Insurmountable Hurdles Research Articles

Emergence of an Aware and Assertive Woman: A Study of Marital Relationship in the Novels of Anita Desai

Abstract: This paper deals with the study of marital relationship, one of the most complex, subtle and chameleonic human relationship, in the lives of the protagonists in the novels of Anita Desai. Through the depiction of this relationship, the novelist tries to foray into the deep recesses of her protagonists’ psyche and reveals their strivings to attain a meaningful pattern of life. Through the depiction of varied kind of protagonists, the novelist tries to show that some of her initial protagonists are quite immature, having myopic vision of life, who reflect rigidity in their personality. This extreme rigidity and egoism creates insurmountable hurdles for them in their inter -personal relations as well as adjustment with the flux of life. Various social customs and traditions which demand sacrifice and adjustment for their part are beyond their comprehension at all. The harrowing despair in their marital relations and lack of recognition in the family and society cumulatively thrusts them into circumscribed zones of isolation. On the other hand, some of her characters are made of strong stuff. They are quite mature and tend to face various vicissitudes of life with a mature, flexible and compromising attitude. Since they have a strong desire to achieve an authentic kind of existence and this zeal makes them flexible to evaluate the pattern of life in totality and eventually, they succeed in evolving a new harmonious pattern life at a higher level of maturity and wisdom.

Construction and Functionalization of Highly Strained N -Doped Zigzag Hydrocarbon Belts

Construction and Functionalization of Highly Strained <i>N</i> -Doped Zigzag Hydrocarbon Belts

Microbial | electrochemical CO2 reduction: To integrate or not to integrate?

Microbial | electrochemical CO2 reduction: To integrate or not to integrate?

Chebyshev expansion of spectral functions using restricted Boltzmann machines

Calculating the spectral function of two dimensional systems is arguably one of the most pressing challenges in modern computational condensed matter physics. While efficient techniques are available in lower dimensions, two dimensional systems present insurmountable hurdles, ranging from the sign problem in quantum Monte Carlo (MC), to the entanglement area law in tensor network based methods. We hereby present a variational approach based on a Chebyshev expansion of the spectral function and a neural network representation for the wave functions. The Chebyshev moments are obtained by recursively applying the Hamiltonian and projecting on the space of variational states using a modified natural gradient descent method. We compare this approach with a modified approximation of the spectral function which uses a Krylov subspace constructed from the "Chebyshev wave-functions". We present results for the one-dimensional and two-dimensional Heisenberg model on the square lattice, and compare to those obtained by other methods in the literature.

Exploring Three Core Psychological Elements When Treating Adolescents on the Autism Spectrum: Self-Awareness, Gender Identity, and Sexuality.

For those growing up on the autism spectrum, adolescence is associated with unique challenges. This narrative review explores three core psychological elements for clinicians to consider when treating adolescents on the autism spectrum: self-awareness, gender identity, and sexuality. Developmental tasks of adolescence include adaptation to a maturing mind and body, increased expectations for independence, and the ability to establish satisfying interpersonal relationships. What are welcome opportunities for non-autistic peers can become nearly insurmountable hurdles for autistic teens, which, in turn, could lead to crisis, particularly if skills needed for success in managing these tasks have not yet been acquired.

Deprivation or Circumvention of the UN’s Immunity

Abstract The immune system is supposed to protect one’s body from harmful germs, but sometimes it may attack a healthy part of the body itself—this is called an ‘autoimmune disease’. Although the founders of the United Nations (UN) equipped it with such immunities as are necessary for the fulfilment of its purposes, it seems that its jurisdictional immunity is sometimes more detrimental to its proper functioning than protective of it, especially in the context of peacekeeping. The present study aims to discover a cure for this autoimmune disease. Immunities are, in general, under attack because they serve as insurmountable hurdles to holding those who exercise public authority accountable before domestic courts. Peacekeepers may harm the local population, but the UN’s immunity leads to the denial of justice in cases of third-party claims, which put pressure on the UN. However, neither deprivation nor circumvention of the UN’s jurisdictional immunity is a safe and holistic cure for this autoimmune disease. What we need to ensure is that the immune system functions as designed.

Simple-Structured Micromotors Based on Inherent Asymmetry in Crystalline Phases: Design, Large-Scale Preparation, and Environmental Application.

The key principle of designing a micro/nanomotor is to introduce asymmetry to a micro/nanoparticle. However, micro/nanomotors designed based on external asymmetry and inherent chemical and geometrical asymmetry usually suffer from tedious small-scale preparation, high cost, and/or complexity of external power and control devices, making them face insurmountable hurdles in practical applications. Herein, considering the possible distinct properties of different polymorphs, we propose a novel design strategy of simple-structured micromotors by introducing inherent asymmetry in crystalline phases. The inherent phase asymmetry can be easily introduced in spherical TiO2 particles by adjusting the calcination temperature to control the phase transition and growth of primary grains. The as-designed anatase/rutile TiO2 micromotors not only show efficient autonomous motions controlled by light in liquid media stemming from the asymmetric surface photocatalytic redox reactions but also have a promising application in environmental remediation due to their high photocatalytic activity in "on-the-fly" degradation of organic pollutants, facile large-scale fabrication, and low cost. The proposed design strategy may pave the way for the large-scale productions and applications of micro/nanomotors.

I.T. Roadmap for Enterprise Cloud Strategy

Any company needs to improve IT agility and efficiency to help drive aggressive business growth and reduce costs. Insurmountable hurdles are as follow: An inefficient and aging IT infrastructure and a subsequent spiralling spend in data centre operations. Infrastructure model is based on a technology-oriented approach, as opposed to a more agile and scalable service-oriented model. Enterprise wide Cloud Adoption is a strategic decision rather than a tactical or an operational decision. This paper proposes Roadmap for Enterprise Cloud Strategy.

Los Angeles v. Mendez: Proximate Cause Promise for Police Shooting Victims

Los Angeles County v. Mendez, the Supreme Court’s recent decision rejecting shooting victims’ excessive force claims, has been written off as yet another case in which police violence has no civil rights consequences. The Court found that the deputies who shot Jennifer Garcia and Angel Mendez fifteen times used reasonable force because Mendez was holding a BB gun. But the deputies barged in on Garcia and Mendez while they were napping on a futon in their home, and Mendez grabbed his BB gun to stand up and steady himself. The Court remanded the case with instructions to consider whether the defendants’ warrantless entry into the plaintiffs’ home, a constitutional violation not entitled to qualified immunity, was the proximate cause of the deputies’ deadly force. Justice Alito, writing for the Court, advised plaintiffs that “there is no need to dress up every Fourth Amendment claim as an excessive force claim.” The invitation to attempt recovery through an alternative legal theory could prove revolutionary for victims of police-involved shootings. So long as they can rely on common law tort principles to show that their injuries were proximately caused by an earlier constitutional violation, they might avoid excessive force precedent’s insurmountable hurdles, which, in recent cases like Plumhoff v. Rickard and Brosseau v. Haugen, has sanctioned nearly all forms of law enforcement deadly force. If plaintiffs can recover damages for shootings, then 42 U.S.C. § 1983 might once again serve some real deterrent purpose, forcing police officers to think before they shoot.

Obstacles in Secondary Analysis of Routine Data From Primary Care

Routinely recorded data from everyday ambulatory medical care are urgently needed for health services and systems research, but this faces major limitations in Germany. In 2018, European General Data Protection Regulation (GDPR) and new German Federal Data Protection Act (FDPA) become effective. Via simulated real-life scenarios it may be possible to find out if access to and utilization of routine data for research becomes easier or faces additional obstacles. General practitioners, information scientists, data trustees and privacy protection experts create concepts, processes and standards for lawful handling of routinely recorded data for secondary research and study their feasibility in 2 scenarios (anonymous and pseudonymous data utilization). From the point of view of technical assessment and privacy protection, technical and organizational obstacles are presented as well as the legal framework. Outdated software interface, insufficient maintenance by software vendors, burdens associated with organization and cost as well as poor IT standards place obstacles to systematic and longitudinal use of healthcare routine data. Future pan-European law for privacy protection will allow research utilization of ambulatory data in principle. However, there are persisting conflicts between individual (fundamental right of privacy protection) and public interests (research for quality and efficiency of public spending; European market's free exchange of goods and services). This becomes evident especially when using routine data via pseudonymization. Neither insurmountable hurdles by privacy protecting law nor a threat from Big Data are currently the major obstacles to secondary utilization of routine data but real-life problems at the technology and operational level. GDPR and FDPA that have become into effect in May 2018 have improved European legal unity and transparency of patients' interests. Tension between privacy protection of data on an identified or identifiable person and scientific utilization and exchange of such data in public interest necessitates additional legal clarification. One possible solution, an advanced and ready-to-use software interface, awaits implementation.

Reparations and the Colonial Dilemma: The Insurmountable Hurdles and Yet Transformative Benefits

The Seventh Annual Latina and Latino Critical Race Theory (LatCrit) Conference held in May 2002 at the University of Oregon, not unlike other efforts in the movement, addressed a panoply of challenging, provocative, and controversial issues. Perhaps one the most intellectually interesting and yet troubling panels addressed reparations for the inhabitants of United States' colonial territories. Specifically, the panel was titled Reparations, Redress, and Remedies: Undoing the Legacy of Colonialism and Imperialism. Members of the academy as well as a representative of Puerto Rico's Independence Party participated in a lively discussion and debate. Although the articles resulting from this panel touch upon Puerto Rico's colonial dilemma, not all addressed the issue of It is the topic of reparations that is the focus of this cluster introduction. The topic of reparations provokes strong feelings because, among other reasons, it is a request of the dominant culture to atone for past wrongs, primarily through monetary relief. For many, the response to any request for reparations, but particularly for a request from the inhabitants of Puerto Rico, would be: Why reparations? Not unlike reparations claims for Native Hawaiians, opponents to a Puerto Rican reparations effort would probably deem the reparations claims unavailing because the opponents simply would fail to perceive that any legal wrong has occurred. This cluster introduction will address this question of why reparations. Before addressing the nascent Puerto Rican reparations debate, a brief description of LatCrit theory is in order.

Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease.

Alzheimer’s disease (AD) is an incurable and debilitating chronic progressive neurodegenerative disorder which is the leading cause of dementia worldwide. AD is a heterogeneous and multifactorial disorder, histopathologically characterized by the presence of amyloid β (Aβ) plaques and neurofibrillary tangles composed of Aβ peptides and abnormally hyperphosphorylated tau protein, respectively. Independent of the various etiopathogenic mechanisms, neurodegeneration is a final common outcome of AD neuropathology. Synaptic loss is a better correlate of cognitive impairment in AD than Aβ or tau pathologies. Thus a highly promising therapeutic strategy for AD is to shift the balance from neurodegeneration to neuroregeneration and synaptic repair. Neurotrophic factors, by virtue of their neurogenic and neurotrophic activities, have potential for the treatment of AD. However, the clinical therapeutic usage of recombinant neurotrophic factors is limited because of the insurmountable hurdles of unfavorable pharmacokinetic properties, poor blood–brain barrier (BBB) permeability, and severe adverse effects. Neurotrophic factor small-molecule mimetics, in this context, represent a potential strategy to overcome these short comings, and have shown promise in preclinical studies. Neurotrophic factor small-molecule mimetics have been the focus of intense research in recent years for AD drug development. Here, we review the relevant literature regarding the therapeutic beneficial effect of neurotrophic factors in AD, and then discuss the recent status of research regarding the neurotrophic factor small-molecule mimetics as therapeutic candidates for AD. Lastly, we summarize the preclinical studies with a ciliary neurotrophic factor (CNTF) small-molecule peptide mimetic, Peptide 021 (P021). P021 is a neurogenic and neurotrophic compound which enhances dentate gyrus neurogenesis and memory processes via inhibiting leukemia inhibitory factor (LIF) signaling pathway and increasing brain-derived neurotrophic factor (BDNF) expression. It robustly inhibits tau abnormal hyperphosphorylation via increased BDNF mediated decrease in glycogen synthase kinase-3β (GSK-3β, major tau kinase) activity. P021 is a small molecular weight, BBB permeable compound with suitable pharmacokinetics for oral administration, and without adverse effects associated with native CNTF or BDNF molecule. P021 has shown beneficial therapeutic effect in several preclinical studies and has emerged as a highly promising compound for AD drug development.

The Inefficient Efficiency Defense: St. Luke's and the Efficiency Analysis

Today, efficiencies are considered to play a critical role during the Clayton Act Section 7 analysis. However, despite the 1997 revision of the Merger Guidelines, no prima facie case has yet been rebutted with an efficiency claim. This paper looks at the importance of an efficiency story, specifically in the healthcare industry, through the lens of the recent St. Luke’s case. In St. Luke’s, the Court found that absent a decrease in price efficiencies, quality efficiencies would not offset any anticompetitiveness of the transaction. This paper examines the importance of quality efficiencies in the healthcare industry and how these efficiencies could potentially benefit consumers even more than price decreases. Additionally, this paper looks at the importance of having a sound burden-shifting framework for a Section 7 analysis. Specifically, I argue that in St. Luke’s the district court seemed to treat market shares as more than just a “convenient starting point,” ultimately causing insurmountable hurdles in presenting an efficiency defense during litigation. Finally, this paper discusses why an efficiency defense should not involve having to disprove all the potential negatives on competition.

Success is not final and failure is not fatal.

DOI: 10.1200/JCO.2014.55.2828 We cannot always anticipate how patients will respond to information we present them—even startlingly good news. Clinical oncology by its very nature is fraught with emotion and is full of uncertainty and ambiguity. Conveying uncertainty remains a major component of an oncologist’s clinical work. The fear, angst, and sometimes anger encountered with the development or progression of metastatic disease are common emotions in clinic. We are less familiar with the uncertainty and accompanying dilemmas presented by successful therapy in the metastatic setting. For the last 3 years, I have been treating Mrs P, a woman with multifocal metastatic disease. I have always been direct with her regarding the situation and have talked frankly about the fact that her sarcoma is not curable and treatment options limited. I am quite sure that she has no doubts about the palliative aims of treatment. On this particular day, she was due to see the nurse practitioner, so when I walked into the room, she sensed that it was because I had bad news. She is intelligent, sophisticated, and forthright and does not hesitate to articulate her opinions. On this busy clinic day, it was an all too familiar conversation regarding the development of recurrent disease, the uncertainties of trial participation, and the time commitment involved. For me, this was a wellrehearsed and easily delivered dialogue. Mrs P, who was also a master of communication skills, detected uncertainty in the nurse practitioner’s approach and recognized that my unexpected appearance signaled trouble. She treated the medical system with suspicion and at times with disdain. She expressed her thoughts about my treatment recommendation and the proposed clinical trial with candor and directness. In the end, she opted for the trial, despite the required effort and commitment. She did well. Months went by and restaging scans showed continued improvement. She tolerated the intravenous drug well. She and her husband were delighted. Her visits became routine and straightforward, the results consistently good. I would often quote my surgical colleague’s adage to her: “A quick visit is always a good visit.” On several occasions, she mentioned that she did “not want to be on this treatment forever.” I stuck to my narrative that, in this case, prolonged chronic therapy would be the best-case option for someone with her advanced stage of disease. After 1.5 years on therapy, restaging scans demonstrated a radiologic complete response. She tolerated the drug extremely well. So at this point, we began to discuss again the distance she had to travel to receive treatment and how long she ought to continue on the drug. Both the patient and her husband were getting tired of the journey and the uncertainty regarding the length of therapy. It was clear to all of us that she could not receive the investigational agent off trial. We had looked into that option with her, but there were almost insurmountable hurdles in getting this trial open (for a rare disease) at her local hospital. So Mrs P’s basic choice was to continue to travel to receive her maintenance therapy or stop. Her question remained: “How long must I continue?” Mrs P and her husband knew that stopping treatment would likely mean return of cancer. Although it was successful, we harbored no fantasy that therapy was curative, and it was this critical fact that she found unbearable. Her questions exposed other concerns, both financial and personal. From that point on, clinic visits became increasingly more challenging and testy. We would discuss the excellent scan results, continuing treatment or stopping, and then end the conversation by acknowledging the lack of data regarding outcome. We spoke of other patients who had continued on chronic therapy for metastatic disease with all the associated physical and emotional challenges of such protracted treatment. She appreciated the benefit she had obtained, and I would remind her that tragically other patients were not as fortunate. I could appreciate her concerns, the disease was uncurable, and she was essentially in limbo. Yes, the trial medication was good and she had derived clear benefit, but the choice was to continue with therapy indefinitely or stop. She was frustrated and derived no comfort from hearing other patients’ stories or any anecdotal evidence I could provide. More than 2 years after starting therapy, she returned with her husband for another routine scan. And once again, the scan showed a maintained radiologic complete response. I thought JOURNAL OF CLINICAL ONCOLOGY A R T O F O N C O L O G Y VOLUME 32 NUMBER 30 OCTOBER 2

Problems, progress and prognosis in trade and investment negotiations: the transatlantic free trade and investment partnership

A comprehensive Transatlantic Trade and Investment Partnership (TTIP) would increase economic output, create jobs, establish regulatory standards with global reach and set a new ‘gold standard’ for other trade agreements. However, institutionalised differences in key policy areas, divergent preferences for what constitutes an acceptable agreement, and sceptical populations constitute insurmountable hurdles. Using empirical and theoretical arguments, this paper is both a prediction for the TTIP and a contribution to our understanding of when and why trade negotiations fail, while also highlighting the positive side effects of negotiations. Assessing the extent to which the factors presented in this paper are present in other negotiations improves our understanding of the outcome of complex bilateral negotiations.

What a Difference a Year Makes: The International Court of Justice's 2012 Jurisprudence

An analysis of any particular decision of the International Court of Justice sometimes misses broader, cross-cutting themes that animate the Court’s jurisprudence. This essay, prepared for an April 2013 symposium at the European University Institute, Robert Schuman Centre for Advanced Studies, in Florence, explores a few of the themes that emerged from the Court’s 2012 jurisprudence. First, notwithstanding the development of treaty regimes across a broad array of international law, there remains an enduring relevance of customary international law and general principles of law as sources of international law. Second, when identifying rules of customary international law, there is an enduring attraction to analyzing the effects of multilateral treaties in codifying or crystalizing customary rules, rather than relying on a classic analysis of the day-to-day practice of States in conjunction with their opinio juris. Third, the concept of jus cogens remains a powerful feature of international law, available in theory to trump a State’s ability to engage in contrary treaties, yet in practice the concept seems to get little traction; certainly, violations of jus cogens have proven unable to open the door to claims before national and international tribunals. Finally, international law has increasingly become attuned to the rights of persons as against the power of States and international organizations, but the traditional processes of international law pose difficult and sometimes insurmountable hurdles to persons in effectively vindicating those rights. The Court’s jurisprudence highlights areas of international law that are incomplete or unsatisfactory. The ICJ’s role is not to legislate solutions in those areas, but the Court’s decisions point the direction for changes that might be pursued, either through the development of new treaties or institutions or improvements to those that already exist. Consequently, this essay concludes by suggesting some implications for the future codification and progressive development of international law.

Timely Completion of Scientifically Rigorous Cancer Clinical Trials: An Unfulfilled Priority

Timely Completion of Scientifically Rigorous Cancer Clinical Trials: An Unfulfilled Priority

Designing Opioids That Deter Abuse

Prescription opioid formulations designed to resist or deter abuse are an important step in reducing opioid abuse. In creating these new formulations, the paradigm of drug development target should be introduced. Biological targets relating to the nature of addiction may pose insurmountable hurdles based on our current knowledge and technology, but products that use behavioral targets seem logical and feasible. The population of opioid abusers is large and diverse so behavioral targets are more challenging than they appear at first glance. Furthermore, we need to find ways to correlate behavioral observations of drug liking to actual use and abuse patterns. This may involve revisiting some pharmacodynamic concepts in light of drug effect rather than peak concentration. In this paper we present several new opioid analgesic agents designed to resist or deter abuse using physical barriers, the inclusion of an opioid agonist or antagonist, an aversive agent, and a prodrug formulation. Further, this paper also provides insight into the challenges facing drug discovery in this field. Designing and screening for opioids intended to resist or deter abuse is an important step to meet the public health challenge of burgeoning prescription opioid abuse.

A Nuclear-Free Middle East – Just Not in the Cards

A scheduled conference to promote a zone free of weapons of mass destruction in the Middle East has renewed hopes for nuclear disarmament in this unstable region, if only innovative diplomacy could take advantage of the current shifts. However, a realistic assessment suggests that optimism is unwarranted. Fundamental strategic considerations related to Iran's nuclear program, Israel's atomic options, and the region's ingrate security architecture remain nearly insurmountable hurdles. Therefore, policymakers should focus first on attaining a resolution of the Israeli-Palestinian conflict.

Epistemic Evaluation of Religious Claims in Public Schools: A Response to Suzanne Rosenblith

The position the authors challenge in this article, one most notably advocated by Suzanne Rosenblith, suggests that religious study has a legitimate place in public education if and only if teachers and students grapple with the epistemic superiority of competing theistic claims. In this rejoinder, the authors propose that Rosenblith's suggestion faces 3 insurmountable hurdles to become an achievable education objective: (1) Rosenblith fails to articulate how religious claims might be evaluated epistemologically. Instead, she candidly admits there are presently no “clearly identifiable standards by which to measure religious and moral claims.” (2) In the absence of “clearly identifiable standards” to evaluate religious truth claims an untenable situation is created for schools, parents, students and teachers. Rosenblith's attempt to evaluate competing religious claims may foster increased conflict between different religious traditions. (3) The foundation, or “wider context,” required to support religious truth claims is itself epistemologically problematic.