The aim of this thesis is to examine the decline in fertility rate in post-war Italy and identify its causes. Fertility rate in Italy dropped dramatically across 1970-2010 in a stark departure from the nation's previous reproductive patterns. This has led to an increasingly aging population, and holds important implications for Italy's future.
This study demonstrates that there has been a meaningful shift in cultural values that has led to fertility decline in Italy since 1970. In order to provide historical context for the importance of this cultural shift, the thesis first presents the Italian culture and familial structure of the twentieth century. Scholarly writings, fascist policies, and Church teachings are used to demonstrate the traditional family ideology and pro-natalist attitudes that permeated Italian culture in the first half of the twentieth century.
Following this, the thesis delves into a more comprehensive study of the 1960s and 1970s, the decades that mark the beginning of fertility decline in Italy. It thus examines the Italian women's movement and the changes it spearheaded. Feminist texts, changes in legislation, and popular survey data are employed to reveal shifting values taking place during this time period. This evidence illuminates Italian women's changing attitudes towards family and gender relations and indicates that the 1960s and 1970s witnessed the creation of new cultural values that would in turn influence Italian women's choices across the next four decades.
The thesis then provides an analysis of three factors in contemporary Italian society and their relationship to fertility rate. An investigation of Italian women's new attitudes and behaviors in the realms of labor force participation, marriage, and division of unpaid labor help to demonstrate the underlying causes of fertility decline: devaluation of the traditional family structure. An exploration of continued structural barriers for women in these areas demonstrates the ideological mismatch that has pushed Italian women into an either/or relationship between a traditional family and personal autonomy. Therefore, changing patterns in these realms are shown to spring from the same cause that this thesis postulates has led to fertility decline in Italy: a meaningful shift in cultural values.


This purpose of this article is to explore differences by gender and school grade in patterns of association among social influences and tobacco use. Data from the 1999 (N = 15,038) and 2000 (N = 35,828) National Youth Tobacco Survey (American Legacy Foundation, 1999, 2000), a nationally representative, repeated cross-sectional survey, were used in the analysis. The authors compared effects on adolescent smoking. Direct paths from social environment to current smoking increased from middle school to high school. Indirect paths with social image mediating this relationship revealed a smaller increase. The pattern was constant across subsamples. Social image of smokers mediated the influence of social environment on adolescent smoking. Social image had a greater effect on smoking among middle school boys and high school girls.


BACKGROUND
Although autogenous bone is the most widely used graft material for spinal fusion, demineralized bone matrix preparations are available as alternatives or supplements to autograft. They are prepared by acid extraction of most of the mineralized component, with retention of the collagen and noncollagenous proteins, including growth factors. Differences in allograft processing methods among suppliers might yield products with different osteoinductive activities. The purpose of this study was to compare the efficacy of three different commercially available demineralized bone matrix products for inducing spinal fusion in an athymic rat model.

METHODS
Sixty male athymic rats underwent spinal fusion and were divided into three groups of eighteen animals each. Group I received Grafton Putty; Group II, DBX Putty; and Group III, AlloMatrix Injectable Putty. A control group of six animals (Group IV) underwent decortication alone. Six animals from each of the three experimental groups were killed at each of three intervals (two, four, and eight weeks), and the six animals from the control group were killed at eight weeks. At each of the time-points, radiographic and histologic analysis and manual testing of the explanted spines were performed.

RESULTS
The spines in Group I demonstrated higher rates of radiographically evident fusion at eight weeks than did the spines in Group III or Group IV (p < 0.05). Manual testing of the spines at four weeks revealed variable fusion rates (five of six in Group I, two of six in Group II, and none of six in Group III). At eight weeks, all six spines in Group I, three of the six in Group II, and no spine in Group III or IV had fused. Histologic analysis of the spines in Groups I, II, and III demonstrated varying amounts of residual demineralized bone matrix and new bone formation. Group-I spines demonstrated the most new bone formation.

CONCLUSIONS
This study demonstrated differences in the osteoinductive potentials of commercially available demineralized bone matrices in this animal model.


Discipline is an important aspect of the life of any school. Learning and teaching can only take place effectively in a disciplined environment. In South Africa, discipline policies might not have been effectively implemented due to inadequate sources, lack of commitment and training of school leaders. A qualitative research design was utilized for the investigation on which this article is based. The research consisted of two phases. First, group interviews were conducted with 27 B Ed Honours students; thereafter, individual interviews were conducted with a total of six students selected by purposive sampling. The results seem to suggest that the broader school community should be taken on board to ensure effective discipline policy implementation. The correct legal sources should furthermore be employed in the process of developing school policies. School leaders need thorough training for the development and implementation of discipline policies. Several measures are suggested for the effective introduction of disciplinary policies, among others, that school leadership should play a (more) active role; specifically the principals of schools should be willing to share their knowledge on the implementation of school disciplinary policies with other members of the school leadership.


Introduction: Gefitinib, an orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces growth arrest in squamous cancer cell carcinoma of head and neck (SCCHN) cell lines mainly by blocking cells in G1 and preventing them from entering the cell cycle. Clinical studies have demonstrated the activity of gefitinib monotherapy in SCCHN. Preclinical studies have shown that the combination of radiotherapy (RT) and drugs interfering with the EGF pathway may result in radiosensitization in squamous cell carcinomas that over express EGFR.
Purpose: Two different doses of gefitinib, administered along with standard radiation therapy, were tested in locally advanced inoperable head and neck cancer who have neiver received radiotherapy or chemotherapy or undergone surgery for head and neck carcinoma, with the aim of finding the maximum tolerated dose and assessing the toxicity and activity of the combination.
Patients and methods: The standard "3+3" design was used for the phase I study. Radiation therapy was given according to conventional dose and schedule. Gefitinib dose escalation was stopped if more than a third of patients of a given cohort had dose limiting toxicity (DLT).
Results: DLT was observed in 3 out of 4 patients treated at the dose of 500 mg and included grade 3 stomatitis in 3 patients and grade 3 liver toxicities in 1 patient. The dose level of 250 mg was recommended for the phase II study. Six confirmed objective responses were observed among 16 patients. Four patients had a complete response, which was confirmed in three cases; eight patients had a partial response, which was not confirmed in six patients. Stable disease and disease progression were observed in one and three patients, respectively. Median duration of response was 5.4 (range: 1–21) months. The observed stable disease lasted 7.4 months. The median progression free-survival was 6.7 months (95% CI: 4.5–12.1) and the median OS was 8.5 months.
Conclusion: Our results do not support further trials with gefitinib and radiation therapy, according to our schedule, in this patient population. Integration of gefitinib within chemoradiotherapy regimens and combination with other biological therapies may represent the next challenge.


Depending on the goal of an instance of the Knowledge Discovery in Databases (KDD) process, there are instances that require more than a single data mining algorithm to determine a solution. Sequences of data mining algorithms offer room for improvement that are yet unexploited. If it is known that an algorithm is the first of a sequence of algorithms and there will be future runs of other algorithms, the first algorithm can determine intermediate results that the succeeding algorithms need. The anteceding algorithm can also determine helpful statistics for succeeding algorithms. As the anteceding algorithm has to scan the data anyway, computing intermediate results happens as a by-product of computing the anteceding algorithm's result. On the one hand, a succeeding algorithm can save time because several steps of that algorithm have already been pre-computed. On the other hand, additional information about the analysed data can improve the quality of results such as the accuracy of classification, as demonstrated in experiments with synthetical and real data.


Introduction: Emergent technologies, i.e., monopolar capacitive coupled
Radiofrequency (mcRF) and Platelet Rich Plasma (PRP) are now available to
treat conditions characterized by a failed Wound Healing Response. Both mcRF
and PRP positively influence the chemical/cellular inflammatory cascade to promote
healing. mcRF application results in temperature elevation at the targeted
structure up to 50℃ stimulating heat shock proteins, thus inciting the Wound
Healing Response. Ultrasound-guided PRP injections results in an inflammatory/reparative reaction through cytokinin
release. Methods: Sixty-eight patients who have failed previous conservative
treatment for tendinopathies and chronic ligament conditions of the elbow,
hip, knee and ankle/foot, were treated either with mcRF or PRP. Treatments
were delivered directly by the investigator, and patients were followed
prospectively for an average of 19.7 months (range 15 to 24 months). Results: Average
age for the mcRF cohort was 53 years (range 17 to 88). Average age for the PRP
group was 58 (range 19 to 90). The male to female ratio for both groups was
1/1. 33 of 42 patients treated with mcRF experienced marked improvement (78%),
while in the PRP group 19 of 26 patients experienced marked improvement (73%)
as self-assessed by study subjects. Discussion/Conclusion: Results of this
study are in agreement with reports on the use of both technologies; however, this is the first time that a
side-by-side comparison is established. PRP and mcRF represent a new approach
to musculoskeletal pathology; both modalities aim at inducing a biological
response and are considered at the frontier of regenerative therapeutics.
The high safety profile suggests that these, non-invasive (mcRF) and minimally invasive
(PRP), office-based alternatives for the management of musculoskeletal
conditions are valuable tools and should be used in accordance with a clear
understanding of the underlying pathology.


Primitive Neuro Ectodermal Tumours' (PNET) are highly aggressive embryonal tumours of presumed neural crest origin. They are derived from neoplastic transformation of common progenitor cells in the sub ependymal matrix layer. They are more common in children. They are small round cell tumours affecting the central nervous system (CNS), others being Ewing's sarcoma, medullobalstoma, lymphomas etc. They are classified based on their immune histochemical characteristics- neuronal, astrocytic, ependymal, retinal photo receptor, undifferentiated. Undifferentiated variety carries better prognosis. GFAP expression is an important prognostic factor. Presence of p53 germ line mutation indicates an increased risk for developing PNET. Spinal PNET are secondary to CSF metastasis from cranium commonly. Primary spinal PNET tumours are rare and extradural location is extremely rare. PNET needs multimodality approach but carries poor prognosis when compared to other CNS tumours.


This is a study of architectural competitions as they engage with the design practices of architects within the UK and Europe. Since only one firm or one design emerges at the end, and the project programme exists prior to the submissions, there tends to be a gap between programme and practice, past and future, language and situation. It is the aim of this research to investigate what changes in our understanding of architectural practice when we acknowledge that architects work to linear programmes and submit deliverables within the set of relations that make up the competition. In conducting this research I address a gap in the social scientific understanding of architectural practice. While ethnographies of architectural studios have described the way design emerges through an interplay of humans and nonhumans, formats or structures like the competition have not yet become analytical categories in the ethnographic literature. To bridge what seems like a gap between the immaterial world of the competition and the material world of the studio, I draw from actor-network theory to view the competition as a set of relations that include objects and practices. Considering the technology of the competition, I follow five different strands of research. I identify the matters of concern that architects talk about when they talk about competitions; examine the documents involved in administering a competition; follow an atelier at an architectural school where students participate regularly in competitions; observe the Office of Metropolitan Architecture prepare a concept design; and visit an exhibition of submissions. Here I describe the ways in which competitions come together within the practice of architects. This study makes three contributions. First, the study adds to our understanding of architecture as a set of relations, rather than a stable identity. The second contribution has to do with language and practice, demonstrating that ?big? categories like ?building? nevertheless act within collectives of architects, clients, contractors and so on. A final implication is for methods. Since certain categories exist between sites, organising the activity of actors in different offices across what might be hundreds of miles, ethnographic fieldwork on architecture can become fragmented and multi-sited. The implications of the architectural competition for an ethnographic understanding of architectural practice, then, are to see more and ?bigger? collectives within the lives of architects.


Attribution is the process by which individuals explain the causes of behavior and events. Harold Kelley's Co-variation Model of Attribution is one of the widely discussed and credited for being thorough and useful. The model states that attribution process involves deciding whether an observed behavior is internally or externally caused and that determination largely depends on three factors: Distinctiveness, Consensus and Consistency. This study tested the Kelley's model by analyzing employees' attribution about performance of other employees. Sample consists of 92 teachers working in the various campuses at the University of Sindh. Close-ended questionnaire comprising 36 items was used for data collection. Respondents were asked about the causes—internal or external—of other employees' performance. Three task behaviors (teaching subjects, evaluating students, and class control) and three contextual behaviors (treating students, relation with colleagues, defiance) were taken for assessing attribution. The data were analyzed using SPSS in terms of Mean, Mode, Median, Inter quartile range, one sample t -test and Chi Square. Hence, findings relatively supported the model. Low distinctiveness, High consensus and High consistency cause people to attribute in the way as described by Kelley, whereas High distinctiveness and Low consistency were very slightly attributed to external factor and Low consensus was slightly attributed to internal factors. ‗High distinctiveness is cause of external attribution' got the least support, whereas ‗high consistency is cause of internal attribution' got highest support. Managers and employees should adapt or maintain their behavior keeping in view the attribution of employees for improving organizational effectiveness. Though model was not strongly supported, that proves that it is not a rule of thumb and seeks identification and development of new and other theories/models.


Abstract. The potential impact of climate change on agriculture is uncertain. In addition, agriculture could influence above- and below-ground carbon storage. Development of models that represent agriculture is necessary to address these impacts. We have developed an approach to integrate agriculture representations for three crop types – maize, soybean, and spring wheat – into the coupled carbon–nitrogen version of the Community Land Model (CLM), to help address these questions. Here we present the new model, CLM-Crop, validated against observations from two AmeriFlux sites in the United States, planted with maize and soybean. Seasonal carbon fluxes compared well with field measurements for soybean, but not as well for maize. CLM-Crop yields were comparable with observations in countries such as the United States, Argentina, and China, although the generality of the crop model and its lack of technology and irrigation made direct comparison difficult. CLM-Crop was compared against the standard CLM3.5, which simulates crops as grass. The comparison showed improvement in gross primary productivity in regions where crops are the dominant vegetation cover. Crop yields and productivity were negatively correlated with temperature and positively correlated with precipitation, in agreement with other modeling studies. In case studies with the new crop model looking at impacts of residue management and planting date on crop yield, we found that increased residue returned to the litter pool increased crop yield, while reduced residue returns resulted in yield decreases. Using climate controls to signal planting date caused different responses in different crops. Maize and soybean had opposite reactions: when low temperature threshold resulted in early planting, maize responded with a loss of yield, but soybean yields increased. Our improvements in CLM demonstrate a new capability in the model – simulating agriculture in a realistic way, complete with fertilizer and residue management practices. Results are encouraging, with improved representation of human influences on the land surface and the potentially resulting climate impacts.


Environmental Liability in the EU focuses on the 2004 EU Environmental Liability Directive - one of the most significant pieces of environmental legislation of the last ten years. The book provides an overview and introduction to the scheme of the Directive and discusses various specific aspects such as its measure of damages, its rules regarding the liability for damage caused by genetically modified organisms and soil pollution, the issue of standing and its relationship with international civil liability conventions that cover environmental harm, in particular the ones dealing with oil pollution. GMO damage is likewise examined against the backdrop of developments at the global level, i.e. the emerging liability regime under the Cartagena Protocol.Environmental Liability in the EU also addresses the issue of who can be held liable for damage covered by the Directive (operator liability), the available defences and its relation to the general principles of EC Environmental Law, notably the polluter-pays principle and the precautionary principle. Given the fact that the Directive is partly based on US and Member State law, a comparison is made with relevant US federal laws, namely the US Oil Pollution Act and CERCLA, as well as with the law of some Member States (Germany and the United Kingdom). A scientific paper considers - by way of case study - complex questions of proof of causation of (environmental) damage caused by arsenic.


On May 17, 1954, the United States Supreme Court handed down its historic decision in Brown v. Board of Education, (1) and almost immediately officials of the National Association for the Advancement of Colored People met in Atlanta, Georgia, to celebrate and to confer. On May 23 and 24, they met to plan for a future filled with hope. With the firm belief that their goals could be realized in the wake of Brown, they issued a statement that has come to be known as the "Atlanta Declaration." (2) Over time, this document has been obscured, to an extent that few students of civil rights are familiar with it. But this declaration is, in fact, the most authentic and definitive commentary on the hopes of black Americans following Brown. The NAACP, with other individuals, developed a strategy and embarked on a mission to eradicate the pernicious separate-but-equal doctrine that had been enunciated as the law of the land in Plessy v. Ferguson, (3) a decision in which the Court ignominiously betrayed the hopes of black Americans. No commemoration of Brown can be credible, nor can the decision be evaluated effectively at this point in history, without revisiting and understanding the Atlanta Declaration. The full text of the declaration reads: We, as representatives of the National Association for the Advancement of Colored People from seventeen Southern and Border States and the District of Columbia, have assembled here in Atlanta, Georgia, May 22-23, for the purpose of collectively developing a program to meet the vital and urgent issues arising out of the historic United States Supreme Court decision of May 17 banning segregation in public schools. All Americans are now relieved to have the law of the land declare in the clearest language: "... in the field of public education the doctrine of 'separate but equal' has no place. Separate educational facilities are inherently unequal." Segregation in public education is now not only unlawful: it is un-American. True Americans are grateful for this decision. Now that the law is made clear, we look to the future. Having canvassed the situation in each of our States, we approach the future with the utmost confidence. This confidence is based upon the many factors including the pledges of support and compliance by governors, attorney generals, mayors, and education officials; and by enlightened guidance of newspapers, radio, television and other organs of public communication and comment. We stand ready to work with other law-abiding citizens who are anxious to translate this decision into a program of action to eradicate racial segregation in public education as speedily as possible. We are instructing all of our branches in every affected area to petition their local school boards to abolish segregation without delay and to assist these agencies in working out ways and means of implementing the Court's ruling. The total resources of the NAACP will be made available to facilitate this great project of ending the artificial separation of America's children on the irrelevant basis of race and color. While we recognize that school officials will have certain administrative problems in transferring from a segregated to a non-segregated system, we will resist the use of any tactics contrived for the sole purpose of delaying desegregation. In pursuit of our objectives, we will accelerate our community action program to win public acceptance of the Court's desegregation order from all segments of the population. To this end, we are confident of the support of teachers, parents, labor, church, civic, fraternal, social, business and professional organizations. We insist that there should be integration at all levels including the assignment of teacher-personnel on a non-discriminatory basis. …


Introduction

Contemporary health systems are deeply complex, organisationally and temporally. Recently, focus has increasingly been given to patient experiences and needs (LaVela & Gallan, 2014) and to developing services that accommodate a diversity of needs within formal institutions and their extensions into society. With patient-centred recovery and well-being as a focus, the challenge arises as to how innovative and sustainable services can be developed in contexts of such systems. While Service Design (SD) has emerged as a domain of design-based inquiry and professional practice, early studies have often centred on commercial partners, service delivery, customer experience and satisfaction views. However, such approaches ought to be coupled with Systemic Design efforts, due to the socio-technological complexity and interlinked nature of healthcare service development and change management (Jones, 2013). This is crucial in the front-end of related design.

In the Nordic countries, the public healthcare sector is seeking to increase partnerships with private actors in order to reach policy goals and offer healthcare services to a wider demographic in a time of resource shortage. Ensuring a fruitful collaboration between public and private sectors becomes central as a matter of design and innovation. Such collaborations also amount to complex social systems, where actors need to understand patient journeys and medical procedures, co-create innovative solutions and distribute ownership, assignments and risks. Establishing collaborative partnerships between healthcare actors and private commercial actors can be challenging due to the deeply institutionalised ways of working and siloed expertise of the medical sector.

This calls for processes and tools that support communication and alignment of diverse actors' views embedded in such complex social systems to be further developed and better understood systemically. This is especially crucial in the front end of related design, often referred to as the 'fuzzy front end'. The authors have tackled these challenges facing innovative partnerships through the development and proposal of a Strategy Sandbox workshop pilot.

Developing a Strategy Sandbox for healthcare service innovation

Innovation processes are often divided in three areas: the fuzzy-front end (FFE), new product development (NPD) and commercialisation (Koen et al., 2002). The FFE determines what is to be developed on a conceptual level, but does not develop the details for a specific solution, hence the term 'fuzzy'. In healthcare cross-sector collaborations, all actors need to gain an understanding of patient journeys and medical procedures early on, to be able to co-create innovative concepts and make a planning for the distribution of ownership, assignments and risks. This paper therefore proposes the introduction of a preliminary phase of the FFE, termed the 'pre-fuzzy front end' (PFFE), supporting an alignment of relationships between participating actors and the co-creation of a shared understanding of the object of development before entering the FFE.
Through defining the PFFE, the authors have questioned:How may service design support multiple actors (public and private) in aligning their expectations, needs and goals to co-envision new directions for patient-centric healthcare service innovation in the pre-fuzzy front end of a development process?
Rooted in qualitative inquiry and practice based research, the authors have made use of a blend of methods to approach this question: research by design, reflection on action and analysis of data such as sketches photographs and contextually designed facilitation tools that unpack the fuzzy front end site in wider reflexive and iterative innovation processes.

Understanding the complexity of service-system relations

The sandbox metaphor is borrowed from innovation processes and product R&D and is perceived as a conceptual workspace encouraging exploration, experimentation and interaction between diverse actors. It is informed by the Centre for Connected Care (C3) research investigating innovation labs (Carstensen & Bason, 2012) and co-design communication tools (Sanders & Stappers, 2008) that are used within the context of healthcare service design. The research draws parallels to design oriented innovation venues in health, e.g. the 100-days challenge of Nesta Health lab (UK), Experio lab (Sweden) and Mindlab (Denmark).

One of the features of complex systems is layering, meaning that different phenomena and unpredictable qualities can appear at different levels of aggregation and spatial scale (Liljenstrom & Svedin, 2005). The Strategy Sandbox has therefore set out to unpack the complexity of healthcare service development on three levels: Macro (mapping stakeholders needs), micro (mapping user needs and experiences) and meso (co-envisioning and co-developing possibility areas). Sandboxes have also been described as having four key features: connectors, framing, space and speed (Clarke, 2017). The workshops explored early phase formation of innovative partnerships within the C3 stroke project. With 47 participants in total, the concept has been run as an innovation partnership and public procurement between public sector actors and commercial vendors to innovate products and services to address unmet needs.

Workshop 1

Working on a macro level, the first workshop aimed at aligning the participating actors by creating a shared overview of their needs and perspectives, allowing them to express their opinions and views. Tailored communication tools mediated discussions between workshop participants, facilitating the sharing of perspectives on the service situation and proposals of possible public private partnerships. (Figure 1).

Actor needs were filtered via criteria derived from medical health professionals, designers and participants where a visual relational mapping clarified available resources in the actor network. By using physical tools, concepts were re-evaluated and adapted leading to concept shifts (Buur, 2012) where a proposal was presented regarding what a med-tech company might offer in developing innovative purchases following defined needs. This, we see as a systems oriented design mode of exploring service networks.

Workshop 2

On a micro level, the second workshop facilitated a detailed mapping of users' needs and experiences and an exploration of different public-private partnerships. Here, we sought to unpack systemic complexity in two ways: 1) mapping patient needs and experiences, and 2) exploring partnership possibilities for technology, users and health service professionals. The workshop made apparent patient views through their participative engagement in patient journey experience mapping, specifically in transitional parts of the service trajectory.
Between workshops, project team meetings were held to reflect on and analyse the previously generated data, leading to plans and strategies for the next workshop. Ten possible areas of development were identified and used as a basis for workshop number three.

Workshop 3

The third workshop of the Strategy Sandbox was dedicated to co-assessment and co-development of the identified possibility areas on a meso level. Evaluations of previous mappings and explorations to develop ten possibility areas for new systemically situated service development, were evaluated and revised to: 1) strengthen patient cognitive assessment, 2) secure further and consistent treatment practices, 3) empower the patient, family and carer givers, and 4) implement distance monitoring and digital touchpoints. To facilitate the evaluation and selection of focus areas for the wider project, a holistically oriented health technology co-assessment tool was developed by the authors (Figure 2).

Future pathways

Through utilising a service systems design process and taking a 'pre-fuzzy front end' approach to strategy sandboxes, the stroke project managed to leverage proposals of strategies for matching the aims of technology partners with the service directions of the public healthcare actors. The workshop process facilitated an alignment of expectations and goals amongst participating actors, an identification of needs both for participating actors and end users, and co-envisioned directions for service innovation within the topic of stroke.
Service systems relations are layered and entangled and take time to be understood by a wide network of diverse actors. Our inquiry this far indicates that in order to accommodate the time needed to develop an understanding of the complex relations involved in healthcare collaborations, there is a need for a pre-fuzzy front end alignment phase within service innovation processes. Furthermore, to support the development of more sustainable and accessible healthcare services, this pre-fuzzy front end phase can greatly benefit from more systems oriented design approaches being incorporated into strategic workshop facilitation design.


Background: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. Methodology: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO). UCO animals were randomized to saline (n = 11), therapeutic hypothermia (TH; n = 6), or TH + erythropoietin (Epo; n = 8). Epo was given on days 1, 2, 3, and 7. Animals had serial developmental assessments and underwent magnetic resonance imaging with diffusion tensor imaging at 9 months of age followed by necropsy. Histology and immunohistochemical (IHC) staining of brain and brainstem sections were performed. Results: All UCO animals demonstrated and met the standard diagnostic criteria for human neonates with moderate-to-severe HIE. Four animals developed moderate-to-severe CP (3 UCO and 1 UCO + TH), 9 had mild CP (2 UCO, 3 UCO + TH, 3 UCO + TH + Epo, and 1 control), and 2 UCO animals died. None of the animals treated with TH + Epo died, had moderate-to-severe CP, or demonstrated signs of long-term neuropathological toxicity. Compared to animals grouped together as having no CP (no-CP; controls and mild CP only), animals with CP (moderate and severe) demonstrated decreased fractional anisotropy of multiple white-matter tracts including the corpus callosum and internal capsule, when using Tract-Based Spatial Statistics (TBSS). Animals with CP had decreased staining for cortical neurons and increased brainstem glial scarring compared to animals without CP. The cerebellar cell density of the internal granular layer and white matter was decreased in CP animals compared to that in control animals without CP. Conclusions/Significance: In this nonhuman primate HIE model, animals treated with TH + Epo had less brain pathology noted on TBSS and IHC staining, which supports the long-term safety of TH + Epo in the setting of HIE. Animals that developed CP showed white-matter changes noted on TBSS, subtle histopathological changes in both the white and gray matter, and brainstem injury that correlated with CP severity. This HIE model may lend itself to further study of the relationship between brainstem injury and CP.


On February 20, 2013, the Supreme Court announced its decision in Gunn v. Minton. There the Court revisited the scope of statutory "arising under" jurisdiction in the context of a legal malpractice suit premised on alleged attorney errors committed in a prior patent litigation. The significance of the decision transcends the specific context in which it arose. Although Gunn involved patent law arising under jurisdiction, 28 U.S.C. §1338, that jurisdictional standard is interpreted in precisely the same manner as the identically worded §1331 standard. Hence, the decision in Gunn applies to a full range of federal question cases in which a federal issue is embedded in a state-law claim. In addition, Gunn provides insight into the ongoing clash between principle and docket-management concerns that has become so characteristic of Supreme Court decisions in the realm of procedure.The Gunn opinion was much anticipated by the legal community since prior decisions by the Court had generated considerable confusion as to the scope of arising under jurisdiction in so-called "federal-ingredient" cases. Some commentators hoped that the Court would adopt the creation test as the exclusive measure of jurisdiction. Others hoped for a clarification of the federal-ingredient test. Still others, like this author, hoped that the Court would redirect the jurisdictional analysis to the traditional fundamental principles that once animated federal question jurisdiction. As I explain in my article, everyone will be disappointed by the result. The specific jurisdictional issue in Gunn focused on what had come to be known as the third and fourth prongs of the "Grable test," namely, whether the federal ingredient embedded in the plaintiff's state-law claim was substantial and whether the exercise of jurisdiction over that claim would upset the congressionally mandated balance between federal and state courts. Lower courts had been struggling with the interpretation and application of both prongs. Some had adopted detailed and highly technical doctrinal tests that led to counterintuitive results where jurisdiction was denied over concededly "significant" federal questions. Others had adopted a more holistic approach, seemingly designed to apply Grable test and, at the same time, avoid that test's obvious strictures.Some lower courts actually confessed that the jurisdictional determination was subjective and speculative and that, under similar circumstances, different judges might reach different conclusions. While the Gunn Court did address both Grable prongs, it did little other than endorse its previous iterations of those elements, providing neither a defense for them nor a principled method through which they might be applied. Thus, much of the confusion over federal jurisdictional standards that preceded Gunn remains largely unresolved.In this article, I begin by assessing the development of statutory arising under jurisdiction from its nineteenth century roots to the Court's most recent decisions. Here I examine the fundamental-principles compass that was developed by the Court in foundational arising-under cases, and synthesized succinctly by Justice Cardozo in Gully v. First Nat. Bank in Meridian. There the Court endorsed a unified jurisdictional theory that focused on the role of the federal issue in the case, asking whether the case was truly about federal law, for if the case was truly about federal law, the exercise of jurisdiction would be inherently consistent with congressional intent to provide a forum for federal question cases.With this fundamental-principles model as my foundation, I then examine more recent arising-under cases and show that, beginning in the 1980s, the compass got lost and was replaced by a maze of increasingly complex doctrinal tests disconnected from logical and well-established jurisdictional principles. Here the focus shifted from the federal nature of the controversy to a policy-driven model weighted heavily toward case-management concerns.Gunn offered the Supreme Court an opportunity to recapture the compass or, at the very least, to provide a comprehensible map that would assist lower federal courts in navigating the judicially created maze. The Court, however, missed that opportunity. Instead, the Court continued along a meandering doctrinal path that diverges from the fundamental principles of jurisdiction and often leads to results inconsistent with the congressionally mandated goal of providing a federal forum for the interpretation and application of the principles of federal law.


Bubble behaviour and absorption rate of gas injected into a liquid bath through rotary L-shaped lances were studied by cold models. A high-speed video recording system was used to measure the bubble diameter and the rising velocity. The absorption rate of injected CO2 gas in aqueous NaOH solution was measured by using a pH meter. It is found that the lance rotation leads to a decrease in the bubble diameter and the rising velocity as compared with the stationary lance. The bubbles produced by a multi-hole lance are smaller than those produced by a single-hole lance. The reduction in the bubble rising velocity is connected with the decrease in the bubble diameter, distribution of bubbles over the liquid bath and distortion of the bubble rising path due to the lance rotation. The gas absorption rate for the rotary lances is larger than that for the stationary lance. The effect of the rotation speed on volumetric mass transfer coefficient is larger at lower gas flow rate. The multi-hole lance can increase the volumetric mass transfer coefficient by about three times larger than the single-hole lance.The results are discussed in terms of the bubble coalescence, mass transfer coefficient and total interfacial area between bubbles and liquid


This article examines the ameliorative options facing people with hearing loss in mid-nineteenth-century Britain. As reflected in professional journals of the day, medical understanding of diseases and dysfunctions of the ear was limited, yet there was vigorous assertion and counter-claim as to the cause and treatment of problems. At the time, medicine was largely unregulated and quack practitioners were also able to promote their nostrums and services to a credulous the general public with little chance of a genuine cure for their hearing loss. Using the nineteenth-century British Library Newspapers Archive for 1850, 379 advertisements offering cures for deafness were identified and examined to illustrate the variety of nostrums and devices offered to the public. Individuals with hearing loss were easy prey when even qualified medical practitioners had little understanding of cause or treatment, and when scant legal protection protected them from fraudulent treatment claims or offered redress for their failure.


Wherever humans go they found calamities, diseases and deaths. People were buried under sand, mud, mountains, etc., they (scientists) found skeletons after excavation. What was/were the cause/causes? Some said that it is due to plague, or some kind of epidemics, malaria, cancer, etc.; but nobody knows what is/are the exact cause or causes. If we find the causes we can prevent or treat people with some plants or minerals as medicines. Question is what type of medicine? How to know that a certain plant or mineral will cure or is poison to man? How to give them? Was there any method, rule or Law? No. Let us take the history of medicine. Actually nobody knows the history. Let us take first century. During olden days for various diseases, plants, leaves, juices, barks, minerals, etc; were used singly or in mixtures of many so called medicines/drugs and experiments were done on patients. There was no method, rule or law. All was in chaos and thousands were disfigured, suffered, poisoned, burned, dead and buried. Now let us take from 15th. Century and forget the past. Should we?


We propose a new repeat-until-success (RUS) measurement-based scheme to implement quantum controlled phase gates according to the effect of dipole-induced-transparency (DIT) in a cavity and single-photon interference at a 50:50 beam-splitter. In our scheme, the DIT effect can appropriately attach a photon to the state of the dipoles according to their initial state, and in this way, a suitably encoded dipole-photon state is thus prepared. The measurement of the photon after it passing through a 50:50 beam-splitter can project the encoded matter-photon state to either a desired phase gate operation for the matter qubits or to their initial states. The recurrence of the initial state permits us to implement the desired entangling gate in a RUS way.


Summary: Protein–protein interaction detection methods are applied on a daily basis by molecular biologists worldwide. After generating a set of potential interactions, biologists face the problem of highlighting the ones that are novel and collecting evidence with respect to literature and annotation. This task can be as tedious as searching for every predicted interaction in several interaction data repositories, or manually screening the scientific literature. To facilitate the task of evidence mining and novelty assessment of protein–protein interactions, we have developed a Cytoscape plugin that automatically mines publication references, database references, interaction detection method descriptions and pathway annotation for a user-supplied network of interactions. The basis for the annotation is ConsensusPathDB—a meta-database that integrates numerous protein–protein, signaling, metabolic and gene regulatory interaction repositories for currently three species: Homo sapiens, Saccharomyces cerevisiae and Mus musculus. Availability: The ConsensusPathDB plugin for Cytoscape (version 2.7.0 or later) can be installed within Cytoscape on a major operating system (Windows, Mac OS, Unix/Linux) with Sun Java 1.5 or later installed through Cytoscape's Plugin manager (category 'Network and Attribute I/O'). The plugin is freely available for download on the ConsensusPathDB web site (http://cpdb.molgen.mpg.de). Supplementary information: Supplementary data are available at Bioinformatics online. Contact: email@example.com


This chapter seeks to determine to what extent there is cross-linguistic evidence for postulating clusters of predicate-specific semantic roles such as experiencer, cognizer, possessor, etc. For this, we survey non-default case assignments in a sample of 141 languages and annotate the associated predicates for cross-linguistically recurrent semantic roles, such as 'the one who feels cold', 'the one who eats sth.', 'the thing that is being eaten'. We then determine to what extent these roles are treated alike across languages, i.e. repeatedly grouped together under the same non-default case marker or under the same specific alternation with a non-default marker. Applying fuzzy cluster and NeighborNet algorithms to these data reveals cross-linguistic evidence for role clusters around experiencers, undergoers of body processes, and cognizers/perceivers in one- and two-place predicates; and around sources and transmitted speech in three-place predicates. No support emerges from non-default case assignment for any other role clusters that are traditionally assumed (e.g. for any distinctions among objects of two-argument predicates, or for distinctions between themes and instruments).


Seismic reflection profiling across exposed upper and middle crustal rocks of the Ruby-East Humboldt metamorphic core complex delineates important characteristics of the crustal structure developed during Tertiary extensional deformation. The goals of this study were to trace a Tertiary extensional shear zone from mylonitic surface outcrops into a seismic section and to characterize the deeper crustal fabric associated with the polyphase deformational history of the complex. Reflections in the shallow surface correlate with a plastic to brittle shear zone that formed during the tectonic unroofing of the middle crustal rocks. Constructive interference from strong planar layering in the mylonitic shear zone is considered chiefly responsible for generating the reflections. East and southwest dipping reflectors in the seismic section appear to correlate with exposed, opposing dipping mylonitic foliation domains. The opposing dips of the mylonitic layering may reflect warping of the normal-sense shear zone during tectonic exhumation coupled with an overall anastomosing character. Deeper in the section, a heterogeneous reflection character correlates with increases in velocity shown from wide-angle measurements in this region and is interpreted as penetrative fabric originating from extensional flow facilitated by broad-scale pure shear and localized simple shear. Lower crustal rocks apparently achieved granulite facies metamorphism during extension. A maximum of 6–8 km of mafic material could have been added to the crust during Cenozoic extension. The Moho reflection has such a high amplitude that it may be caused by partially molten rocks interleaved with peridotite. Reflections from the Moho show no significant upwarping of the base of the crust beneath the core complex. This suggests that the lower-crustal configuration is at least as young as the period of extensional activity that lasted from approximately 40 to 20 Ma which was responsible for the exhumation of the metamorphic core complex.


BACKGROUND
The past several years have seen the approval of five different biologic agents for the treatment of moderate to severe plaque psoriasis in the United States and Canada. Psoriasis has proven to be a difficult disease to treat and treatment failures, even with newer biologic therapies, are not uncommon. The vast majority of clinical data for these medications is derived from treatment of biologic-naive patients, or patients who have not responded to, or lost response to, or not tolerated systemic therapy for psoriasis. There is currently little data available on therapeutic response of a second biologic therapy after loss of response, or no response, to the first biologic therapy initiated. It has become common clinical practice to switch medications that are structurally distinct but therapeutically similar in order to achieve an improved clinical outcome. Therapeutic interchange now is being applied to the biologic agents used to treat psoriasis.

OBJECTIVES
Using a proof of concept study, describe the response of etanercept after adalimumab has failed to produce a satisfactory response in moderate to severe plaque psoriasis.

METHODS
A total of 10 biologically naive patients with moderate to severe psoriasis who were initiated on adalimumab for at least 12 weeks but had a Physician's Global Assessment (PGA) of mild or worse were transitioned to commercial etanercept 50 mg twice weekly (BIW) for 12 weeks followed by a dose reduction to 50 mg once weekly (OW) for an additional 12 weeks. Ethics approval was obtained and the study registered with ClinicalTrials.gov (NCT00833729). The primary outcome measured was the mean change in Physician?s Global Assessment (PGA) score (range 0-5) from baseline (when the first etanercept injection is given) to 12 weeks of etanercept therapy. The secondary outcomes measures included the mean change in Dermatology Quality of Life Index (DLQI), mean change in body surface area (BSA) covered in psoriasis, Subject's Global Assessment of disease (SGA), proportion of patients achieving an improvement in PGA score from baseline to 12 weeks and again at 24 weeks and safety.

RESULTS
Overall, there were significant favorable changes in all outcomes measured (PGA, SGA, BSA and DLQI) with respect to etanercept's efficacy after an inadequate response to at least 12 weeks of adalimumab therapy. There were no significant safety issues noted especially during the transition period from adalimumab to etanercept. ClinicalTrials.gov identifier: NCT00833729.


Miriam Louisa Rothschild was born at Ashton Wold, Northampton, on 5 August 1908 and died there on 20 January 2005, at the age of 96. She had no traditional education, but was tutored in natural history by her father and her uncle. Her first scientific studies were on parasites of marine snails and seabirds, but one of her principal achievements was the six–volume work cataloguing the Rothschild flea collection over a 30–year period. Her other main area of research was the chemical ecology of insects, particularly in mimicry, and the sequestering of toxic compounds from plants, in which she was a pioneer. She was still actively working in this area at the time of her death. Parts of her house and glasshouses were modified for research, but much of her chemical ecological work was performed in collaboration with some of the best natural–product chemists in the world. Nature conservation was dear to her heart and she developed the production of wildflower seeds on her farm and techniques for their establishment; she also lobbied energetically on behalf of nature reserves. She combined all this with the management of a large estate including a profitable farm, and was much loved by her tenants.


Abstract Fault reactivation, during coal mining subsidence, has been documented in the coalfields of Great Britain for at least the past 150 years. This often results in the generation of a scarp, fissure, graben or compression hump on the ground surface. These features subsequently may severely damage houses, other structures, transport networks, utilities and land. An aim of this paper is to demonstrate that mining-induced fault reactivation does not exist only in Britain but has also been observed or recorded in many other parts of the world as a result of the mining of coal, metalliferous ore-bodies and the abstraction of fluids. Examples are provided from Europe, USA, Australia, Canada, South America, Caribbean, Africa, Asia and Russia. Fault reactivation as a result of the mining of coal is the most commonly recorded and this probably reflects the long, complex mining history that has taken place in the more densely populated and urbanized parts of Europe, where there has been a greater potential for fault reactivation to cause damage to the built environment. Less reported are the examples of fault reactivation caused by the mining of metalliferous ore-bodies in more remote and sparsely populated parts of the world. Here, reactivated faults tend to be of little consequence to people and structures, therefore there has not been the need for reactivated faults to be investigated. Fault reactivation caused by groundwater, brine, oil and gas abstraction (in the USA) generates some of the largest scarps, which are recorded to be up to some 16 km long and 1 m high. Where these occur in seismically active tectonic zones it may be difficult to distinguish faults generated by fluid abstraction and those generated by earthquake activity. This paper also aims to provide some clarity to the understanding of fault reactivation, by drawing attention to and summarizing the principal effects of mining-induced fault reactivation.


Address space layout randomization (ASLR) is an important first line of defense against memory corruption attacks and a building block for many modern countermeasures. Existing attacks against ASLR rely on software vulnerabilities and/or on repeated (and detectable) memory probing. In this paper, we show that neither is a hard requirement and that ASLR is fundamentally insecure on modern cachebased architectures, making ASLR and caching conflicting requirements (ASLR⊕Cache, or simply AnC). To support this claim, we describe a new EVICT+TIME cache attack on the virtual address translation performed by the memory management unit (MMU) of modern processors. Our AnC attack relies on the property that the MMU's page-table walks result in caching page-table pages in the shared last-level cache (LLC). As a result, an attacker can derandomize virtual addresses of a victim's code and data by locating the cache lines that store the page-table entries used for address translation. Relying only on basic memory accesses allows AnC to be implemented in JavaScript without any specific instructions or software features. We show our JavaScript implementation can break code and heap ASLR in two major browsers running on the latest Linux operating system with 28 bits of entropy in 150 seconds. We further verify that the AnC attack is applicable to every modern architecture that we tried, including Intel, ARM and AMD. Mitigating this attack without naively disabling caches is hard, since it targets the low-level operations of the MMU. We conclude that ASLR is fundamentally flawed in sandboxed environments such as JavaScript and future defenses should not rely on randomized virtual addresses as a building block.


Alumina has been extensively used as a catalyst support material. It exists in several different phases namely y, r], 8,0 and a.

Phase transformations (eg y -» 8 0 —> a) can occur at well defined temperatures. If transformations occur during catalyst use, then the activity of the catalyst can be reduced significantly.

In this project, the effect of addition of metals to ti-A120 3 was investigated in an effort to stablise the high surface area phase at high temperatures. The following ions were added at 1 and 3wt% loadings' Ba2+, Ca2+, Ce3+, Cs+, La3+ and Zr4*.

In this investigation the order of the T|-A120 3 stablisation at 1270K was found to be as follows:

La3+ > Ce3+ = Cs+ > Zr4* « Ba2+ - Ca2+

Chemisorption measurements on Pt/n-Al20 3 catalysts, showed that the maximum dispersion of platinum (Pt) was obtained at a 3wt% loading. Catalyst samples containing this loading of Pt on tj-A120 3 were then prepared with the incorporation of either of the ions, La3+, Ce3+, Cs+ and Sn4+ The method of preparation of these samples was vaned by using either co-impregriation or step impregnation and the activity of the resulting catalysts was tested using the reaciton,

iso - C4 H10 + 0 2 ------> PRODUCTS

the most active catalyst sample was found to be lwt%Cs, 3wt%Pt/n-Al20 3, having a catalytic activity of up to 10 times greater than a 3wt% Pt/n-Al20 3.


Abstract The COI gene as the core of the DNA barcoding system for animals has received significant attention. The observed wide overlap between intra- and interspecific sequence variability has led researchers to envisage the primary COI-based method. The sequences of 16S rDNA, COI, and Cyt b genes of Nezara virudula (L.) (Hemiptera: Pentatomidae) from 13 countries and the same sequences of N. antennata Scott were chosen as molecular markers to analyze the intra- and interspecific relationships between the closely related species in this study. The results support that Cyt b gene may be a good candidate alongside COI, when the combined factors of geographic variation and closely related species are taken into account.


Despite its relatively low incidence, Listeria monocyto genes is an important food borne
pathogen due to the seriousness of symptoms in susceptible population groups. Listeria
spp. are ubiquitous and are difficult to eradicate from the smallgoods environment. The
pathogen is destroyed during heat treatment, however post-processing contamination can
occur. Because L. monocyto genes can grow at 4°C on vacuum- and/or modified
atmosphere packed (VP, MAP) smallgoods that typically have a shelf life of six to eight
weeks, dangerous growth of the organism can occur in the absence of control measures.
Several international listeriosis outbreaks involving smallgoods attest to this.
This thesis investigated the incidence of Listeria spp. in Australian smallgoods, and the
influence of interspecies bacterial competition on growth of L. monocytogenes.
The first part of this study comprised a survey of 100 smallgoods products to investigate
the incidence of L. monocyto genes in Australian processed meats. Although no
endogenous L. monocyto genes strains were isolated during this study, other Listeria spp.
were occasionally found. This encouraging finding suggests that the increasing
application of HACCP and GMP by Australian smallgoods producers has decreased the
incidence of L. monocyto genes in processed meats.
A substantial part of this thesis investigated the potential control of L. monocyto genes by
competition with endogenous lactic acid bacteria (LAB). The study included exploring
the basis of the "Jameson Effect", a phenomenon that occurs when bacteria are grown in
mixed cultures and inhibition of growth of all species is observed when one species
reaches stationary phase, (i.e. 'maximum population density', MPD, or 'maximum
carrying capacity', MCC of the environment). The "Jameson Effect" may be caused by a
number of factors including; for example, bacteriocins, organic acids and nutrient
depletion. This study explores the role of non-specific factors (i.e. pH and nutrient
depletion) in the "Jameson Effect" and, by inference, the importance of species- specific
interactions. Endogenous LAB for use in competition studies were isolated from commercial sliced
ham and identified. These strains, Lactobacillus sakei, Leuconostoc mesenteroides, and
Leuconostoc carnosum, are commonly found on VP/MAP processed meats.
Another substantial aspect of the thesis was to determine whether nutrient depletion, pH
or excreted soluble metabolites could explain the "Jameson Effect" for inhibition of
L. monocytogenes (Scott A). The results of the study suggests that competition among
bacteria for nutrients is a major factor leading to the "Jameson Effect" and that there is
little need to invoke production of species- specific inhibitors to explain the effect.
Initial experiments to investigate the nature of the "Jameson Effect" were conducted in
simple broth systems. These studies found that low pH and the presence of bacterial
metabolites in the broth medium did not reduce MPD in the presence of adequate
nutrients. This suggested that the "Jameson Effect" observed in broth systems could
simply be symptomatic of nutrient depletion.
In support of this conclusion, consistent results were obtained in MAP ham studies
undertaken to validate results of the broth studies under realistic commercial conditions.
Thus, it was concluded that the role of lactic acid bacteria (which dominate VP/MAP
processed meats) should not be underestimated when attempting to understand and
control the risk of L. monocyto genes in refrigerated, VP/MAP processed meats.


This overview of research on the relationship between behavior and culture is organized as follows. The first section relates how cross-cultural psychology, or cultural psychology, since it emerged in the mid 20th century has reflected a continuous tension between how and how much humans are the same psychologically and to what extent there is cultural specificity in psychological functioning. The second section on the charm of differences argues that research is often biased towards finding differences rather than cross-cultural invariance. The third section briefly outlines problems of cultural bias, or lack of equivalence, in assessment across cultural populations and its implications for interpretation of data. The fourth section makes explicit a theme that is embedded in other sections and reflected in the title, namely the psychological organization of cross-cultural differences. The section challenges the tendency to conceive of such differences as being organized in broad dimensions or psychological functions. This tendency to over-generalize is illustrated in the fifth section for various traditions of research, including the recent tradition of cultural neuroscience where the increasing contributions of Chinese researchers are particularly evident. An outlook and some conclusions are presented in the final section.


To determine whether acute caffeine ingestion improves high-intensity intermittent exercise performance, 17 college-level, competitive athletes (9 males, 8 females, mean age 22 years) performed caffeine and placebo trials in a double-blind randomized study. Caffeine and placebo (lactose) doses of 6 mg/kg body weight (rounded to nearest 1 00 mg) were given in 100 mg capsules; a dose consistently shown to produce urine caffeine levels below the maximum permitted by the International Olympic Committee. Habitual caffeine consumption, usual physical activity level, and food intake for 3 days prior to each trial were determined by questionnaire. At each trial, one week apart, subjects performed three 30 second sprints on a treadmill (7.5 mph, 20% incline) separated by 2 minutes of walking, followed by a final sprint to exhaustion. Time to exhaustion (TM-EXH) was recorded and ranged from 20-90 seconds. Subjects reported a rating of perceived exertion (RPE) at the end of each sprint. Fingertip blood lactate (LACT) was measured following the third 30 second sprint, final sprint, and after 5 minutes of recovery. Respiratory variables were measured throughout the trial and the respiratory exchange ratio (RER) was determined for each sprint and recovery period within each trial. Repeated measures ANOVA showed no significant differences between the caffeine and placebo trials for TM-EXH, RPE, LACT, or RER. However, although not significant, there was an average increase in TM-EXH during the caffeine trial by 2 seconds (4%); with 6 of9 males and 5 of8 females running longer during the caffeine trial. Habitual caffeine consumption did not appear to influence the results. In conclusion, the ingestion of caffeine prior to high intensity intermittent exercise seems to improve performance by a narrow and statistically non-significant margin.


States party to the 1949 Geneva Conventions and Additional Protocol I of 1977 have an obligation to take measures necessary to suppress all acts contrary to their provisions. Moreover, States must investigate war crimes allegedly committed by their nationals or on their territory, and other war crimes over which they have jurisdiction, such as on the basis of universal jurisdiction, and, if appropriate, prosecute the suspects. In accordance with these obligations and the limits they impose, States may adopt certain measures during and in the aftermath of armed conflicts to promote reconciliation and peace, one of which is amnesties. International humanitarian law (IHL) contains rules pertaining to the granting and scope of amnesties. Specifically, Article 6(5) of Protocol II additional to the Geneva Conventions relating to non-international armed conflicts (NIACs) provides that, at the end of hostilities, the authorities in power shall endeavour to grant the broadest possible amnesty to persons who have participated in the armed conflict, or those deprived of their liberty for reasons related to the armed conflict. Importantly, under customary IHL (as identified in Rule 159 of the ICRC customary IHL study), this excludes persons suspected of, accused of, or sentenced for war crimes in NIACs.


Dominick Browne, (1787 - 1860), became the first Lord Oranmore and Browne, the title Oranmore being taken in view of the family lands and property at Oranmore, Co. Galway. The Browne family were the largest landowners in Connaught at that time. The Brownes had 13 country houses throughout Connaught, including Ashford Castle at Cong. They owned 54,000 acres.He was made a Privy Councillor for Ireland in 1834 and became one of twenty eight elected representative Irish Peers. He spent vast sums of money on electioneering. It is said that on one election he spent #40,000, of which #600 was spent on lemons for punch. The Great Famine completed his ruin. With the exception of Castlemacgarrett, 2000 acres, he had to sell off all his other estates in the encumbered Estates Court. The whole of the Galway property, some of which had been in the family for 600 years, then passed from the Browne family. Dominick Browne descends from Mary Prendergast, who was a descendant of Maurice de Prendergast who's father Gerald came to Ireland with Strongbow during the Norman invasion in 1170. Castlemacgarrett Old, depicted in the background of this image, was once the ancestral home of the Prendergast Family, but a large part of the property of Castlemacgarrett had been in the possession of the Brownes for over 5 centuries before Geoffrey Browne married into the Prendergast family. The old house became unsafe, so Geoffrey and his wife Mary Prendergast built a new house in 1694. This new home lasted for several generations until it was destroyed by fire in 1811. After the fire of 1811, Dominick Browne,built the part of the present castle with its tower, on the right hand side of the main entrance. (www.ballindineschool.com/castlemacgarrett.html)
Barrett had painted another portrait of Dominick Browne which is thought to be from an earlier year; see image cgjc0943.


This thesis addresses the 'dilemma' between justice and finality when the validity
and effect of a judgment or an award of an international tribunal are challenged,
whether by means of appeal, annulment or revision. The tension between the two
principles has been misconstrued as a 'dilemma', whereas in reality they reflect a
dynamic relationship between intrinsic and extrinsic aspects of international dispute
settlement. Justice is the objective of international adjudication and arbitration,
encompassing legality, legitimacy and effectiveness. Finality is a principle invented
to support the attainment of justice, and to protect legal certainty against endless
challenges. Finality without justice undermines legitimacy of a dispute settlement
system.
The context for this analysis is recent and conflicting tendencies relating to ICSID
annulment proceedings in international investor-State arbitration. The annulment
decision in CMS v. Argentina triggered serious concerns on how 'errors' and
'lacunae' in international judgments are left untreated, at a time when the rule of law
has become a prime consideration in the international sphere too. The three
jurisdictions examined highlight different aspects of this issue. The ICJ is the
birthplace for revision of international judgments, and the principal judicial organ of
the international community. The WTO AB is the only appellate mechanism
functioning in State-State disputes in the international level. Finally, ICSID is the
most prolific institutional arbitration forum in public international law, and its
annulment procedure forms the terrain where the relationship between justice and
finality is discussed more often.
The thesis offers a revised theory of interpretation of the premises of legal recourse
against international judgments, in the absence of a 'World Appellate Court'. It
concludes that justice as 'rule of law' and as 'right process' calls for manifest errors
to be addressed by effective legal recourse. The principle of finality can only operate
in furtherance of justice, not against it.


New product development (NPD) can be described as both complex and multidisciplinary, and also as an activity that often requires significant amounts of design knowledge. Typically, there will be a large body of knowledge that designers can call upon, and use, during the design process from many areas including human factors, materials, business, manufacturing technologies and so on. The provision of this knowledge to designers during the design process is vital to the successful development of the product or system being designed, and to the future competitiveness of the company involved.

Given that even the most routine of design tasks is dependent upon vast amounts of expert knowledge and supporting information, there is an obvious need for some sort of support which will free designers from much of the drudgery involved in searching and locating appropriate knowledge.

This paper presents the findings from an initial review of designers knowledge needs in small-to-medium sized enterprises (SMEs) who are involved in new product design and development. This review forms part of a larger ongoing study which is concerned with the development of a support framework for representing and providing design knowledge.


The research on which this paper is based reveals the complex and differentiated outcomes of a statutory minimum wage. The primary objective of this research was to determine the extent to which the Sectoral Determination for Farm Workers is implemented on selected farms in the Eastern Cape. The experiences of farm workers are largely absent from existing studies of minimum employment conditions in the agricultural sector. Following a brief overview of the provisions in the sectoral determination, this article outlines some of the problems associated with the enforcement of statutory minimum wages, considers the impact of statutory minimum wages on remuneration and labour relations, and tracks changes in wage levels before and after the introduction of the sectoral determination. The most salient findings of the research include the following: First, farmers are complying with the provisions of the sectoral determination on a selective basis.
Second, although wages have increased, a significant portion of the workers interviewed still did not receive the minimum wage.
Third, the sectoral determination has not fundamentally altered the working, living and tenure conditions of farm workers. Finally, farmers seem able to absorb rising wage costs through selective compliance, work intensification, increased deductions and a strategic use of female and casual labour.


The Brisbane Ranges area, situated 80 km west of Melbourne and 30 km north-west of Geelong, is extraordinarily rich in diversity. With basalt grasslands, heathy woodland, alluvial soils, buckshot gravel and granite rocks, it boasts more than 430 species of native plants.

Wildflowers of the Brisbane Ranges contains magnificent photographs of more than 400 species, many of them orchids, including rare and vulnerable species such as the Naked Sun Orchid (Thelymitra circumsepta) and the Hyacinth Orchid (Dipodium pardalinum).

A list of references, colour guide, glossary, comprehensive index and a soil type map have been included, to assist the reader in locating and identifying the different species.

This full colour guide is the culmination of more than a decade of painstaking observation. It will help both the casual visitor and the keen naturalist to locate and identify an extensive range of wildflowers from this exceptional part of Victoria.


The cultural sector faces the conundrum of proving its value in a way that can be understood by decision-makers. As Smith (2010b) has noted, arts and cultural organisations face a 'cooler climate' than the one that prevailed during the early 2000s. As a result it will not be enough for arts and culture to resort to claiming to be a unique or special case compared with other government sectors (Matarasso 2009). Since the 1980s the value of the cultural sector has been demonstrated through the lens of 'impact', whether economic (e.g. Myerscough 1988) or social (e.g. Matarasso 1997). However in recent years there has been recognition, both within central government and in parts of the publically funded cultural sector, of the need to more clearly articulate the value of culture using methods which fit in with central government's decision-making. Thus the cultural sector will need to use the tools and concepts of economics to fully state their benefits in the prevailing language of policy appraisal and evaluation (Bakhshi, Freeman and Hitchen, 2009).


The deductions that may be drawn from the results of these experiments are as follows: That the normal vital resistance of rabbits to infection by streptococcus pyogenes (erysipelatos) is markedly diminished through the influence of alcohol when given daily to the stage of acute intoxication. That a similar, though by no means so conspicuous, diminution of resistance to infection and intoxication by the bacillus coli communis also occurs in rabbits subjected to the same influences. And that, while in alcoholized rabbits inoculated in various ways with staphylococcus pyogenes aureus, individual instances of lowered resistance are observed, still it is impossible to say from these experiments that in general a marked difference is noticed between alcoholized and non-alcoholized animals as regards infection by this particular organism. It is interesting to note that the results of inoculation of alcoholized rabbits with the erysipelas coccus correspond in a way with clinical observations on human beings addicted to the excessive use of alcohol when infected by this organism. In the course of the work an effort was made to determine if, through the oxidation of alcohol in the tissues to acids of the corresponding chemical group, the increase of susceptibility could be referred to a diminution in the alkalinity of the blood as a result of the presence of such acids. The number of experiments thus far made on this point is too small to justify dogmatic statements, but from what we have gathered there is but little evidence in support of this view. Throughout these experiments, with few exceptions, it will be seen that the alcoholized animals not only showed the effects of the inoculations earlier than did the non-alcoholized rabbits, but in the case of the streptococcus inoculations the lesions produced (formation of miliary abscesses) were much more pronounced than are those that usually follow inoculation with this organism. With regard to the predisposing influence of the alcohol, one is constrained to believe that it is in most cases the result of structural alterations consequent upon its direct action on the tissues, though in a number of the animals no such alteration could be made out by macroscopic examination. I am inclined, however, to the belief, in the light of the work of Berkley and of Friedenwald, done under the direction of Prof. Welch, in the Pathological Laboratory of the Johns Hopkina University, that a closer study of the tissues of these animals would have revealed in all of them structural changes of such a nature as to indicate disturbances of important vital functions of sufficient gravity to fully account for the loss of normal resistance. The conspicuous influence of the alcohol on the gastric mucous membrane in many of these animals, with the consequent disturbance of nutrition, is undoubtedly the explanation of the marked loss in body weight that was observed in many of the animals employed in these experiments. In this light the susceptibility induced by alcohol to excess is somewhat analogous to that induced by starvation, where we see the resistance of animals to particular forms of infection very markedly diminished.


In this thesis, I investigated the ties between museums and communities. In my research, I moved beyond old museum methods of exclusivity instead exploring new directions for inclusive museum practice, specifically in the area of exhibition design processes. The design study I undertook in this thesis borrows on several early efforts of community-based exhibit making, but moves beyond them in one significant way: an integrated design process that includes community WITHIN the design. While community organizations and citizens have been involved in conceptualizing exhibits and discussions about content, my interest lies in how communities emerge through linking existing organizations, groups, and others interested in conversations about design and space. And while cycling represents the specific subject matter of the exhibition herein, I assert that the participatory process applies to any community-based project in a museum setting. Significantly, I learned that communities exist outside the physical realm and that individuals come together in unanticipated ways around any exhibit subject. This, perhaps, represents the single greatest finding of my work, all of which began with an idea about my interest to challenge what museums do and who they represent.


Ductal carcinoma in situ (DCIS) of the breast is a noninvasive form of breast cancer that has increased in incidence over the past several decades secondary to screening mammography. DCIS now represents 20–30% of all newly diagnosed cases of breast cancer. Patients with DCIS typically present with an abnormal mammogram, and diagnosis is most commonly obtained with an image-guided biopsy. Historically, mastectomy was considered the primary curative option for patients with DCIS. However, treatment of DCIS continues to evolve, and now treatment strategies also include breast-conserving therapy, which consists of local excision followed by radiation therapy or local excision alone. Multiple randomized trials have confirmed a decrease in ipsilateral breast tumor recurrence in patients treated with local excision followed by radiation therapy compared with local excision alone. Ongoing clinical trials attempt to identify a subgroup of DCIS patients at low risk for recurrence who may not benefit from radiation therapy. In addition, because the majority of ipsilateral breast tumor recurrences occur near the original primary tumor site, partial breast irradiation is currently under investigation as a treatment option for DCIS patients. Randomized trials have shown tamoxifen can reduce the risk of ipsilateral and contralateral breast tumor recurrences while the role of aromatase inhibitors is the subject of current clinical trials. DCIS represents a complex pathologic entity, and treatment optimization requires a multidisciplinary approach.


The analysis of imaging data derived from micro-Fourier transform infrared (mFTIR) microscopy is a powerful tool allowing the analysis of microplastics enriched on membrane filters. In this study we present an automated approach to reduce the time demand currently needed for data analyses. We developed a novel analysis pipeline, based on the OPUS© Software by Bruker, followed by image analysis with Python and Simple ITK image processing modules. By using this newly developed pipeline it was possible to analyse datasets from focal plane array (FPA) mFTIR mapping of samples containing up to 1.8 million single spectra. All spectra were compared against a database of different synthetic and natural polymers by various routines followed by benchmark tests with focus on accuracy and quality. The spectral correlation was optimized for high quality data generation, which allowed image analysis. Based on these results an image analysis approach was developed, providing information on particle numbers and sizes for each polymer detected. It was possible to collect all data with relative ease even for complex sample matrices. This approach significantly decreases the time demand for the interpretation of complex FTIR-imaging data and significantly increases the data quality.


As a consequence of global changes to trade policy, there are likely to be significant impacts on international agricultural trade. Clearly producers in the European Union (EU) will experience considerable changes to the structure of their industry, and for a country such as New Zealand, heavily dependent on agricultural exports, changes to policy and markets have the potential to significantly affect the economy. The potential competition from China in terms of agricultural commodities as well as its potential as an export destination for NZ are also important considerations. This paper presents an analysis of the impact of both World Trade Organisation (WTO) and Common Agricultural Policy (CAP) reform in the agricultural sectors of the EU, New Zealand, and China. The analysis covers the livestock sectors of these countries. The model used for this analysis is the LTEM (Lincoln Trade and Environment Model).


With the growing importance of miniaturized energy applications and the development of micro Total Analysis Systems (μTAS), we have realized microfluidic devices, namely, magnetic micropumps, microfluidic fuel cells and membrane-based protein preconcentrators, all having high application potential in future. The choice of rapid prototyping microfabrication technologies and the selection of affordable materials are important aspects, when thinking of commercialization. Thus, we have employed powder blasting, polymer molding and assembly technologies during devices fabrication throughout the thesis. The first type of microfluidic device that we present is a poly(methyl methacrylate) (PMMA) ball-valve micropump with two different designs of the electromagnetic actuator, as optimized by the finite element method. The integration of a permanent magnet in a flexible polydimethylsiloxane (PDMS) membrane, which is clamped into PMMA structure, is proposed for providing a large stroke of the pumping membrane, making the micropump bubble-tolerant and self-priming Focusing on low power consumption for μTAS integration, another type of magnetic micropump with active valves is realized. It consists of a microfluidic chamber structure in glass that is assembled with a PDMS sheet, which comprises two valving membranes and a central actuation membrane, having each an integrated permanent magnet that is peristaltically actuated by a rotating arc-shaped permanent magnets assembly. A lumped circuit model is developed to predict and describe the frequency-dependent flow rate behavior for this type of pump. Powder blasting and PDMS molding rapid prototyping technologies are employed for realization of these two types of micropumps. Fuel cells with fluid delivery and removal options, having chemical reaction sites and electrode structures that can be realized in a microfluidic format, have high potential for applications. Therefore, microfluidic direct methanol fuel cells with embedded ion- permselective medium are studied and such type of fuel cell is realized by integrating a narrow Nafion strip in a molded elastomeric structure. A mechanical clamping assembly technology enables leakage-free operation and stable performance. The characterization reveals its output power density, using H2O2-based oxidant, is among the high-performance direct methanol fuel cells in microscale. Re-using the technology of the fuel cell chip, with its particular ion-permselective Nafion membrane and assembly method, we also have developed a protein preconcentrator with high purification performance. Our device can preconcentrate negatively charged biomolecules located at the anodic compartment side of the Nafion strip within only a few minutes with a high preconcentration factor. Moreover, a complex microfluidic finite element model is proposed to study and understand the physics of the preconcentration effect. Finally, we conclude the thesis with an outlook on future developments based on our work of the project and on the assembly technologies for microfluidic device integration.


Several recent studies from both Greenland and Antarctica have reported significant changes in the water isotopic composition of near‐surface snow between precipitation events. These changes have been linked to isotopic exchange with atmospheric water vapor and sublimation‐induced fractionation, but the processes are poorly constrained by observations. Understanding and quantifying these processes are crucial to both the interpretation of ice core climate proxies and the formulation of isotope‐enabled general circulation models. Here, we present continuous measurements of the water isotopic composition in surface snow and atmospheric vapor together with near‐surface atmospheric turbulence and snow‐air latent and sensible heat fluxes, obtained at the East Greenland Ice‐Core Project drilling site in summer 2016. For two 4‐day‐long time periods, significant diurnal variations in atmospheric water isotopologues are observed. A model is developed to explore the impact of this variability on the surface snow isotopic composition. Our model suggests that the snow isotopic composition in the upper subcentimeter of the snow exhibits a diurnal variation with amplitudes in δ18O and δD of ~2.5‰ and ~13‰, respectively. As comparison, such changes correspond to 10–20% of the magnitude of seasonal changes in interior Greenland snow pack isotopes and of the change across a glacial‐interglacial transition. Importantly, our observation and model results suggest, that sublimation‐induced fractionation needs to be included in simulations of exchanges between the vapor and the snow surface on diurnal timescales during summer cloud‐free conditions in northeast Greenland.


Abstract: This study investigated a natural acid-base indicator which is extracted from plants in Kupang city. There are 14 plants that potential as a source of natural indicator for acid base titration, i.e, Kol Ungu (Brassica oleracea Capitata Group), Turi Merah flower (Sesbania grandiflora L. Pers), Belimbing Wuluh flower (Averhoa bilimbi L), Kaktus Merah fruit (Opuntia vulgaris Mill), Ruelia flower (Ruellia simplex), Flamboyan flower (Delonix regia), bugenvil flower (Bougainvillea spectabilis Willd.), Bayam Merah leaves (Amaranthus tricolor L.) Jamblang fruit (Syzygium cumini L.), Murbey fruit (Morus alba L.), Pinang fruit (Areca catechu L.), Sirih fruit (Piper betle L.), Kunyit (Curcuma longa Linn), and Nanas Kerang leaves (Rhoeo discolor). Plants extract shows a sharp color change in acid and base solution. Promising results as a natural indicator also shown in acid base titration which is have similar equivalent point to synthetic indicator. We can use these natural indicators as an alternative to synthetic indicator because they are found to be simple, very useful, cheap, easy to extract, accurate, and eco-friendly.  Keywords: plant, natural indicator, acid-base


Archaeomagnetic studies have been made of prehistoric aboriginal fireplaces occurring along the ancient shore of Lake Mungo, a dried out lake in southeastern Australia. Directions of magnetization preserved in ovenstones and baked hearths show that wide departures of up to 120° from the axial dipole field direction occurred about 30000 years ago. The determination of the variation in geomagnetic field strength from the baked material is complicated by non-ideal behaviour during Thellier's double heating method. The problem appears to arise from the subsequent (postfiring) formation of iron oxyhydroxides during a period in which the water level in the lake rose. During laboratory heatings these oxyhydroxides dehydrate causing the non-ideal behaviour observed. The ancient field strengths deduced are therefore probably minimum values. The geomagnetic excursion recorded between at least 30780 ±520 and 28140 ±370 years b.p. on the conventional radiocarbon time scale is associated with very high field strengths between 1 and 2 Oe (1 Oe » 79.6 A m_1). The field strength subsequently decreased to between 0.2 and 0.3 Oe after the excursion. This main excursion is referred to as the Lake Mungo geomagnetic excursion. There is evidence that a second excursion associated with low field strengths of 0.1-0.2 Oe occurred around 26000 years b.p. A review of geomagnetic excursions less than 40 000 years in age shows that it may be premature to assume that these are world-wide synchronous features. The range of ages and their groupings in different parts of the world may indicate they are temporary non-dipole features of continental extent. However, the duration of most excursions (order of 103 years) is very similar to that of polarity transitions and this could indicate they are aborted reversals.


Using a data set integrating information about researchers' funding and publications in Quebec (Canada), this paper identifies the main determinants of citation counts as one measure of research impact. Using two-stage least square regressions to control for endogeneity, the results confirm the significant and positive relationship between the number of articles and citation counts. Our results also show that scientists with more articles in higher impact factor journals generally receive more citations and so do scientists who publish with a larger team of authors. Hence the greater visibility provided by a more prolific scientific production, better journals, and more co-authors, all contribute to increasing the perceived impact of articles. All else being equal, male and female receive the same number of citations. These results suggest that the most important determinants of researchers' citations are the journals in which they publish, as well the collaborative nature of their research.


Look and learn to recall a wealth of everyday vocabulary in Hindi with this intuitive easy-to-use visual language dictionary. Whether it's for business or pleasure, pick up 6,000 key Hindi words and phrases on a range of subjects: from shopping and eating out, to sport and beyond quickly and easily. You can find every word you need to know fast using the clearly labelled colour illustrated scenes from everyday life. Plus, find helpful features on key Hindi nouns, verbs and phrases to improve your understanding. It is pocket-sized so you can take it wherever your travels take you.


The major focus of the present study is to assess the productivity gap and production shortfalls, to suggest
the location specific varieties, technologies, input and resource management to bring down the yield gap.
The results indicated that the annual growth rates were negative for cotton (-13.24 per cent), sunflower (-
6.12 per cent) paddy (-1.8 per cent), cumbu(-3.8 per cent), cholam (-1.17 per cent) and gingelly (-3.14
per cent) and it was positive in case of maize (24.81 per cent), greengram (10.73 per cent), coconut (4.10
per cent), chillies (2.99 per cent), blackgram (2.45 per cent) and banana (1.78 per cent). The yield gap
for paddy varies from 14 per cent to 36 per cent, pulse crop with 56 per cent to 67 per cent, oil seed crops
with 32.46 per cent to 72.15 per cent and cotton crop with 66.33 to 80.95 per cent. The suggested
potential varieties of paddy to reduce the yield gap are ADT 36, ASD 16, ADT 39, ASD 18 and MDU 5
and for blackgram Vamban 4 and Vamban 5.


[1] The Chukchi Sea (CS) circulation reconstructed for September 1990 to October 1991 from sea ice and ocean data is presented and analyzed. The core of the observational data used in this study comprises the records from 12 moorings deployed in 1990 and 1991 in U.S. and Russian waters and two hydrographic surveys conducted in the region in the fall of 1990 and 1991. The observations are processed by a two-step data assimilation procedure involving the Pan-Arctic Ice-Ocean Modeling and Assimilation System (employing a nudging algorithm for sea ice data assimilation) and the Semi-implicit Ocean Model [utilizing a conventional four-dimensional variational (4D-var) assimilation technique]. The reconstructed CS circulation is studied to identify pathways and assess residence times of Pacific water in the region; quantify the balances of volume, freshwater, and heat content; and determine the leading dynamical factors configuring the CS circulation. It is found that in 1990–1991 (high AO index and a cyclonic circulation regime) Pacific water transiting the CS toward the Canada basin followed two major pathways, namely via Herald Canyon (Herald branch of circulation, 0.23 Sv) and between Herald Shoal and Cape Lisburne (central branch of circulation and Alaskan Coastal Current, 0.32 Sv). The annual mean flow through Long Strait was negligible (0.01 Sv). Typical residence time of Pacific water in the region varied between 150 days for waters entering the CS in September and 270 days for waters entering in February/March. Momentum balance analysis reveals that geostrophic balance between barotropic pressure gradient and Coriolis force dominated for most of the year. Baroclinic effects were important for circulation only in the regions with large horizontal salinity gradients associated with the fresh Alaskan and Siberian coastal currents and the Cape Lisburne and Great Siberian polynyas. In the polynyas, the baroclinic effects were due to strong salinification and convection processes associated with sea ice formation.


Neural sequence-to-sequence models have been successfully applied to text compression. However, these models were trained on huge automatically induced parallel corpora, which are only available for a few domains and tasks. In this paper, we propose a novel interactive setup to neural text compression that enables transferring a model to new domains and compression tasks with minimal human supervision. This is achieved by employing active learning, which intelligently samples from a large pool of unlabeled data. Using this setup, we can successfully adapt a model trained on small data of 40k samples for a headline generation task to a general text compression dataset at an acceptable compression quality with just 500 sampled instances annotated by a human.


The present work reports the outcome of the GIMEMA CML WP study CML0811, an independent trial investigating nilotinib as front-line treatment in chronic phase chronic myeloid leukemia (CML). Moreover, the results of the proteomic analysis of the CD34+ cells collected at CML diagnosis, compared to the counterpart from healthy donors, are reported.
Our study confirmed that nilotinib is highly effective in the prevention of the progression to accelerated/blast phase, a condition that today is still associated with high mortality rates. Despite the relatively short follow-up, cardiovascular issues, particularly atherosclerotic adverse events (AE), have emerged, and the frequency of these AEs may counterbalance the anti-leukemic efficacy. The deep molecular response rates in our study compare favorably to those obtained with imatinib, in historic cohorts, and confirm the findings of the Company-sponsored ENESTnd study. Considering the increasing rates of deep MR over time we observed, a significant proportion of patients will be candidate to treatment discontinuation in the next years, with higher probability of remaining disease-free in the long term. The presence of the additional and complex changes we found at the proteomic level in CML CD34+ cells should be taken into account for the investigation on novel targeted therapies, aimed at the eradication of
the disease.


An efficient and accurate hybrid model of the Monte Carlo technique and the diffusion theory was developed to simulate the diffuse reflectance of light in a turbid slab due to an infinitely narrow light beam. The narrow beam was normally incident on the top surface of the slab. The hybrid model was accurate in modeling the diffuse reflectance near the light source, where the diffusion theory was most inaccurate. The hybrid model was much faster than a pure Monte Carlo method by a factor as great as several hundred, depending on the optical properties, the thickness of the slab, and the settings of the hybrid and the Monte Carlo computations. The computation speed of the hybrid model was insensitive to the optical properties of the medium, in contrast to the pure Monte Carlo technique. The diffusion theory was accurate in modeling both the diffuse reflectance far from the source and the diffuse transmittance. The hybrid model and the diffusion theory should be used in conjunction for efficient and accurate computation of diffuse reflectance and diffuse transmittance.