bluuebunny/crossref_metadata_2025 huggingface dataset:
Making Complementarity a Reality
Authors: Brammertz Serge
Published: July 2020

This chapter presents a prosecutorial perspective on the International Criminal Tribunal for the former Yugoslavia’s (ICTY) legacies. It traces the evolution of the Office of the Prosecutor from a service that is grounded in primacy of jurisdiction into a more complementarity-oriented actor, in which interaction with domestic systems is an essential element to achieving justice for serious international crimes. The author argues that the support provided to national justice sectors in the countries of the former Yugoslavia is one of the most important legacies of the ICTY. The Office of the Prosecutor (OTP) started to engage with new techniques—including establishing the Transition Team—when the ICTY Completion Strategy was put into force. The OTP referred cases to national judiciaries, which improved in their capacities to process war crimes cases. The chapter concludes that the OTP’s cooperation with national courts establishes a new model of collaboration between international and domestic courts.
The ICTY and the Defence Legacy
Authors: Rohan Colleen
Published: July 2020

The chapter presents a defence perspective on the legacy of the International Criminal Tribunal for the former Yugoslavia (ICTY). The role of the Defence was initially sidelined in institutional discussions on the tribunal. This chapter traces the creation, functioning, and activities of the Association of Defence Counsel Practising Before the ICTY (ADC-ICTY). It outlines the ADC-ICTY contributions to the institutional legacy of the ICTY in organizing, training, and representing defence counsel thereby improving legal practice and protecting the rights of the accused.
Meandering Jurisprudence and Unanticipated Legacies
Authors: Drumbl Mark
Published: July 2020

Assessments of the International Criminal Tribunal for the former Yugoslavia’s (ICTY) jurisprudential legacy tend to focus on the ICTY’s relationships with domestic criminal law. This chapter turns a new corner by examining the ICTY’s unexpected footprints in domestic civil litigation, specifically private tort claims brought in the US under the Alien Tort Statute (ATS, or Alien Tort Claims Act). Incorporation of international (including ICTY) materials in US ATS litigation remains a contested matter in which individual judges (both trial judges and appellate judges) demonstrate idiosyncratic behaviour. Some are ‘international law ignorers’, some are ‘international law enforcers’, some are ‘international law translators’, and some are ‘international law creators’. On this note, the ICTY’s legacy also touches upon broader questions of public international law and transnational legal migrations.
Lessons Learned from the Use of DNA Evidence in Srebrenica-related Trials at the ICTY
Authors: Vanderpuye Kweku , Mitchell Christopher
Published: July 2020

This chapter discusses legal issues associated with the collection, storage, and use of DNA evidence in international and national criminal trials. It draws on experience at the International Criminal Tribunal for the former Yugoslavia (ICTY) in the Srebrenica cases. It shows how DNA evidence was used to identify the number of victims in a mass grave, and links and patterns between a victim and one or more crime sites. The chapter argues that the probative value and admissibility of DNA evidence is maximized when used in conjunction with other forensic sciences (e.g. archaeology, pathology, and anthropology). Also that reliance on all forensic sciences, not just DNA analysis, is the most likely way of establishing a complete picture of the victim’s identity; as well as the cause, manner, and circumstances of the victim’s death.
Translating and Interpreting at the ICTY
Authors: Elias-Bursać Ellen
Published: July 2020

Procedures developed at the International Criminal Tribunal for the former Yugoslavia (ICTY) in response to issues concerning evidence translation and testimony interpretation have provided international criminal courts and tribunals with expertise and insight. These will shape the profession for decades to come. As to the impact on jurisprudence, the Conference and Language Service Section (CLSS), being part of Registry, played a key—often underestimated—role in ensuring the equality of arms between the parties. In a larger sense, the provisional nature of translated texts and interpreted testimony encourages challenges and disputes, and these discussions move the proceedings to a greater understanding; precisely because the obstacles presented by dealing with other languages and cultures force everyone in the courtroom to pay more attention to communication and meaning. It is this constant querying of what everyone thought they did or did not understand that takes these complex trials to completion and comprehension.
Punishing for Humanity
Authors: deGuzman Margaret M.
Published: July 2020

In determining sentences, the ICTY chose to develop global norms rather than adhere to, or even be strongly guided by, the sentencing norms of the former Yugoslavia. Although the ICTY Statute required the judges to consult national practices in determining sentences, they interpreted this requirement loosely, reserving to themselves a wide discretion that enabled them to identify a range of global sentencing objectives and factors to apply in pursuit of those objectives. The global norms the ICTY developed included norms rejecting harsh punishment, applying consequentialist punishment rationales, privileging gravity as the central sentencing factor, and endorsing broad judicial sentencing discretion. In developing these norms, the ICTY helped to build a foundation that other international courts, and perhaps some national courts, are likely to rely on for the foreseeable future.
Croatia’s Homeland War, the Battles Over Victor’s Justice, and the Legacy of the ICTY
Authors: Peskin Victor
Published: July 2020

The creation of the International Criminal Tribunal for the former Yugoslavia (ICTY) marked the affirmation and negation of the Nuremberg Tribunal's legacy. The ICTY had been given a mandate to continue in the legal footsteps of Nuremberg by prosecuting egregious violations of International Humanitarian Law (IHL). But the ICTY also established a lasting legacy all of its own by seeking to prosecute suspects from all combatant groups in the former Yugoslavia, including the victorious sides. The aim of this chapter is to twofold: (1) to assess how well the ICTY confronted the spectre of victor’s justice in the context of the Croatia case and (2) to examine the strategies the Tribunal and allied states used to overcome Croatian state non-compliance..
The Broken Path to Reconciliation in Bosnia and Herzegovina
Authors: Aloisi Rosa
Published: July 2020

The International Criminal Tribunal for the former Yugoslavia (ICTY) has delivered judgments adjudicating some of the most heinous crimes committed in the Balkans. As the Tribunal’s work comes to an end, judges leave behind a ‘memorial of words’ providing a vivid description of events and sites of atrocities. However, today local authorities in Bosnia and Herzegovina (BiH) use the same places where crimes were committed as a political tool of denial and battleground of ethnic divisions. This chapter assesses the tensions between the truth recounted by the ICTY and the construction of the local collective memory through an analysis of how the sites of atrocities are being used. This chapter argues that, while international justice offers some resolution to a post-war divided society, a full reconciliation is only possible when the communities acknowledge the occurrence of atrocities and the right of victims to visit these places to mourn and remember.
The ICTY, Truth, and Reconciliation
Authors: Clark Janine Natalya
Published: July 2020

Exploring the question of whether the International Criminal Tribunal for the former Yugoslavia’s (ICTY) work has contributed to inter-ethnic reconciliation in the former Yugoslavia, this inter-disciplinary chapter adopts a novel perspective by extending the purview beyond factual truths. It focuses on meta-normative truths. These higher-level truths are not about who did what to whom, but about human suffering and the (im)morality of particular behaviours and conduct in war. Precisely because they transcend ethnic belonging, these truths provide a stronger basis for building reconciliation than frequently-contentious factual truths. The chapter maintains that meta-normative truths have the greatest potential to alter localized meta-affective contexts that fuel denial, support for convicted war criminals and the persistence of competing ethnic narratives. Although the Tribunal has now completed its mandate, it can indirectly contribute to inter-ethnic reconciliation if the meta-normative truths implicit in its work are given more attention and actively utilized in reconciliation efforts.
Human Rights Unbound
Authors: Raible Lea
Published: July 2020

This book develops a theory of extraterritorial human rights obligations in international law. It links debates on human rights theory with those relating to extraterritoriality and merges accounts of economic social and cultural rights with those of civil and political rights. It advances four main arguments aimed at changing the way we think about extraterritoriality of human rights. First, it is argued that the questions regarding extraterritoriality are really about justifying the allocation of human rights obligations to specific states. Second, the book shows that human rights as found in international human rights treaties are underpinned by the values of integrity and equality. Third, it is argued that these same values justify the allocation of human rights obligations towards specific individuals to public institutions—including states—that hold political power over said individuals. And fourth, the book argues that title to territory is best captured by the value of stability, as opposed to integrity and equality. If these arguments are successful, their consequence is a major shift in how we view extraterritorial human rights obligations. Namely, the upshot is that all standards in international human rights treaties that count as human rights require that a threshold of jurisdiction, understood as political power, is met. However, on the present account, this threshold is not just a conceptual necessity but a normative one as well. It is needed because it not only describes, but also justifies the allocation of obligations.
Introduction
Authors: Raible Lea
Published: July 2020

The introduction begins by setting out puzzles that any account of extraterritorial human rights obligations would need to address. These puzzles are meant to illustrate that economic and social rights bring to the fore two of the most foundational issues of international human rights law more broadly. These are, namely, what it means for a state to have a human rights obligation towards an individual, and how we justify the specification of the relevant right holder and duty bearer in each case. A clear textual basis or even a starting point is lacking in international law. Making reference to economic and social rights forces us to frame extraterritoriality as a question of identifying right holders and duty bearers. In turn, answering this question allows us to challenge conventional wisdom on extraterritoriality in general. The Introduction sets out the method, theoretical background, and aims of this book, outlining the arguments based on the analysis of legal practice and scholarly literature, and their implications.
Norm Expression
Authors: Stahn Carsten
Published: July 2020

Expressivist theory suggests that international criminal justice can serve as a means to instil norms and values in international society through communicative justice and persuasion. The chapter demonstrates that contemporary practice shifts between norm expression and norm entrepreneurship. It relates norm expression to the imperfect structure of international law and the performative nature of crimes. It argues that norm expression is partially a counter-performance to crimes. It shows that international criminal justice has captured new space and forms of social behaviour through thematic investigations and prosecutions (e.g. sexual and gender-based violence, child soldiers, cultural property) and legal practice relating to core crimes. It illustrates how legal agents have used rhetoric techniques (e.g. narration, storytelling, and imagery) to reformulate some of the premises of underlying bodies of law (e.g. human rights law, international humanitarian law, and the law of the use of force).
The Stoics
Authors: Irwin Terence
Published: July 2020

The Stoics argue for two apparently conflicting claims: (1) Virtue is sufficient for happiness, because it is the whole of happiness. Hence Plato and Aristotle are wrong. (2) Goods apart from virtue (as Plato and Aristotle conceive them)—health, wealth, good fortune—are preferred indifferents; they deserve rational concern even though they are not goods and contribute nothing to happiness. Hence the Cynics are wrong. The human soul has no non-rational desires; passions are not non-rational conditions, but are simply false beliefs that different sorts of preferred and non-preferred indifferents are really good and evil. Reason controls not only human life, but the providential ordering of the cosmos as a whole. This providential ordering does not undermine human freedom and responsibility. Contrary to Epicurus’ views, predetermination of our actions still allows us to act freely and to be responsible for our actions.
Christian Belief and Moral Philosophy
Authors: Irwin Terence
Published: July 2020

Christian literature, from the New Testament onwards, pursues the main themes of ancient ethics, from the theological perspective derived from the Old Testament. Both Jewish and Christian writers defend their moral views by appeal to the natural law and natural reason that the Stoics acknowledge. The Christian Gospel does not reveal the moral law, but (1) makes us aware of how demanding it is, (2) shows us that we cannot fulfil its demands by our own unaided efforts, and (3) reveals that we can keep it through divine help that turns our free will in the right direction. These three claims underlie the Pauline and Augustinian doctrines of divine grace and human free will. Christian ethics looks forward to the ‘City of God’, which cannot be realized in human history. But it also engages with human societies in order to carry out the demands of the moral law.
Scotus and Ockham
Authors: Irwin Terence
Published: July 2020

Scotus and Ockham reject the Aristotelian outlook, as Aquinas presents it, and develop a voluntarist account of the will and of morality. In their view, determination by practical reason does not ensure free will; a free will must be wholly undetermined by reason. Nor can it be determined by the desire for one’s ultimate good; the impulse towards the right is separate from the impulse towards happiness. If we apply these principles to the freedom of the divine will, we find that God could not be free if the nature of right and wrong were independent of the divine will. We must infer that moral rightness and wrongness are ultimately constituted by divine commands.
Utilitarianism and Its Critics
Authors: Irwin Terence
Published: July 2020

Later defences of utilitarianism, by Lewis and Hare, support Sidgwick’s claim that the utilitarian outlook is the outlook of practical reason. They argue that the appropriate extension of sympathy requires imaginative identification with the pleasures and pains of other people, in a way that leads to the utilitarian attitude. Ross, however, argues that utilitarianism gives us neither a correct account of moral concepts nor a correct account of moral properties. When we consider what makes right actions right, we have good reason to agree with Price in rejecting utility as the supreme principle of morality. Rawls defends this argument against utilitarianism. To decide what our considered moral judgments commit us to, we describe fair conditions in which we can choose between different principles of justice. In these fair conditions we accept principles that conflict with utilitarianism, but conform to Kant’s principle of respect for persons as ends.
Prevalence and correlates of multiple behavioural risk factors of non-communicable diseases among university students from 24 countries
Authors: Pengpid Supa , Peltzer Karl
Published: July 2020

Background

Globally non-communicable diseases (NCDs) are on the increase. The goal of the study was to estimate the prevalence and correlates of multiple behavioural risk factors of NCDs among university students from 24 countries.

Methods

In a cross-sectional study, the sample included 18 017 university students from countries in Africa, the Americas and Asia.

Results

indicate that prevalence of single behavioural NCD risk indicators were 38.2% for physical inactivity, 80.5% for inadequate fruit and vegetables intake, 23.1% for having overweight/obesity, 10.5% for heavy alcohol use and 11.8% for current tobacco use. Students had on average 1.6 (SD = 0.9), and 15.9% had three or more behavioural NCD risk factors. In adjusted linear regression, male sex was positively and stronger beliefs in health benefits were negatively associated with multiple behavioural NCD risk factors.

Conclusions

A high prevalence and co-occurrence of behavioural risk factors of NCDs was discovered. Several behavioural NCD risk factors, such as male sex and low health behaviour benefits beliefs, were found that could be utilized in targeted interventions.
Variations in newspaper reporting of suicidal behavior in the WHO–South-East Asian region
Authors: Arafat S M Yasir , Menon Vikas , Bascarane Sharmi , Kar Sujita Kumar , Kabir Russell
Published: July 2020

Background

South-East Asia is a densely populated region, comprising of 11 low- and middle-income countries and contributing to 39% of global suicides. There are serious challenges to suicide prevention in the region such as lack of high-quality suicide data, underreporting and poor quality of media reporting. The current report aimed to assess the variations in newspaper reporting of suicidal behavior in the World Health Organization–South-East Asian countries.

Methods

We analyzed the contents of nine research articles on media reporting of suicide, published from four South-East Asian countries (four from Bangladesh, three from India, one each from Indonesia and Bhutan) that used similar methods and presented results in a nearly similar fashion.

Results

Personal identifying information of the deceased was very frequently mentioned in the newspaper reports across the countries. Suicide notes were reported more commonly in India (9.5–18%) than Bangladesh (4.2–7.5%) and Indonesia (9.5%). No educative material was found in any of the newspaper reports of Bangladesh and Indonesia while it was rarely reported in Bhutan and India.

Conclusion

Our findings from the four South-East Asian countries suggest that there are variations between the countries while presenting the news reports of suicidal behavior. These findings would help to formulate and regulate the media guidelines for the specific country.
‘You Don't Have Any Business Being This Good’: An Oral History Interview with Bernardine Lacey
Authors: Lewenson Sandra B. , Graham-Perel Ashley
Published: July 2020

Racism left an indelible mark on Bernardine Lacey and her professional growth as a nurse, including roles as an educator, political advocate, researcher, clinician, and leader. This article uses oral history methods to detail, in Lacey's own words, experiences from her childhood and early in her education and career. Her story allows for an exploration of some of the difficult truths about racism, the culpable role of nursing in this history, and the impact of historical accounts on the profession's current inclusivity and diversity efforts.
Investing in Nursing's Future
Authors: Hewlett Peggy O'Neill , Santolla Jan , Persaud Sabita Devi
Published: July 2020

Nursing leaders continue to struggle with capacity issues in both clinical and academic settings—particularly those related to aging patient and nurse populations and the increasing complexity of health care in general. Programs and resources for formal mentoring have primarily focused on mid- and advanced-career RNs, but there is an imperative to develop methods of expertly mentoring “professionally younger” RNs across all settings and roles. In 2017, the American Nurses Association (ANA) conducted an extensive member needs assessment with more than 15,000 respondents. Three distinct career-stage categories were identified: early-career nurses, up-and-comers, and nursing leaders. The early-career nurses and up-and-comers listed “being mentored” among their top two member benefit requests. In response, the ANA launched a national virtual mentorship program in September 2018. The program aligned with criteria, recommendations, and charges from the American Nurses Credentialing Center's 2019 Magnet Recognition Program; the landmark 2010 report from the Institute of Medicine (IOM), The Future of Nursing: Leading Change, Advancing Health; and a 2019 IOM consensus study, The Future of Nursing 2020-2030. This article provides a general overview of the program, including evaluation and modifications, and discusses implications of using the ANA's career-stage categories in virtual mentoring.
Efficacy of Pulsed Radiofrequency in Herpetic Neuralgia
Authors: Wu Chih-Yin , Lin Heng-Ching , Chen Shu-Fen , Chang Wen-Pei , Wang Chia-Hui , Tsai Jui-Chen , Lin Ying-Chin , Kao Yuan , Tam Ka-Wai
Published: July 2020

Objectives:

Herpes zoster and postherpetic neuralgia (PHN) are often refractory to current standard treatments and can reduce patients’ quality of life (QoL). Pulsed radiofrequency (PRF) effectively controls intractable neurological pain. The aim of the study was to conduct a systematic review and meta-analysis to evaluate the efficacy of PRF in PHN management.

Materials and Methods:

We searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) published up to October 2019. The primary outcomes were pain levels and rescue analgesia at different postintervention time intervals. The secondary outcomes were QoL and sleep quality.

Results:

We reviewed 6 RCTs involving 420 patients. The meta-analysis revealed that the PRF group exhibited significantly lower pain scores in PHN than did the control group at 2 to 3 days (weighted mean differences [WMD]=−2.82; 95% confidence interval [CI]: −5.08 to −0.55), 1 week (WMD=−2.95; 95% CI: −4.53 to −1.37), 2 weeks (WMD=−3.17; 95% CI: −4.11 to −2.23), 4 weeks (WMD=−2.59; 95% CI: −3.40 to −1.79), 8 weeks (WMD=−3.02; 95% CI: −4.17 to −1.88), and 6 months (WMD=−1.94; 95% CI: −2.85 to −1.03). After intervention, QoL was significantly higher in the PRF group than in the control group. No major complications were reported.

Discussion:

PRF safely and effectively reduced pain scores and improved QoL in patients with herpes zoster in the cervical to lumbosacral areas. PRF could be considered during refractory PHN treatment. Future studies require standardized PRF settings and outcome assessment tools, including physical and emotional function assessments.
Test-Retest Reliability of the Dizziness Symptom Profile
Authors: Landon-Lane Renee L. , Piker Erin G. , Jacobson Gary P. , Hatton Kelsey , Roberts Richard A.
Published: July 2020

Objectives:

This investigation was conducted to measure the test-retest reliability of the Dizziness Symptom Profile (DSP). The DSP was developed to assist primary care providers, general otolaryngologists, and other health care providers in the development of a differential diagnosis for patients who present with dizziness, vertigo, or unsteadiness. The DSP yields a score ranging from 0 to 100% for each of 7 subscales. Each subscale represents a different diagnosis including benign paroxysmal positional vertigo, Ménière’s disease, persistent postural-perceptual dizziness (PPPD), superior semi-circular canal dehiscence, vestibular migraine, vestibular neuritis, and general unsteadiness.

Design:

Subjects were 150 adult patients (mean age 56.79 years, SD 15.69 years) referred to the Balance Disorders Clinic at Vanderbilt University Medical Center. Subjects completed two administrations of the DSP. The mean interval between test administrations was 1.58 days (SD 1.78 days). The response modes for the DSP were both a 0 to 100 mm visual analog scale (scored 0 mm = “strongly disagree” to 100 mm = “strongly agree”) and, by extrapolation, the original 5-point Likert scale where the anchors were “strongly disagree” (scored 0 points) and “strongly agree” (scored 4 points).

Results:

Pearson correlation coefficients were calculated to assess test-retest reliability for individual DSP items, and ranged from r = 0.67 to 0.91 (mean 0.80; p < 0.001). Cronbach’s α coefficients were calculated to assess internal consistency reliability of items comprising the seven subscales. Each subscale had an acceptable level of internal consistency (Cronbach’s α coefficients > 0.7) with the exception of PPPD which approached 0.7. Intraclass correlation coefficient estimates and their 95% confidence intervals were also calculated to assess the relative reliability of the subscales. All 7 subscales showed moderate to strong test-retest reliability, with intraclass correlation coefficients ranging from 0.85 to 0.94. Minimal detectable change (MDC) scores were calculated to assess absolute variability/measurement error for the seven subscale scores (which range from 0 to 100%). MDC values ranged from 16% (PPPD) to 25% (unsteadiness).

Conclusions:

(1) The test-retest reliability of the DSP is moderate to strong. (2) MDC values for each subscale were determined. (3) The DSP coupled with the Dizziness Handicap Inventory enables the clinician to evaluate the constructs of dizziness impairment, and disability/handicap. (4) The DSP may help provide a window to the natural history of dizziness disease(s). (5) The DSP provides a less biased assessment of the symptoms reported by the patient.
Gamma-decanolactone attenuates acute and chronic seizures in mice: a possible role of adenosine A1 receptors
Authors: Pflüger Pricila , Regner Gabriela Gregory , Luft Jordana Griebler , Gonçalves Débora Aguirre , Krebs Chris , Fontenla José Angel , Pereira Patrícia
Published: July 2020

This study aimed to investigate the possible gamma-decanolactone mechanisms of action in the GABAergic and adenosine systems using the aminophylline-induced acute crisis model and the pentylenetetrazole-induced kindling model. In the acute model, male mice received administration of bicuculline (GABAA receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (A1 receptor antagonist) or ZM241385 (A2A receptor antagonist), 15 min before the treatment with gamma-decanolactone (300 mg/kg). After a single dose of aminophylline was administered, the animals were observed for 60 min. In the chronic model of seizure, 30 min after the treatment with gamma-decanolactone, mice received pentylenetetrazole once every third day. On the last day of kindling, the animals received the same GABA and adenosine antagonists used in the acute model, 15 min before gamma-decanolactone administration. The protein expression of GABAA α1 receptor and adenosine A1 receptor was detected using western blotting technique in hippocampal samples. The results showed that gamma-decanolactone increased the latency to first seizure and decreased seizure occurrence in the acute and chronic models. The adenosine A2A receptor antagonist and GABAA receptor antagonist were not able to change gamma-decanolactone behavioral seizure induced by aminophylline or pentylenetetrazole. The administration of adenosine A1 receptor antagonist reversed the protective effect of gamma-decanolactone in both models. In addition, gamma-decanolactone promoted an increase in the expression GABAA α1 receptor, in the hippocampus. The results suggest that the neuroprotective effect of gamma-decanolactone observed during the investigation could have a straight connection to its action on A1 adenosine receptors.
5-Fluorouracil Response Prediction and Blood Level–Guided Therapy in Oncology: Existing Evidence Fundamentally Supports Instigation
Authors: Chavani Ottiniel
Published: July 2020

5-Fluorouracil (5-FU) response prediction and therapeutic drug monitoring (TDM) are required to minimize toxicity while preserving efficacy. Conventional 5-FU dose normalization uses body surface area. It is characterized by up to 100-fold interindividual variability of pharmacokinetic (PK) parameters, and typically >50% of patients have plasma 5-FU concentrations outside the optimal range. This underscores the need for a different dose rationalization paradigm, hence there is a case for 5-FU TDM. An association between 5-FU PK parameters and efficacy/toxicity has been established. It is believed that 5-FU response is enhanced and toxicity is reduced by PK management of its dosing. The area under the concentration–time curve is the most relevant PK parameter associated with 5-FU efficacy/toxicity, and optimal therapeutic windows have been proposed. Currently, there is no universally applied a priori test for predicting 5-FU response and identifying individuals with an elevated risk of toxicity. The following two-step strategy: prediction of response/toxicity and TDM for subsequent doses seems plausible. Approximately 80% of 5-FU is degraded in a three-step sequential metabolic pathway. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme. Its deficiency can cause toxicity with standard 5-FU doses. DPD also metabolizes uracil (U) into 5,6-dihydrouracil (UH2). The UH2/U ratio is an index of DPD activity and a credible biomarker of response and toxicity. This article outlines the UH2/U ratio as a parameter for 5-FU response/toxicity prediction and highlights key studies emphasizing the value of 5-FU TDM. Broad application of 5-FU response/toxicity prediction and blood level–guided therapy remains unmet, despite ever-increasing clinical interest. Considered collectively, existing evidence is compelling and fundamentally supports universal instigation of response/toxicity prediction and TDM.
Salting Out-Assisted Liquid–Liquid Extraction for Liquid Chromatography–Tandem Mass Spectrometry Measurement of Tacrolimus, Sirolimus, Everolimus, and Cyclosporine a in Whole Blood
Authors: Kvamsøe Marianne M. , Hansen Kristina R. , Skadberg Øyvind , Vethe Nils T. , Brede Cato
Published: July 2020

Background:

Therapeutic drug monitoring of the immunosuppressants tacrolimus, sirolimus, everolimus, and cyclosporine A is effectively performed by analyzing whole-blood samples using liquid chromatography coupled with tandem mass spectrometry. Samples are usually prepared using simple protein precipitation (PPT) with methanol and zinc sulfate (ZnSO4). Significant sample dilution is necessary to obtain clean extracts but may increase the limit of quantification of the method. Salting out–assisted liquid–liquid extraction (SALLE) was explored as a novel sample preparation method for measuring these drugs in blood.

Method:

SALLE, which simply consists of LLE with a water-miscible solvent where phase separation is achieved by adding salt, was used to analyze treated blood samples.

Results:

SALLE allowed direct injection of a 5-µL extract from the upper solvent phase into a reversed phase LC column, which would not be feasible using standard LLE. Compared with PPT, SALLE provided better extraction efficiencies and more ion enhancement, resulting in limit of quantification of 0.4, 1.4, 0.06, and 0.4 ng/mL for tacrolimus, sirolimus, everolimus, and cyclosporine A, respectively. Full-method validation was performed, including a comparison of results with those of another laboratory. A ≤10% bias was observed for tacrolimus and cyclosporine A, whereas further investigation of that for sirolimus (−12%) and everolimus (−18%) revealed that it was caused by the different calibrators used.

Conclusions:

This is the first report of the use of SALLE for the measurement of tacrolimus, sirolimus, everolimus, and cyclosporine A in whole blood. The advantages of SALLE over PPT and conventional LLE would make it an attractive sample preparation method for clinical laboratories.
Environmental Influences and Polycystic Ovarian Syndrome
Authors: DUNN ARIEL J.
Published: July 2020

Polycystic ovarian syndrome (PCOS) is a complex endocrine-metabolic disorder whose pathogenesis is not well-understood. While genetic insults have been hypothesized as possible causes, there are a large number of environmental chemicals known to have detrimental effects on the endocrine system and may be irreversible, especially when exposure occurs early in development. Many of these chemicals have been investigated as causes of PCOS by measuring serum and urinary levels of common endocrine disruptors in women and adolescents with PCOS as well as using animal models for PCOS induction with chemical exposures.
RETINAL DETACHMENT WITH INFERIOR RETINAL BREAKS
Authors: Starr Matthew R. , Obeid Anthony , Ryan Edwin H. , Ryan Claire , Ammar Michael , Patel Luv G. , Forbes Nora J. , Capone Antonio , Emerson Geoffrey G. , Joseph Daniel P. , Eliott Dean , Gupta Omesh P. , Regillo Carl D. , Hsu Jason , Yonekawa Yoshihiro ,   For the Primary Retinal Detachment Outcomes (PRO) Study Group
Published: July 2020

Introduction:

Rhegmatogenous retinal detachments with inferior retinal breaks are believed to have a higher risk of recurrent rhegmatogenous retinal detachment. This study compared anatomic and visual outcomes between primary pars plana vitrectomy (PPV) and combination PPV with scleral buckle (PPV/SB) for rhegmatogenous retinal detachments with inferior retinal breaks.

Methods:

This is an analysis of the Primary Retinal Detachment Outcomes study, a multi-institutional cohort study of consecutive primary rhegmatogenous retinal detachment surgeries from January 1, 2015, through December 31, 2015. The primary outcome was single-surgery success rate. Only eyes with inferior retinal breaks (one break in the detached retina between five and seven o'clock) were included.

Results:

There were 238 eyes that met the inclusion criteria, 95 (40%) of which underwent primary PPV and 163 (60%) that underwent combined PPV/SB. The single-surgery success rate was 76.8% for PPV and 87.4% for PPV/SB (P = 0.0355). This remained significant on multivariate analysis (P = 0.01). Subgroup analysis showed that a superior single-surgery success rate of PPV/SB was especially noted in phakic eyes (85.2% vs. 68.6%; P = 0.0464).

Conclusion:

Retinal detachment with inferior retinal breaks had a higher single-surgery success rate if treated with PPV/SB compared with PPV alone, particularly in phakic eyes.
The Early Effects of Alcohol Consumption on Functional Visual Acuity, Tear Functions, and the Ocular Surface
Authors: Simsek Cem , Kojima Takashi , Dogru Murat , Tanaka Mari , Takano Yoji , Wakamatsu Tais , Ibrahim Osama , Toda Ikuko , Negishi Kazuno , Tsubota Kazuo
Published: July 2020

Purpose:

We investigated the early effects of alcohol intake on tear functions and ocular surface health in this prospective controlled study.

Methods:

Forty-four eyes of 22 subjects (17 males, 5 females; mean age: 35.3 years) who drank 200 mL of 25% Japanese vodka and 44 eyes of age- and sex-matched 22 control subjects who drank water were investigated. Subjects were requested to refrain from alcohol consumption from the previous day and food ingestion 6 hr before the study. Each subject consumed exactly the same order prepared dinner and same quantity of alcohol over the same time frame. Subjects underwent breath alcohol level, tear evaporation and blink rate, tear lipid layer interferometry, tear film break-up time (BUT), fluorescein and Rose Bengal stainings, Schirmer test, and visual analog scale (VAS) evaluation of dry eye symptoms before, as well as 2 and 12 hr after alcohol intake.

Results:

The mean breath alcohol level was significantly higher in the alcohol group compared to the water group at 2 and 12 hr (P<0.001). The mean tear evaporation increased significantly from 2.5×10−7 to 8.8×10−7 gr/cm2/sec 12 hr after alcohol intake (P<0.001). The mean BUT shortened significantly from 15.0±5.0 to 5.0±2.5 sec 12 hr after alcohol intake. Lipid layer interferometry showed signs of tear film thinning 12 hr after alcohol intake in all subjects of the alcohol intake group, which was not observed in the water group. The mean blink rates increased significantly from 10.6±1.5 blinks/min to 13.5±0.9 blinks/min and 15.1±1.2 blinks/min at 2 and 12 hr, respectively, in the alcohol group (P<0.001). The Schirmer test values decreased significantly 12 hr after alcohol intake (P<0.001). The mean VAS score for dryness increased from baseline significantly in the alcohol group at 12 hr (P<0.001). No significant time-wise changes in tear functions were observed in the water group.

Conclusion:

The tear film and ocular surface epithelia showed early and distinctive quantitative and qualitative changes associated with visual disturbances after alcohol intake.
Should Overnight Orthokeratology Patients Wear Their Lenses During Their Afternoon Nap?
Authors: Pérez-Corral Joan , Cardona Genis , Piñero David P. , Aradilla Yolanda , García Mireia
Published: July 2020

Purpose:

The purpose of this study was to evaluate changes in visual acuity, corneal curvature, elevation, pachymetry, and objective quality of vision of experienced orthokeratology patients using their contact lenses during a simulated 30-min afternoon nap.

Method:

Twelve patients aged 30.8±8.3 years were recruited for the study, with a history of overnight orthokeratology of 27.4±23.0 months. Patients were instructed to close their eyes for 30 min while wearing their contact lenses or without lenses. Anterior corneal curvature, elevation, and corneal pachymetry were assessed with the Pentacam Scheimpflug System at 17 predefined corneal locations, and the HD Analyzer (Terrassa, Spain) was used to measure objective quality of vision. Measurements were conducted before eye closure (baseline), immediately after eye opening/lens removal (M1), and 30 min later (M2).

Results:

No statistically significant differences were found in anterior corneal curvature and elevation between baseline values and M1 or M2, with and without contact lenses. Corneal swelling at M1 was greater without contact lenses (change in central corneal thickness of 2.3%±3.1%, P=0.001) than with contact lenses (1.7%±1.3%, P<0.001). Recovery at M2 was slower when lenses were worn. A statistically significant improvement in objective quality of vision and visual acuity was found only when patients napped with their lenses.

Conclusions:

Even if no significant changes were found in corneal curvature and elevation, patients of overnight orthokeratology may benefit from using their contact lenses during their afternoon nap in terms of objective quality of vision and visual acuity.
The predictive value of quantitative sensory testing: a systematic review on chronic postoperative pain and the analgesic effect of pharmacological therapies in patients with chronic pain
Authors: Petersen Kristian Kjær , Vaegter Henrik B. , Stubhaug Audun , Wolff André , Scammell Brigitte E. , Arendt-Nielsen Lars , Larsen Dennis B.
Published: July 2020

Studies have suggested that quantitative sensory testing (QST) might hold a predictive value for the development of chronic postoperative pain and the response to pharmacological interventions. This review systematically summarizes the current evidence on the predictive value of QST for chronic postoperative pain and the effect of pharmacological interventions. The main outcome measures were posttreatment pain intensity, pain relief, presence of moderate-to-severe postoperative pain, responders of 30% and 50% pain relief, or validated questionnaires on pain and disability. A systematic search of MEDLINE and EMBASE yielded 25 studies on surgical interventions and 11 on pharmacological interventions. Seventeen surgical and 11 pharmacological studies reported an association between preoperative or pretreatment QST and chronic postoperative pain or analgesic effect. The most commonly assessed QST modalities were pressure stimuli (17 studies), temporal summation of pain (TSP, 14 studies), and conditioned pain modulation (CPM, 16 studies). Of those, the dynamic QST parameters TSP (50%) and CPM (44%) were most frequently associated with chronic postoperative pain and analgesic effects. A large heterogeneity in methods for assessing TSP (n = 4) and CPM (n = 7) was found. Overall, most studies demonstrated low-to-moderate levels of risk of bias in study design, attrition, prognostic factors, outcome, and statistical analyses. This systematic review demonstrates that TSP and CPM show the most consistent predictive values for chronic postoperative pain and analgesic effect, but the heterogeneous methodologies reduce the generalizability and hence call for methodological guidelines.
Association between Visceral Adiposity Index and hypertension among Chinese Adults: a nationwide cross-sectional study in the China Health and Nutrition Survey
Authors: Yang Jing , Li Hongxia , Han Lianhua , Zhang Lei , Zhou Yafeng
Published: July 2020

Background

Visceral Adiposity Index (VAI) is an indicator of visceral adipose function. It showed an intense association with cardiometabolic risks, but it is unclear whether VAI is associated with hypertension.

Objective

We aim to determine the association of VAI with hypertension in Chinese adults.

Methods

We carried out a cross-sectional analysis of 5421 Chinese adults based on data which was from the China Health and Nutrition Survey (CHNS) 2009. Multivariable logistic regression and linear regression were performed to confirm the association.

Results

In multivariable logistic regression analysis, there was a dose-response association between VAI and the risk of incident hypertension (P for trend <0.01). The sex and age-adjusted odds ratios (ORs) [95% confidence interval (CI)] for the development of hypertension were 1.06 (0.90–1.26) in the second, 1.09 (0.92–1.29) in the third, and 1.28 (1.08–1.52) in the fourth VAI quartile, compared to the first quartile. The multivariable linear regression analysis indicated that VAI was positive association with systolic blood pressure (β = 0.37; 95% CI, 0.13–0.62; P = 0.0028) and diastolic blood pressure (β = 0.26; 95% CI, 0.12–0.40; P = 0.0004). The subgroup analysis showed that VAI had more positive association with hypertension in participants with an apolipoprotein A1 of ≥1.2 g/L (P = 0.0115) or a hemoglobin A1c of ≥6.5% (P = 0.0369).

Conclusions

VAI was positively associated with hypertension among the Chinese adult population, and it may assume an indicator of hypertension risk for the Chinese population.
Frailty in patients with interstitial lung disease
Authors: Guler Sabina A. , Ryerson Christopher J.
Published: July 2020

Purpose of review

The incidence of age-related diseases such as interstitial lung disease (ILD) is rising, and the importance of multimorbidity and accumulation of health deficits in patients with chronic lung diseases is increasingly recognized. There are multiple relationships between aging and ILD on a demographic and a biological level. Frailty conceptualizes the decline of a patient's physiological reserves and complements the chronological and biological aspects of aging.

Recent findings

Frailty affects more than 50% of patients with ILD, with respiratory impairment, accelerated biological aging, comorbidities, medication adverse effects, and social factors collectively playing important roles. Frailty is an independent risk factor for adverse health outcomes such as hospitalizations and early mortality, including before and after lung transplant. Given the multicomponent determinants of frailty, programs such as pulmonary rehabilitation are promising strategies for managing this complex issue.

Frailty is a common risk factor for adverse outcomes in patients with ILD. The multiple pathways leading to frailty are not completely understood, and further studies are needed to determine the optimal tools for assessment and to develop strategies to prevent and counteract frailty in the aging ILD population.
Pulmonary hypertension in majority countries: opportunities amidst challenges
Authors: Maarman Gerald J. , Shaw Jane , Allwood Brian
Published: July 2020

Purpose of review

Pulmonary hypertension is a deadly disease, the causes of which vary between geographical regions. Eighty four percentage of the world's population lives in majority countries (also called low-income and middle-income countries), yet data on pulmonary hypertension in these settings are proportionally scarce. This article provides a review of pulmonary hypertension in majority countries, focusing in detail on the most common causes in these regions, and highlights contextual challenges faced.

Recent findings

Epidemiological data confirms a complex and overlapping array of causes, with pulmonary hypertension because of conditions such as rheumatic heart disease, HIV, schistosomiasis, chronic lung disease and sickle cell disease. Delayed pulmonary hypertension diagnosis remains a concern and is ascribed to a lack of resources and lack of pulmonary hypertension awareness by health professionals. Pulmonary hypertension diagnosis is frequently considered once signs of right heart failure emerge, while echocardiography and right heart catheterization are unavailable in many settings. Accurate data on the prevalence of pulmonary hypertension in many of these regions are needed and could be achieved by establishing and frequent review of national databases where the incident and prevalent pulmonary hypertension cases are captured.

There is urgent need for pulmonary hypertension advocacy among clinicians in the primary, secondary and tertiary healthcare sectors of majority countries, and validated noninvasive diagnostic algorithms are needed. Increased awareness and early diagnosis are likely to improve outcomes of pulmonary hypertension patients in these regions, and potentially stimulate locally relevant research.
Advances in exercise therapy in predialysis chronic kidney disease, hemodialysis, peritoneal dialysis, and kidney transplantation
Authors: Wilkinson Thomas J. , McAdams-DeMarco Mara , Bennett Paul N. , Wilund Kenneth
Published: July 2020

Purpose of review

Chronic kidney disease (CKD) is characterized by poor levels of physical activity which contribute to increased morbidity across the disease trajectory. The short nature, small samples, and poor methodology across most studies have failed to translate the role of exercise in CKD into its adoption as a frontline adjunct therapeutic option. This review focuses on recent advances surrounding the benefits of exercise interventions across the CKD spectrum.

Recent findings

Key recent advances in exercise studies have focused on the efficacy of novel intervention strategies across the CKD spectrum. These include high-intensity interval training, virtual reality gaming, intradialytic yoga, electrical stimulation of muscles, blood flow restriction training, and protocols combining exercise with nutritional supplementation. Research is also beginning to explore the role of prehabilitation for patients prior to dialysis and kidney transplantation.

Studies continue to demonstrate wide-ranging benefits of exercise across CKD; however, implementation of exercise remains scarce. Future research needs include evaluating the efficacy of larger and/or more comprehensive interventions on clinically important outcomes. It is hoped with increasing global evidence, high-quality clinical studies, and sustained clinician and patient engagement, exercise programs will become better prioritized in the nephrology field.