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Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
Background: Aggressive surgical resections of posterior fossa tumours result in tremendous neurological sequelae as a result of damage to the brainstem. As such we sought to re-evaluate the role of aggressive surgical resections in the molecular era. Methods: 820 posterior fossa ependymoma and 787 medulloblastoma were genomically profiled and correlated with pertinent clinical variables. Results: Across 787 medulloblastoma cases, the value of extent of resection was greatly dampened when accounting for molecular subgroup. Near-total resections are equivalent to gross total resections across all four subgroups even when correcting for treatment. The prognostic value of a gross total resection as compared to a subtotal resection (>1.5cm2 residual) was restricted to Group 4 tumours (HR 1.26). Across 820 posterior fossa ependymoma PFA ependymoma was a very high risk group compared to PFB ependymoma, and a subtotal PFA ependymoma conferred an extremely poor prognosis. Gross totally resected PFB ependymoma could be cured with surgery alone. Prognostic nomograms in both medulloblastoma and ependymoma revealed molecular subgroup to be the most important predictor of outcome. Conclusions: The prognostic benefit of EOR for patients with medulloblastoma is marginal after accounting for molecular subgroup affiliation. In both molecular subgroups of posterior fossa ependymoma, gross total resection remains an important predictor of outcome.
Background: Inflicted head injury is a major cause of infant morbidity and mortality. The extent of traumatic brain injury in infants is often best characterized by diffusion weighted magnetic resonance imaging. In this cases series we describe four infants aged 6-19 months, with small unilateral subdural hematomas secondary to abusive head trauma accompanied by extensive areas of restricted diffusion weighted imaging isolated to the cerebral white matter. Methods: Retrospective, single-centre case series of four children with small unilateral subdural hematomas with early and delayed MR imaging with diffusion weighted imaging. Results: In three cases there was acute diffusion restriction ispilateral to the subdural, while in one case diffusion restriction was present bilaterally. All patients had multiple seizures and bilateral multilayered retinal hemorrhages. After non-surgical treatment, all patients survived albeit with significant motor and cognitive deficits and significant cortical atrophy on long-term followup imaging. Conclusions: These four cases highlight that relatively small subdural hematomas following child abuse can manifest with extensive white matter injury only evident at early stages with diffusion weighted imaging. We propose that selective white matter injury as a result of either reperfusion or axonal degeneration in response to the initial insult accounts for this novel pattern of infantile traumatic brain injury.
India's transition to an economy capable of high growth in the years since 1980 has been of global interest, discussion and research. The metaphor of an elephant to describe Indian economy muddling through gave way to that of a tiger unchanged in the 1990s. The Gross Domestic Product (GDP) per capita grew annually by an average of 1.2 per cent in the 1960s and 1970s but this growth rate changed to an average of 3.5 per cent in the 1980s, 3.7 per cent in the 1990s and 5.5 per cent in the 2000s. India has transformed itself to be counted among the fastest growing economies in the world with an average GDP per capita growth rate of 3.7 per cent in the years 1980 to 2004. In terms of GDP growth performance alone one finds that Indian economy's average annual growth rate was 3.5 per cent during 1951–82 (euphemistically called the Hindu Rate of Growth) that increased to 5.4 percent in the next two decades (1983–99) followed by a growth rate of above 7 per cent in the 2000s. The causes and outcomes of this economic transformation have been the subject of research and analysis in recent years. A perceptive analytical assessment of the evidence and factors driving change is available in Kotwal, Ramaswami and Wadhwa (2011). The economic policy reform of 1991 has played an important role in driving this growth but other pre-existing factors have also influenced the pattern of development (Kochhar, et al., 2006). First and perhaps the foremost feature of India's growth experience is that it is led by services sector unlike in other countries of East Asia and China. In the broader context of economic development and structural change, the observed sequence was that manufacturing followed agriculture while the service sector became prominent only at later stage. India's experience appeared to be different with the share of services sector in GDP sharply going up in the 1990s, beginning with a share of 43 per cent in 1990–91, to reach a high share of 57 per cent in 2009–10.
Productive employment opportunities constitute the primary ingredient of economic transformation and inclusive growth. This volume examines India's development experience in the sphere of labour, employment, structural change and institutional challenges in the recent past. The contributors have extended the boundaries of contemporary debate in a variety of ways by undertaking fairly detailed empirical analysis of selected aspects of growth and employment change in India. They uncover the recent patterns of change, between and within sectors over time that challenges popular beliefs and understanding of employment growth in India. Analysis of population ageing, gender discrimination, impact of labour regulation; institutional analysis; dynamics of judicial interpretation of laws protecting workers in the years of economic liberalisation among others have enriched the content. The volume contributes to our knowledge of India's labour market and sheds light on employment challenges in an economy undergoing rapid growth and economic transformation.
This volume presents an analysis of India's development experience in the sphere of labour, employment and economic growth in the recent past. Labour and employment issues have been central to India's growth and development debate in the 1980s through the 2000s. The economic policy debate in this area has been rather narrow, often confined to issues of jobless growth in the formal manufacturing sector, constraint of specific labour laws, informalization of employment relationships and information technology services sector growth. Authors in this volume have extended the boundaries of this debate in a variety of ways by undertaking a fairly detailed analysis of selected issues. Each author has approached the selected topic differently but consistent with the broad theme of the volume. They have used reliable data sets over time to uncover many quantitative dimensions of employment growth, structural change, population ageing, worker status (job quality), intensity of labour-use, gender discrimination and impact of labour laws and regulation. Some authors have pursued qualitative analysis like re-examining the legal definition of industrial worker through the lens of economic theory; how judiciary (Supreme Court of India) has interpreted labour laws and workers' protection in the years of economic liberalization. Their separate contributions read together I believe make a positive contribution to the existing empirical literature on growth and employment in India. The issues investigated are highly contemporary, live and are expected to challenge the evolution of economic policy in the immediate future.
I sincerely hope this volume will appeal to those in the area of academic research and as well as non-academic community of readers interested in the deep issue of growth and employment. Selected papers from this volume can be used as supplementary readings in any graduate course in Indian economy, development economics and policy and labour markets in developing countries.
Papers in this volume were first presented at a seminar held at Indira Gandhi Institute of Development Research (IGIDR) in Mumbai on 6–7 September 2013 on the occasion of Silver Jubilee Year of IGIDR.
India is well known for its extensive set of labour laws providing job security to regular industrial workers in the formal sector. Studying the response of firms to labour regulations constitutes a key component of one's understanding of the impact of labour laws on employment growth and access to good jobs in India. How have firms in India responded to Employment Protection Legislation (EPL) in terms of their hiring strategies, entry and size expansion decisions? Has EPL affected the upward mobility of firms? These are admittedly difficult empirical questions. In this chapter I provide preliminary econometric evidence that manufacturing firms in India employ non-permanent workers (contract workers) to avoid coming under EPL. Even in advanced country contexts, EPL and other related labour regulations are widely perceived to raise the expected cost of employment adjustment in firms covered by legislation, causing discontinuity in firm growth behaviour and employment policies. Labour regulations apply rules with respect to conditions of service, lay-off, retrenchment and closure to firms above a specified employment size. This is argued to raise labour adjustment costs and create pressures on firms to stay below the legal threshold size. Note that the regulations take effect as firm size grows and it generates an implicit tax. As the regulations are defined with reference to few finite employment size levels the literature refers to them as ‘threshold effects’ (see Gourio and Roys, 2012). The analytical idea of threshold effect is that if labour legislation (or any other economic policy like tax rates) changes discontinuously at the threshold employment size (or it could be asset size or output level) then it should result in discontinuous change in firms’ behaviour. This change in behaviour of firms is directly proportional to the costs of compliance above the threshold. The discontinuous regulation can have two effects. First it could influence the propensity of the firm to expand employment above the threshold size impacting firm size distribution.
3D integration enabled by through-silicon-via (TSV) allows continued performance enhancement and power reduction for semiconductor devices, even without further scaling. For TSV wafers with all Applied Materials unit processes, we evaluate the integrity of oxide liner and copper barrier by capacitance-voltage (C-V) and current-voltage (I-V) measurements, from which oxide capacitance, minimum TSV capacitance, and leakage current are extracted. The capacitance values match well with model predictions. The leakage data also demonstrate good wafer-scale uniformity. The liner and barrier quality are further verified with microanalysis techniques.
Oesophagitis dissecans superficialis is an extremely rare and benign condition where the mucosal epithelium of the oesophagus sloughs off along the whole length of the oesophagus and is expelled as an oesophageal cast. This condition has been reported in association with various aetiological factors. We report a case of an oesophageal cast in a patient who underwent repeated oesophagoscopy and dilatation for a postcricoid web. We discuss the possible relationship between trauma to the upper oesophagus and the development of oesophagitis dissecans superficialis.
V. Ramaswamy, Geophysical Fluid Dynamics Laboratory, Princeton Forrestal Campus 201, Princeton, NJ,
S. Ramachandran, Physical Research Laboratory, Ahmedabad, India,
Georgiy Stenchikov, Department of Environmental Sciences, Rutgers University, New Brunswick, NJ,
Alan Robock, Department of Environmental Sciences, Rutgers University, New Brunswick, NJ
As discussed in Chapters 1 and 4, radiation forcing from stratospheric aerosols contributes to the variability of the climatic system. This chapter provides a detailed analysis of how these aerosols affect Earth's climate system. Stratospheric aerosols, in the aftermath of intense volcanic eruptions, can perturb substantially the climate of the stratosphere and surface–troposphere system (IPCC, 1995). Typically, the particulates appearing initially are comprised of silicates (e.g., ash). These are large (diameter greater than a few microns) and tend to fall off rapidly (within a few months) (Robock et al., 1995). The conversion of the sulfur-containing gases injected into the stratosphere to sulfate aerosols occurs in a few weeks to months. This results in a loading of the stratosphere with submicron sulfate aerosols having a residence time of one to two years. The radiative effects depend on the type, size, and shape of the particulates. While in the first several weeks, the radiative effects may be dominated by the ash particles, over the longer term (after a few months and up to ∼ two years) and of considerable relevance to climate, the sulfate aerosols dominate the effects. We focus on the effects due to sulfate aerosols in this study.
Sulfate aerosols possess absorption bands in both the solar and longwave spectra, and have significant scattering ability in the solar spectrum.