BACKGROUND
Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.

METHODS
In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).

RESULTS
A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.

CONCLUSIONS
Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).


This article considers an ongoing research project concerning the outcome of the Swedish reform of advanced vocational education (AVE) from a graduate perspective. Launched in 1996 as an experimental post-secondary reform meeting the advancements within working life, several new educational features were introduced. In January 2002, AVE became a regular part of the national education system with 12,500 education places per annum. From start to present, over 6,100 students have graduated from the approximately 350 different national AVE programmes available. The purpose of this article is to present results from three sets of questionnaires collected in 1999, 2000 and 2001 surveying over 5,400 of the graduates concerning their opinions and experiences on how AVE corresponds to the demands and requests made of them when entering the labour market. The aggregate results suggest that a majority of the graduates (82%) had a job 6 months after having completed their AVE programmes and that approximately 80% of them were working, with regard to their educational focus, within a 'target' field of profession.


Growth in human population and anthropogenic activities has increased the rate of groundwater pollution in the world. This study assessed the quality of water samples collected from open wells from eight different locations in Ilorin, North Central, Nigeria between December 2014 and June 2015. The physicochemical parameters of water samples were analyzed using standard methods. Total bacterial count and total coliform count were determined by standard plate method and membrane filtration technique respectively.  Identification of isolated bacteria was done using Bergey's Manual of Determinative Bacteriology and confirmed by sequencing the DNA of the isolates. The physicochemical values of the water samples ranged as follows: temperature (28.20±0.440C to 27.50±0.370C), pH (7.22±0.06 and 6.80±0.04), conductivity (577.80±41.28 µS/cm), turbidity (6.31±0.21 to 2.69±0.40NTU), total suspended solids (6.20±2.60 to 47.50±1.70mg/l), total dissolved solids (295.40±37.12 to 208.40±31.19 mg/l), dissolved oxygen (9.81±0.37 to 7.04±0.40mg/l), biochemical oxygen demand (6.25±1.31 to 4.38±0.28mg/l), total hardness (294.20±3.81 to 278.10±7.14mg/l), nitrate concentration (23.80±1.61 to 17.47±3.58mg/l) and sulfate concentration (30.58±2.43 to 25.35±1.16mg/l).  The water sources were found to have a total bacterial count and total coliform counts above the recommended national and international guidelines. The contamination of the water sources by E. coli and other pathogenic bacteria implies that they are not fit for human consumption.


The article copy deposited in TSpace is limited to noncommercial distributions and personal use by others. AACE is the official publisher of this work and retains copyright over it.


How could ecological thinking animate an epistemology capable of addressing feminist, multicultural, and other post-colonial concerns? Starting from an epistemological approach implicit in Rachel Carson's scientific practice, Lorraine Code elaborates the creative, restructuring resources of ecology for a theory of knowledge. She critiques the instrumental rationality, abstract individualism, and exploitation of people and places that western epistemologies of mastery have legitimated, to propose a politics of epistemic location, sensitive to the interplay of particularity and diversity, and focused on responsible epistemic practice. Drawing on ecological theory and practice, on naturalized epistemology, and on feminist and post-colonial theories, Code analyzes extended examples from developmental psychology, and from two "natural" institutions of knowledge production-medicine and law. These institutions lend themselves well to a reconfigured naturalism. They are, in practice, empirically-scientifically informed, specifically situated, and locally interpretive. With human subjects as their "objects" of knowledge, they invoke the responsibility requirements central to Code's larger project. This book discusses a wide range of literature in philosophy, social science, and ethico-political thought. Highly innovative, it will generate productive conversations in feminist theory, and in the ethics and politics of knowledge more broadly conceived.


PV applications run from field installations, to building added PV to PV integrated into building, infrastructure and landscapes. Specifically, applications of integrated PV may demand very different properties of the PV panels, such as design, shade tolerance, resistance to harsh climatic conditions and the ability to capture light under non ideal conditions. However, the solar panels in production still mainly are `one size fits all'. In this paper, ECN will present its developments towards utilizing the mass manufactured building blocks with novel module and system designs for increased application and usage.


This paper develops a general equilibrium model of multi-product firms and analyzes their behavior during trade liberalization. Firm productivity in a given product is modeled as a combination of firm-level "ability" and firmproduct-level "expertise", both of which are stochastic and unknown prior to the firm's payment of a sunk cost of entry. Higher firm-level ability raises a firm's productivity across all products, which induces a positive correlation between a firm's intensive (output per product) and extensive (number of products) margins. Trade liberalization fosters productivity growth within and across firms and in aggregate by inducing firms to shed marginally productive products and forcing the lowest-productivity firms to exit. Though exporters produce a smaller range of products after liberalization, they increase the share of products sold abroad as well as exports per product. All of these adjustments are shown to be relatively more pronounced in countries' comparative advantage industries.


We examine subhaloes and galaxies residing in a simulated Λ cold dark matter galaxy cluster (Mcrit200=1.1×1015h−1M⊙) produced by hydrodynamical codes ranging from classic smooth particle hydrodynamics (SPH), newer SPH codes, adaptive and moving mesh codes. These codes use subgrid models to capture galaxy formation physics. We compare how well these codes reproduce the same subhaloes/galaxies in gravity-only, non-radiative hydrodynamics and full feedback physics runs by looking at the overall subhalo/galaxy distribution and on an individual object basis. We find that the subhalo population is reproduced to within ≲10 per cent for both dark matter only and non-radiative runs, with individual objects showing code-to-code scatter of ≲0.1 dex, although the gas in non-radiative simulations shows significant scatter. Including feedback physics significantly increases the diversity. Subhalo mass and Vmax distributions vary by ≈20 per cent. The galaxy populations also show striking code-to-code variations. Although the Tully–Fisher relation is similar in almost all codes, the number of galaxies with 109 h− 1 M⊙ ≲ M* ≲ 1012 h− 1 M⊙ can differ by a factor of 4. Individual galaxies show code-to-code scatter of ∼0.5 dex in stellar mass. Moreover, systematic differences exist, with some codes producing galaxies 70 per cent smaller than others. The diversity partially arises from the inclusion/absence of active galactic nucleus feedback. Our results combined with our companion papers demonstrate that subgrid physics is not just subject to fine-tuning, but the complexity of building galaxies in all environments remains a challenge. We argue that even basic galaxy properties, such as stellar mass to halo mass, should be treated with errors bars of ∼0.2–0.4 dex.


Abstract Swaziland's prevention of mother-to-child transmission (PMTCT) programme is linked to maternal and newborn health (MNH) services, but is mainly focussed on HIV/AIDS. Existing MNH services are inadequate, especially postnatal care (PNC) of mothers and babies, with delayed postnatal visits occurring at 4–6 weeks after delivery. Fifty-seven percent of staff in seven Swazi health facilities were trained in promoting and providing early PNC. A final evaluation showed a 20-fold increase in the number of visits coming for an early postnatal visit (within the first three days after birth). A direct observation of the client–provider interaction showed a significant increase in the competence of the health workers related to postnatal examinations, and care of mothers and babies (p<0.05– < 0.01). The percentage of women breastfeeding within one hour of delivery increased by 41% in HIV-positive mothers and 52% in HIV-negative mothers. Cotrimoxazole prophylaxis for HIV-exposed infants increased by 24%. Although, health workers were observed providing counselling, maternal recall of messages was deficient, suggesting the need for additional strategies for promoting healthy behaviours. High-quality integrated PMTCT programmes and MNH postnatal services are feasible and acceptable, and can result in promoting early postnatal visits and improved care of both HIV-positive and HIV-negative mothers and their babies.


Survival of living organism and socioeconomic development depend largely on the availability of water. Ground water is a main source of water for irrigation, industries, recreation, domestic and drinking purpose. With the increasing population and industries, the requirement of water is increasing day by day and as industries are growing the pollutants from these are also increasing and so the quality is decreasing day by day at an alarming rate. The present study had been conducted in the Sitarganj area of Udham Singh Nagar, Uttarakhand, Indiato study the physico-chemical characteristics of water from the shallow aquifer and the extent of pollution and to judge the suitability of water for irrigation, industrial and domestic use. In this study, it was found that the shallow aquifer ground water was not safe for the drinking purpose with respect to all the parameters taken together. But it was found that water samples from most of the locations were suitable for irrigation purpose


This paper argues that in the presence of intersectoral input-output linkages, microeconomic idiosyncratic shocks may lead to aggregate fluctuations. In particular, it shows that, as the economy becomes more disaggregated, the rate at which aggregate volatility decays is determined by the structure of the network capturing such linkages. Our main results provide a characterization of this relationship in terms of the importance of different sectors as suppliers to their immediate customers as well as their role as indirect suppliers to chains of downstream sectors. Such higher-order interconnections capture the possibility of "cascade effects" whereby productivity shocks to a sector propagate not only to its immediate downstream customers, but also indirectly to the rest of the economy. Our results highlight that sizable aggregate volatility is obtained from sectoral idiosyncratic shocks only if there exists significant asymmetry in the roles that sectors play as suppliers to others, and that the "sparseness" of the input-output matrix is unrelated to the nature of aggregate fluctuations.


ABSTRACT Research evidence suggests that older immigrants' resettlement in a new host country is hindered by limited opportunities to engage within communities in deeply familiar ways, using culturally meaningful occupations. A recent study concluded that older Asian immigrants contribute to social capital; yet there is little understanding of how they go about doing so. This New Zealand study examined how older Chinese, Indian, and Korean immigrants' participation contributes to civic society. Research partnerships were established with bilingual local intermediaries, who assisted the study's design and implementation. Bilingual research assistants and translators were contracted to assist with recruitment, data gathering, and transcript translation. Recruitment was conducted through venues where older immigrant ethnic groups frequented. The 74 participants were Chinese (24), Indian (25), and Korean (25) immigrants, aged 60 to 83 years, who were aged 55 or older on arrival, and had resided in New Zealand between 1 and 19 years. Nine focus group interviews, three with each ethnic group, were conducted and analysed. Subsequently, 15 participants, five from each ethnic group, were theoretically sampled for individual interview. Three culture-specific provisional theories were developed. Similarities in the theoretical dimensions justified the analytic development of one cross-cultural theory. The resulting theory showed how their engagement with, and participation in, socially embedded older immigrant networks become a form of cultural enfranchisement and a pathway towards wider civic participation. While still largely hidden from societal view, these older immigrants found ways of giving service and strengthening community for the good of all.


A recent expansion of passenger cars' automated functions has led to increasingly challenging design problems for the engineers. Among this the development of Automated Valet Parking is the latest addition. The system represents the next evolution of automated system giving the vehicle greater autonomy: the efforts of most automotive OEMs go towards achieving market deployment of such automated function. To this end the focus of each OEM is on taking part to this competitive endeavor and succeed by developing a proprietary solution with the support of hardware and software suppliers. Within this framework the present work aims at developing an effective control strategy for the considered scenarios. In order to reach this goal a Model Predictive Control approach is employed taking advantage of previous works within the automotive OEM in the automated driving field. The control algorithm is developed in a Simulink® simulation according to the requirements of the application and tested; results show the control strategy successfully drives the vehicle on the predefined path.


This article explores the phenomenology of mothers as they return to memorable photographs. [i] It reviews research on three mothers who articulate the lived experience of photographs, and how such experience might reveal basic ontological aspects of motherhood.  The phenomenology of a mother's memorable photographs discloses an aporia of human relationships that involves the connectedness she has with her children, and the awareness that her children have become separate individuals. These two themes – separateness and coexistence – are indissolubly at odds. Each constitutes a mother's potential lived experience of photographs as viewed in front of her. A concluding discussion reviews how each of these contradictory themes provides the necessary context for the other to arise, mutually presupposing the other. [i] The Duquesne University IRB approved the research conducted in this article (Protocol #11-27). The author would like to thank Eva Simms, Patrick Howard, and two anonymous reviewers for helpful feedback while preparing this article. This article is indebted to the three mothers who participated in this research.


1. Eleven untreated men with mild to moderate primary hypertension and 10 normotensive control subjects were studied at rest and during a mental stress test (Stroop colour word conflict test), which has previously been used in studies of hypertensive patients with regard to non-invasive cardiovascular variables and venous plasma catecholamine concentrations. 2. Heart rate, central cardiovascular pressures, cardiac output (thermodilution) and forearm blood flow (strain gauge plethysmography) were determined. Systemic and forearm vascular resistances were calculated. Arterial and venous plasma adrenaline and noradrenaline concentrations were measured by h.p.l.c., and arterial noradrenaline spillover and noradrenaline overflow from the forearm were assessed by isotope methodology ([3H]noradrenaline). Neuropeptide Y-like immunoreactivity was measured by radioimmunoassay. 3. In hypertensive patients heart rate, arterial blood pressure, cardiac output and forearm blood flow increased by 28%, 13%, 37% and 115%, respectively, and forearm and systemic vascular resistances decreased by 48% and 21%, respectively (P < 0.001 for all responses), during stress. These responses were not different from those of the control group. 4. Arterial noradrenaline spillover rose by 63% and noradrenaline overflow from the forearm rose by 150% in the hypertensive patients in response to mental stress (P < 0.001); no significant group differences could be demonstrated. However, the forearm noradrenaline overflow response to stress tended to be greater in the hypertensive group (P = 0.11). Arterial adrenaline concentrations doubled in both groups (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


This article discusses the dynamics of anti-base coalition movements in South Korea, with particular attention to the role of framing. With two anti-base movement campaigns as case studies—the movement against base expansion at Camp Humphreys in Pyeongtaek, and the anti-base movement that led to the eventual closure of Kooni Firing Range in Maehyangri—the author argues that effective mobilization in anti-base movements requires striking a balance between the movements' focus on local and national issues regarding US military bases. Moreover, although political opportunity structures and mobilization resources are often given more weight within the political process model of social movements, local-national tension that exists within South
Korean anti-base movements highlights the importance of framing contention in antibase movements.


Just a few Yotes shy of entering into force, the Cartagena Protocol on Biosafety is poised to become the next multilateral environmental agreement that has the potential to pit trade interests against enYironmental concerns. Nevertheless, concerns over impending conflict with the \\'TO trade regime may be misplaced. A detailed analysis of the rights and obligations of the parties to the Protocol and the applicable \\'TO disciplines reYeals few instances of probable conflict. The United States, one of the largest exporters of LMOs, has not signed or ratified the Protocol. Thus, the determination that no conflict exists is of particular importance if the Protocol is to be effective in the likely scenario where the exporting country is not a party to the Protocol but both it and the importing country are members of the \\'TO.


In the game of Penney Ante two players take turns publicly selecting two distinct words of length $n$ using letters from an alphabet $\Omega$ of size $q$. They roll a fair $q$ sided die having sides labelled with the elements of $\Omega$ until the last $n$ tosses agree with one player's word, and that player is declared the winner. For $n\geq 3$ the second player has a strategy which guarantees strictly better than even odds. Guibas and Odlyzko have shown that the last $n-1$ letters of the second player's optimal word agree with the initial $n-1$ letters of the first player's word. We offer a new proof of this result when $q \geq 3$ using correlation polynomial identities, and we complete the description of the second player's best strategy by characterizing the optimal leading letter. We also give a new proof of their conjecture that for $q=2$ this optimal strategy is unique, and we provide a generalization of this result to higher $q$.