrum. From the good agreement between the structures of natural and synthetic eglestonite, as determined by X-ray single crystal methods, it is suggested that they have the same chemical formula. The formula of the Br-dominant isotypic mineral kadyrelite, for which Hg,(Br,Cl)20 was recently proposed, should also probably be modified to [Hg2J3(Br,Cl),o2H.


The work presents the results of the study of experimental Mycoplasma pneumoniae infection in guinea-pigs. A considerable increase in the engulfment of mycoplasmas and blood leukocytes was found to occur on days 14-28 after the infection. The correlation between the degree of the engulfment of mycoplasmas by macrophages and the activity of lymphocytes in the reaction of blast-cell transformation with phytohemagglutinin and Mycoplasma antigen was observed. The peculiarities of the course of infection in sensitized animals were revealed. Virulent Mycoplasma pneumoniae strains were found to have a toxic effect on the lymphocytes and macrophages of guinea-pigs. This effect was neutralized by specific antiserum. The importance of these facts for the pathogenesis of Mycoplasma infection is discussed.


Postnatal psychological well-being is a complex issue characterized by major changes in physical, social, and emotional health. In response to addressing limitations of previous research this study aimed to: (i) quantify psychological distress, depression, anxiety, and stress in a large sample of Australian and New Zealand mothers and to compare to Australian norm data; and (ii) identify any significant differences in psychological distress, depression, anxiety, and stress of the mothers when grouped according to their self-reported exercise incidence. Self-reported short-form version Depression Anxiety Stress Scale data were collected from 3601 Australia and New Zealand mothers with at least one child under the age of 5 years. Results demonstrated that this sample of mothers had significantly poorer psychological well-being than the general Australian population. Furthermore, with the exception of anxiety, psychological well-being of mothers who reported exercising three to four times per week was significantly and meaningfully more positive compared to those mothers that reported not to exercise.


Abstract. Mapping of burned areas caused by forest fires was always a main concern to researchers in the field of remote sensing. Thus, various spectral indices and classification techniques have been proposed in the literature. In such a problem, only one specific class is of real interest and could be referred to as a one-class classification problem. One-class classification methods are highly desirable for quick mapping of classes of interest. A common used solution to deal with One-Class classification problem is based on oneclass support vector machine (OC-SVM). This method has proved useful in classification of remote sensing images. However, overfitting problem and difficulty in tuning parameters have become the major obstacles for this method. The new Presence and Background Learning (PBL) framework does not require complicated model selection and can generate very high accuracy results. On the other hand the Google Earth Engine (GEE) portal provides access to satellite and other ancillary data, cloud computing, and algorithms for processing large amounts of data with relative ease. Therefore, this study mainly aims to investigate the possibility of using the PBL framework within the GEE platform to extract burned areas from freely available Landsat archive in the year 2015. The quality of the results obtained using PBL framework was assessed using ground truth digitized by qualified technicians and compared to other classification techniques: Thresholding burned area spectral Index (BAI) and OC-SVM classifiers. Experimental results demonstrate that PBL framework for mapping the burned areas shows the higher classification accuracy than the other classifiers, and it highlights the suitability for the cases with few positive labelled samples available, which facilitates the tedious work of manual digitizing.


On the basis of the experimental data we suggest that the differences discovered in certain amino acids concentrations in blood plasma, red blood cells and tumors are criteria in early diagnostics of primary cancerous growth as well as in estimation of the efficacy of specific cancer treatment. Clinical studies on biological fluids and tumors of 1,495 patients with cancer of the mammary gland, lungs, prostate, ovaries, bladder or digestive tract showed significant changes in physiological concentrations of amino acids which either directly or indirectly regulate processes of antitumor response, oncogenesis, immunogenesis and apoptosis were shown. Our strategy of application of amino acids as medicinal preparations includes a targeted effect on the functional and metabolic relationships which are changed in specific pathology through the effect on the regulatory mechanisms of intermediate metabolic reactions, limiting stages of metabolic flows, utilization of energy substrates and transport systems restricting the processes of amino acids pool formation. The creation methodology of pathogenetic compositions of amino acids and their derivatives on the basis of their physiological concentration for practical application of their regulatory effects in oncology was discussed.


Overuse of hospital outpatient clinics in Egypt, due to lack of an effective gatekeeper system, has threatened the sustainability of improved primary care services. In this pilot project in Menoufia in the Nile delta region, the price of direct hospital outpatient visits was increased, encouraging patients to attend primary care clinics first. As a result, direct hospital outpatient utilization decreased by 63% in the project area compared with a 4% increase in a control district. The majority of this reduction was accounted for by patients attending either public primary care clinics or private clinics. Increasing the price of direct hospital outpatient visits was an effective way to establish a gatekeeper role for family health clinics.


Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.


In this study we focus on the use of coral Porites Lutea and the various treatments used to remove proteins while assessing the impact of the various removal methods on the in vitro and in vivo coral behavior. No significant differences were observed in vitro among all materials. In vivo, no histological differences were observed between BiocoralÒ and samples treated by either hydrogen peroxide or a thermal procedure. The implants made from supercritical fluid treated coral were more resistant to resorption (50% more resistant after one month).


Meticulous anatomical knowledge is mandatory to approach endoscopically the frontal sinus area safely and manage its diseases successfully. The aim of this study was to identify the various drainage patterns of the frontal sinus. To illustrate these patterns we performed anatomical dissections of the outflow tract of the frontal sinus in 30 cadaver half heads. We found that the frontal sinus drained anterior to the uncinate process in 23.3% of specimens and posterior to it in 63.3%, while it drained medial to the semilunar hiatus in 6.6%. Our study, however, represents an exclusive assortment of linear and angular measurements of important landmarks around the frontal recess region. Although these measurements were made in embalmed tissue, we believe they will provide reference points in endoscopic sinus surgery.


Abstract Direct representation of the free surface in ocean circulation models leads to a number of computational difficulties that are due to the fast time scales associated with free-surface waves. These fast time scales generally result in severe time-step restrictions when the free surface is advanced using an explicit scheme and may result in large phase errors when the free surface is treated implicitly with a large time step. A multiple-scale analysis of the shallow-water equations is used to analyze this stiffness and to guide the construction of a computational methodology that overcomes the associated difficulties. Specifically, we explore a class of fractional step methods that utilize coarsened grids in the propagation of long-wave data. The behavior of the corresponding schemes is examined in detail in light of one-dimensional model problems, based on finite-difference or spectral-element discretizations.


The objective of this note is to set out the specification of a quite general member of McFadden's (1981) GEV family of models and to discuss some of the relevant properties of that model.

The key value of McFadden's (1981) result was to establish that a large family of models was consistent with the 'RUM' concept of utility maximisation. The simplest members of that family were the MNL models, for which this consistency had already been known for a few years. The GEV result was also immediately applied to show the consistency of the 'tree logit' model with RUM, a result that was also proved at around the same time by other researchers independently of GEV theory.

Although McFadden indicated further possibilities for the GEV concept, applications of these were slow to materialise, primarily because specialised software was not available and general-purpose software, in particular Gauss, was too slow on the computers of the time to be used for serious modelling. However, in recent years applications have been made: the Paired Comparisons Logit (PCL, Koppelman and Wen, 2000), Cross-Nested Logit (CNL, McFadden, 1981, Vovsha, 1997), Generalised Nested Logit (GNL, Wen and Koppelman, 2000) and Ordered Generalised Extreme Value (OGEV, Small 1987). It is interesting to note that all of these models are of two-level structures: that is, elementary alternatives combine in 'nests' to form composite alternatives (in various ways); choice is then represented as a two stage process of choosing between these nests and then within them. The sole exception to this that has been found in the recent literature is Bhat's (1998) model in which an OGEV is 'grafted' onto the bottom of an MNL model to give a three-level structure. In each case the GEV function has been constructed and shown to satisfy McFadden's requirements, thus showing that the model is consistent with utility maximisation.

In contrast, tree logit models have long been known and even occasionally used in structures with multiple levels. Indefinite structures can be specified and even programmed efficiently (Daly, 1987).

A paper by Dagsvik (1994) indicates that there is a huge variety of GEV models, fitting effectively every possible RUM structure. However, neither Dagsvik nor McFadden indicate how GEV models should be constructed to meet specific requirements.

Recent research appears to be moving away from further exploitation of the GEV family, focussing instead on models of the 'mixed logit' family, which are in many cases easier to construct to meet specific requirements, as McFadden (2000) points out. However, GEV models still offer considerable advantages.

− In GEV models it is much quicker to calculate probabilities and their derivatives, making estimation and application much quicker than with other model forms.

− The existence of the GEV function itself is a considerable advantage for evaluation and use in further modelling.

− Several of the GEV models can be proved to converge in transport planning applications with conventional assignment procedures (see Prashker and Bekhor, 1999); it is not clear how far these proofs can be extended to more general GEV forms.

A substantial problem with GEV models is that it is necessary to specify the structure in advance in order to be able to work with them. Thus when the structure is at issue this family is not as convenient as those in which the significance of several structural elements can be tested simultaneously. For these reasons it is desirable to be able to write down GEV models with pre-defined properties.

In this note a model is presented which generalises all of the GEV models presented in the literature listed above, as well as generalising a multi-level tree logit model. This is achieved by specifying a recursive nesting structure that allows cross-nesting.

The Recursive Nested Extreme Value (RNEV) model can be specified with a wide range of cross-elasticity properties to fit a wide range of circumstances. The means by which this can be achieved are discussed in Section 3. The fact that this model generalises several other models means that its properties can be used to derive the properties of its special cases.

A further advantage of this models is that there exists an efficient estimation procedure, based on a generalisation – itself useful – of the tree logit estimation method of Daly (1987). This procedure is also discussed. It offers an efficient estimation method, using first and true second derivatives of the likelihood function, for the RNEV model itself and of course for its special cases. These special cases have been estimated by much less efficient means to date, impairing their applicability substantially. The estimation procedure is outlined in Section 4.


Evolution of domain structures across the martensitic transition (Tm) in the ferromagnetic shape memory alloy system Ni-Mn-Ga is studied using an optical microscope with a temperature variation. Compositions chosen have Tm < Tc, Tm = Tc and Tm > Tc, (Tc=Curie temperature) so that one can compare the nature of martensitic domains. There are no appreciable domain structures when Tm < Tc as compared to the one with Tm > Tc. However, giant morphological changes in the form of appearance of well-developed domains that are propagating with different directions are seen for the composition in which Tm=Tc. The results are discussed in the light of Magnetic Force Microscopy observations as well as giant entropy changes known to occur on samples with co-occurrence of Tm and Tc.


Since the 1990s, three discrete groups of aficionados have contributed to an insatiable demand for didjeridus (didgeridoos) in Australia and abroad, prompting environmental stewards (a fourth contesting camp) to promote responsible manufacture and trade to combat forest clear-felling and oversupplies of ersatz (inferior) didjeridus. A critical examination of the sourcing and construction of didjeridus harvested in the Top End of the Northern Territory and the Goldfields and Mid West Regions of Western Australia compares the effectiveness of licensing operative in these two states to regulate stem harvesting. In view of a second, more long-term concern — based on scientific prediction that some species of the hitherto adaptable genus, Eucalyptus, will succumb to global warming — the factoring of climate change into the sustainability equation flags future patterns of change in the instrument's material use and sonic production. Western Australian musician Mark Cain has explored novel ways of making and playing didjeridus. But can alternative materials satisfactorily replace rich eucalypt sonorities? Could the didjeridu — as a symbol of 'dos' and 'don'ts' — become a vital emblem for the conservation of natural ecosystems?


Background Fc receptors for IgG (Fcg R) play important roles in immune complex (IC)-mediated inflammation. Studies abrogating Fcg R actions have shown reduction of disease activity in animal models of arthritis. Monocytes are precursor cells of macrophages and osteoclasts, cell types that are highly involved in joint inflammation processes in rheumatoid arthritis (RA). We have investigated if antibody levels and monocytic Fc receptor expression and function in early RA are affected by anti-rheumatic treatment. Objectives Twenty sero-positive steroid- and DMARD naive early RA patients and thirty-three healthy controls (HC), gender- and age-matched, were included. The majority of patients were anti-citrullinated protein antibody (ACPA) positive. If not contraindicated treatment with Methotrexate + steroids was initiated. Patients were evaluated before and after 3-4 months of therapy. At follow up patients were grouped in good responders or non responders using EULAR response criteria. Methods Inflammatory laboratory parameters and immunoglobulins (Ig) were analyzed at the Akademiska University hospital laboratory with standardized procedures. Expression of Fc receptor for IgA (CD89) and IgG (FcγRIII, CD16; FcγRIIa, CD32a; FcγRIIb, CD32b; FcγRI, CD64) on CD14 positive monocytes were analyzed with flow cytometry. Fcg R function was evaluated with IgG1 and IgG3 immune complex (IC) binding and IgG stimulated TNFa -production. DAS28, HAQ and patient reported VAS-scores for pain, global assessment and morning stiffness defined disease activity. Results At inclusion RA patients displayed elevated levels of total IgG, IgG1 and IgG3 compared to HC. Expression of CD64 (frequency of cells and mean fluorescence intensity) and surface bound IgG on CD64 positive cells were significantly increased in RA patients. The Fcg R function in the patients was altered: a decrease in IC binding was observed, but monocytic TNFa -production was comparable with HC, except for non-responders who at baseline presented lower TNFa release when stimulated with IgG1. IgG and IgA levels correlated positively with the number of CD64/CD16 positive monocytes. Fc receptor expressions and function correlated with disease activity parameters. ACPA levels showed no correlations with FcR expressions or disease activity parameters. At follow up mean DAS28 had decreased from 5.26 to 3.65 and mean HAQ from 0.95 to 0.45. The patients presented with significantly decreased levels of total Ig isotypes, IgG subclasses, ACPA and rheumatoid factor (RF) isotypes. Good responders excelled by down regulating CD64, decreasing CD16 on CD64 positive cells and increasing CD89. These results were not obtained in non-responders who instead increased the number of CD16 positive cells and CD64 positive cells. Interestingly, the monocytic expression of the inhibitory Fcg R (CD32b) was higher in good responders compared with non-responders at follow up. Conclusions Monocytic Fc receptor status is altered in early RA. Especially CD64 seems to be important. Successful response to standard anti-rheumatic treatment downregulates its expression. Disclosure of Interest None Declared


Objective With the use of teleconferencing for grant peer-review panels increasing, further studies are necessary to determine the efficacy of the teleconference setting compared to the traditional onsite/face-to-face setting. The objective of this analysis was to examine the effects of discussion, namely changes in application scoring premeeting and postdiscussion, in these settings. We also investigated other parameters, including the magnitude of score shifts and application discussion time in face-to-face and teleconference review settings. Design The investigation involved a retrospective, quantitative analysis of premeeting and postdiscussion scores and discussion times for teleconference and face-to-face review panels. The analysis included 260 and 212 application score data points and 212 and 171 discussion time data points for the face-to-face and teleconference settings, respectively. Results The effect of discussion was found to be small, on average, in both settings. However, discussion was found to be important for at least 10% of applications, regardless of setting, with these applications moving over a potential funding line in either direction (fundable to unfundable or vice versa). Small differences were uncovered relating to the effect of discussion between settings, including a decrease in the magnitude of the effect in the teleconference panels as compared to face-to-face. Discussion time (despite teleconferences having shorter discussions) was observed to have little influence on the magnitude of the effect of discussion. Additionally, panel discussion was found to often result in a poorer score (as opposed to an improvement) when compared to reviewer premeeting scores. This was true regardless of setting or assigned reviewer type (primary or secondary reviewer). Conclusions Subtle differences were observed between settings, potentially due to reduced engagement in teleconferences. Overall, further research is required on the psychology of decision-making, team performance and persuasion to better elucidate the group dynamics of telephonic and virtual ad-hoc peer-review panels.


Dissolved organic matter (DOM) is an important factor in aquatic ecosystems, which is involved in a large variety of biogeochemical and ecological processes, and recent literature suggests that it could be strongly affected by agriculture in different climates. Based on novel monitoring techniques, we investigated the interaction of climate and agriculture effects on DOM quantity and quality. To examine this, we took water samples over 2 years in two paired intensive and extensive farming catchments in each of Denmark (temperate climate) and Uruguay (subtropical climate). We measured dissolved organic carbon (DOC) and nitrogen (DON) concentrations and DOC and DON molecular fractions with size-exclusion chromatography. Moreover, we characterized DOM quality with absorbance and fluorescence measurements, as well as parallel factor analysis (PARAFAC). We also calculated the DOC and DON loads based on daily discharge measurements, as well as measured precipitation and air temperature. The fluvial DOM in the catchments in Uruguay was characterized by higher temporal variability of DOC and DON loads which were clearly to a higher temporal variability of precipitation and a DOM composition with rather plant-like character relative to the Danish catchments. Moreover, we found a consistently higher temporal variability of DOC and DON loads in the intensive farming catchments than in the extensive farming catchments, with highest temporal variability in the Uruguayan intensive farming catchment. Furthermore, the composition of DOM exported from the intensive farming catchments was consistently complex and always related to microbial processing in both Denmark and Uruguay. This was indicated by low C : N ratios, several spectroscopic DOM composition indices and PARAFAC fluorescence components. We propose that the consistent effect of intensive farming on DOM composition and the temporal variability of DOC and DON loads is related to similarities in the management of agriculture, which may have widescale implications for fluvial DOM composition, as well as related ecological processes and biogeochemical cycles.


Inhibition of carbonic anhydrase III (CA III; EC 184.108.40.206 ) activity in type I muscle can influence resistance to fatigue and glycogen utilization. Our aim was to determine if CA III inhibition could influence muscle pH and glycolytic rate. Muscle pH, hexosemonophosphates (HMP), glycolytic intermediates, ATP, and creatine phosphate (CP) were measured at rest and during a fatigue protocol in rat soleus muscles in vitro with or without CA inhibitors (CAI). In resting muscles, CAI resulted in a significant drop in pH (7.11 vs. 7.06, P < 0.05) and in a two- to threefold increase in HMP content compared with control muscles. Measurements of HMP and glycolytic intermediates during the fatigue protocol suggested, however, that the glycolytic flux was not influenced. Globally, muscles incubated with CAI showed larger perturbations of their CP and ATP content than control muscles. The accumulation of HMP induced by the CAI was found to be totally dependent on the combined presence of external glucose and contractile activity, suggesting that inhibiting CA III may augment the responsitivity of the contraction-induced glucose uptake process.


In 2010, the first economic adjustment program began offering a blueprint for economic recovery and a feasible way for Greece to emerge from the crisis. The authors show that Greece neither overcame its structural weaknesses nor developed export industries as a driver of growth in the course of reforms, and they conclude that Greece's sectoral structures still mirror a low level of industrial development as well as a service industry with a below-average growth performance compared to other EU countries. Greece's composition of exports exhibits a limited growth and value-added potential, and is similar to the export patterns of low-income countries due to a focus on raw materials and labor-intensive goods. The analysis also shows that without significant growth, the Greek debt will remain unsustainable. A haircut or a phasing out of the debt burden can only complement supply-oriented structural reforms, however. The reform agenda of August 2015 is a new attempt to implement the reforms that the creditors have been waiting on for the past five years.


The first type of IR microscope to be developed, and still in general use, provides optical visualisation plus IR spectroscopic data collection. Its essential features include: 1. reflective optics for focusing, collecting, and imaging transmitted or reflected IR radiation from the sample onto a detector, 2. one or more variable apertures located in an image plane of the sample which serve to define the area to be recorded, and 3. a visible light path which is parfocal and collinear with the IR light path so that the sample can be viewed and positioned. The accessory is coupled to a Fourier transform IR (FTIR) spectrometer by a set of transfer optics from the interferometer into the microscope. The analyst is thus provided with the capability to perform IR transmission, absorption-reflection, specular reflection, and diffuse reflection experiments on microscopic samples. Using special microscope objectives or accessories, attenuated total reflection (ATR) and grazing angle reflection experiments can be performed as well. IR microspectroscopy can also be used to map a sample's heterogeneity using a motorized stage in conjunction with a standard mercury cadmium telluride (MCT) detector. Alternatively, the second (more recent and more advanced) technique employs focal plane array (FPA) detection coupled with step-scan interferometry for IR chemical imaging, where the image contrast is determined by the response of individual sample regions to particular IR wavelengths selected by the user. Thus spatial and spectral information can be collected simultaneously. The superior contrast attained by functional group imaging and the selectivity found in the mid-IR region has been shown to be a powerful analytical tool. However, diffraction ultimately limits the quality of the spectral information obtained, and its effects may include poor spatial resolution, a reduction in photometric accuracy, and unreliable band intensities. Furthermore, unwanted optical effects from microscopic samples can also affect the quality of the spectrum, and sample preparation techniques must often take into account a sample's thickness, diameter, refractive index, and shape. These limitations have to some extent been circumvented by the development of near-field techniques such as scanning near-field optical microscopy (SNOM), IR apertureless scattering SNOM (s-SNOM), photothermal microspectroscopy (PTMS), and atomic force microsopy-IR (AFM-IR, alternatively known as photothermally-induced resonance, PTIR). IR microscopes that rely on near-field imaging have not yet become "standard" technology but are increasingly coming into use.


Since its first description by Guido Fanconi in 1927,1 Fanconi anemia (FA) has become one of the best characterized inherited bone marrow failure syndromes.2–3 Numerous studies over the years have documented its clinical and biological features. It is recognized as being clinically heterogeneous and patients can have a wide range of developmental abnormalities. Many patients develop progressive bone marrow failure and there is a high predisposition to cancer. FA cells characteristically display a high frequency of spontaneous chromosomal breakage and hypersensitivity to DNA cross-linking agents4 such as mitomycin C and diepoxybutane. This FA cell hallmark has facilitated diagnosis in the clinic and scientific advances in the laboratory.

FA is now known to be caused by biallelic mutations in one of 15 genes, the products of which interact in the FA/BRCA pathway in response to cellular stress and DNA damage to maintain genomic stability.5 FA can, therefore, be regarded as an inherited DNA repair disorder. Despite these advances, the precise pathophysiology of the bone marrow failure in FA has remained elusive.

A recent international study by Ceccaldi and colleagues6 now provides new insights into the pathogenesis of bone marrow failure in FA. They analyzed bone marrow samples from a large number of FA patients and controls. By undertaking quantitative and qualitative assessment of hematopoietic function they established that FA patients have a significant impairment of hematopoiesis that begins early and is progressive throughout life. In view of the DNA repair defect that has been observed in FA cells, together with the observation that p53 plays an important role in the response to DNA damage, Ceccaldi and colleagues6 decided to analyze p53. They found strong basal and mitomycin C-induced p53 expression in primary cells from FA patients and in bone marrow cells of FA mouse (Fancg−/− and Fancd2−/−) models. To confirm that the p53 induction was directly related to the FA/BRCA pathway defect they knocked down FANCD2 (a key target of the FA pathway) in a human cell line (293T cells) and observed that p53, as well as p21, was induced in these cells. To mimic the response of FA cells to endogenous DNA damage, and to determine the link to the progressive cell impairment observed in patients, they exposed EBV-immortalized FA cells to interstrand cross-linking agents and studied the cellular response at several time points. These EBV-immortalized FA cells displayed the classic excess G2 arrest at 24 h; however, at later time points the G2 arrest resolved and the cells shifted to G0/G1 cell cycle arrest. Interestingly, in p53-silenced FA cells, p21 induction and G0/G1 accumulation were less marked. Complementary studies in FA mice showed that p53 impairs the hematopoietic and mitotic potential of Fanc-deficient murine hematopoietic stem and progenitor cells. Additional studies (including on bone marrow from young FA patients and fetal liver of FA patients) demonstrated constitutive activation of p53 and p21 as well as G0/G1 cell cycle arrest in hematopoietic progenitor cells in vivo.

In conclusion, this study identifies an exacerbated p53/p21 DNA damage response as an important factor in the progressive impairment of hematopoiesis in FA; this begins prenatally and typically results in overt bone marrow failure in childhood. These new observations have important implications for the management of FA patients.


Sodium-rich hydrothermal alteration is widely developed in Permian to Jurassic arc igneous rocks of the western United States, but it is rare in younger rocks. Na-rich alteration reflects a paleogeographic control on development. Two varieties, NaCa and Na, can be defined by mineralogic and compositional changes. Both are common in Permian to Jurassic arc plutonic and volcanic rocks and are accompanied by Fe and Cu ± Zn mineralization. Geologic relations and mineralogic, stable isotopic, and fluid-inclusion data indicate that the fluids responsible for sodium-rich alteration were isotopically heavy, moderately to highly saline fluids of marine, formation, and/or meteoric origin, with or without a magmatic component. The transition away from widespread Na ± Ca-rich alteration in the late Mesozoic corresponds to and is consistent with the change from an early Mesozoic marine and/or arid rifted arc setting to a fully emergent, continental arc environment in the Cretaceous.


The solubility of polymer nanoparticles is a complex phenomenon dependent on solvent–solute and solute–solute interactions. Contrary to phase separation in standard polymerization reactions, which is a well established research area, the relationship between the solubility of polymer nanoparticles and the resulting diameter of the nanoparticles has been largely overlooked. Herein we demonstrate that the absolute size of polymer nanoparticles can be predicted (and controlled) by varying the relevant parameters of the polymerization conditions that influence the solubility and Flory parameter, χs, p. The position of the spinodal, associated with a given χs, p equivalent and determined with a simple thermodynamic model, allows an absolute value, Δχspinodal, to be applied in predicting polymer dimensions. The hydrodynamic diameter of particles at the primarily observed fraction was found to be dependent on D (nm) = −74Δχspinodal + 367 nm, where Δχspinodal must be positive for successful separation. Variation with total polymer fraction over a limited range can also be observed to follow a trend of approximately D (nm) = 173 ln[(xN)210−36/Δχspinodal] − 193 nm, thus giving a more general description of polymerization. We also assert the importance of separating spinodal-character phase separation from binodal-character phase separation in polymer nanoparticle synthesis. To the best of our knowledge this is the first successful Flory–Huggins based thermodynamic model of polymer nanoparticles, and should provide a useful guide to predictive design of future nanomaterials.


Serviceability limit states require that cracking of reinforced concrete members be controlled for appearance, leaking, and durability requirements. The calculation of crack width in glass fiber–reinforced polymer (GFRP)-reinforced concrete flexural members is dependent on many factors, such as concrete cover, bar spacing, bar tensile stress, and bond-dependent coefficient (kb), which accounts for the bar surface condition. This article presents the determination of the bond-dependent coefficient (kb) for helically wrapped sand-coated deformed GFRP bars. A total of six beams were fabricated and tested for three different diameters of GFRP bars: #4 (13 mm), #6 (19 mm), and #8 (25 mm). The calculated values were compared against the proposed values according to ACI 440.1R, Guide for the Design and Construction of Structural Concrete Reinforced with Fiber-Reinforced Polymer Bars, and CAN/CSA S806, Design and Construction of Building Structures with Fibre-Reinforced Polymers. The average kb value of the tested GFRP bars was found to be 1, which indicates similar bond behavior to deformed steel bars. Also, the kb values proposed in ACI 440.1R overestimate crack width, while kb values proposed in CAN/CSA S806 are close to the ones obtained from the tested GFRP bars.


The article uses a single theoretical framework to analyze the development of participatory organizational forms. The histories of decision-making structures are considered in terms of the structural sources of decision-making power within organizations and supraorganizational networks. The dialectic of power at the points of production and managerial planning lead to distinct forms of authority and structures of workforce participation in the decision-making process. Structural linkages between forms of industrial organization, ownership, and development and growth of corporate structure and workforce participation in decision-making are the central issues examined. Principal conclusions of the analysis are that collective bargaining, as developed within capitalism, is a form of workers' participation and that worker ownership is a necessary but not sufficient condition of workers' control.


Purpose: Estrogen-responsive finger protein (Efp) is a member of RING finger-B box-Coiled Coil family and is also a downstream target of estrogen receptor α. Previously, Efp was shown to mediate estrogen-induced cell growth, which suggests possible involvement in the development of human breast carcinomas. In this study, we examined expression of Efp in breast carcinoma tissues and correlated these findings with various clinicopathologic variables. Experimental Design: Thirty frozen specimens of breast carcinomas were used for immunohistochemistry and laser capture microdissection/real-time PCR of Efp. Immunohistochemistry for Efp was also done in 151 breast carcinoma specimens fixed with formalin and embedded in paraffin wax. Results: Efp immunoreactivity was detected in breast carcinoma cells and was significantly associated with the mRNA level (n = 30). Efp immunoreactivity was positively associated with lymph node status or estrogen receptor α status and negatively correlated with histologic grade or 14-3-3σ immunoreactivity (n = 151). Moreover, Efp immunoreactivity was significantly correlated with poor prognosis of breast cancer patients, and multivariate analyses of disease-free survival and overall survival for 151 breast cancer patients showed that Efp immunoreactivity was the independent marker. Conclusions: Our data suggest that Efp immunoreactivity is a significant prognostic factor in breast cancer patients. These findings may account for an oncogenic role of Efp in the tumor progression of breast carcinoma.


Industrial ecology represents an emerging interdisciplinary field of studying industrial systems in combination with their fundamental linkage with nature. An eye-catching characteristic at the basis of industrial ecology's scientific profile is its refreshingly unorthodox perspective of understanding nature as model, compared with other disciplines of understanding nature, e.g. in terms of 'sack of resources' or 'biophysical limit' as opposed to industrial systems. The idea of industrial ecology's appealing perspective is to balance the development of industrial systems with the constraints of natural ecosystems, analogous to an 'industrial symbiosis'. On the basis of initial efforts to conceptualize industrial ecology's underlying assumptions concerning nature, a philosophically focused approach of its characteristic perspective of understanding nature as model is presented. The contribution may provide industrial ecologists as well as other economists, engineers, scientists and policy-makers involved in the field of sustainability with an opportunity for accessible philosophical reflection, perhaps bringing to the surface their tacit frames regarding nature. Consequently, the goal is to gain greater conceptual clarity and to contribute to laying a solid foundation for industrial ecology's stimulating role when initiating change towards sustainability at large. Copyright © 2003 John Wiley & Sons, Ltd and ERP Environment.


Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC

Chemoprevention has received considerable attention over the last decade. The notion of using bioactive food components to reduce the risk of developing, or the recurrence of cancer has long been recognized. Resveratrol (a naturally occurring polyphenolic compound) has been studied extensively with considerable evidence demonstrating its efficacy as an anti-inflammatory and anti-cancer agent, with the most evidence for its role in colon cancer prevention. However, Resveratrol intervention studies in clinical trials still remains controversial, due to the lack of biomarkers of efficacy. Utilizing Metabolomic analysis we have identified biomarkers of efficacy in a pre-clinical model of inflammation-induced colorectal carcinogenesis.

Metabolomics is the process of identifying metabolites present in biological specimens. Our study has demonstrated the chemopreventative activity of Resveratrol in mice treated with the chemical carcinogen azoxymethane (AOM) and then exposed to colonic irritant dextran sodium sulfate (DSS) to induce inflammation-associated colon carcinogenesis. We found a diet enriched in Resveratrol resulted in a reduction in tumor incidence in AOM/DSS treated mice by 29 percent. Furthermore, we identified several biomarkers that are indicative of Resveratrol chemopreventive activities. Prior studies have shown Resveratrol's role in inhibiting several key enzymes important during the carcinogenesis process. We have correlated such findings with Metabolomic biomarkers. We found a significant reduction in Arachidonic acid, the limiting reagent of pro-inflammatory enzyme COX-2, and a reduction in spermidine a product of Ornithine decarboxylase, an enzyme that promotes proliferation. More intriguingly, we found biomarkers representing changes in bile acids by Resveratrol, which highlight chemopreventative activities that were not previously described. We found that Resveratrol treatment causes a reduction in tumorigenic secondary bile acids, deoxycholic acid and lithocholic acid, which are metabolic byproducts of intestinal bacteria. These data suggested that dietary supplementation with Resveratrol results in a healthy microbiome.

These pre-clinical studies should easily be translated into clinical studies designed to ascertain chemopreventive efficacy for bioactive compounds like Resveratrol, all with the objective to identify patients that will benefit from an intervention.

Citation Format: Shakir Saud, Matthew Young, Ed Karoly, Chris Bernard, Nancy Colburn, Young Kim. Resveratrol's Metabolomic biomarkers of efficacy: the missing link to chemoprevention. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 198. doi:10.1158/1538-7445.AM2013-198


For FeNi/FeMn bilayers, the angular dependence of exchange bias shows hysteresis between clockwise and counterclockwise rotations, as a new signature. The hysteresis decreases for thick antiferromagnet layers. Calculations have clearly shown that the orientation of antiferromagnet spins also exhibits hysteresis between clockwise and counterclockwise rotations. This furnishes an interpretation of the macroscopic behavior of the ferromagnetic layer in terms of the thermally driven evolution of the magnetic state of the antiferromagnet layer.


Islet transplantation has set the ground for diabetes cell therapy and is still undergoing various developments that might improve clinical outcomes. Alternative sources for β-cell replacement strategies are now led by human pluripotent stem cells that demonstrate near-normal β-cell features after in vitro differentiation and which can reverse diabetes in mice. Yet, their propensity for tumor formation is still unresolved. The adult pancreas is suggested as a reservoir of facultative progenitors that could represent adequate candidates for β-cell engineering, either in vivo through pharmacological treatment or after expansion in culture. This review focuses on the latest developments in protocols aiming at de novo production of functional β cells.


Should mass distribution of azithromycin be in topical rather than oral formulation?

In this issue, Cochereau et al 1 present the results of a randomised controlled trial comparing the effectiveness of topical and oral azithromycin for treatment of active trachoma in children (see page 667) .

Trachoma remains a leading cause of blindness in the world, responsible for an estimated 1.3 million cases.2 The World Health Organization (WHO) recommends the SAFE (Surgery, Antibiotics, Facial cleanliness, Environmental improvement) strategy to control blinding trachoma, which includes the distribution of antibiotics to treat the Chlamydia trachomatis infection that causes active trachoma. Until recently, the treatment of choice was topical administration of 1% tetracycline ointment twice daily for 6 weeks or on 5 consecutive days each month for 6 months. This regimen had low adherence because of the long duration of treatment and the discomfort caused by the ointment. An alternative treatment is a single oral dose of azithromycin. Observational studies suggest that oral azithromycin is highly effective at reducing active trachoma and infection with C trachomatis in the community,3–6 although evidence from randomised controlled trials is inconclusive.7

Azithromycin is costly, but, thanks to Pfizer's generous donation of the drug, mass distribution has been undertaken …