bluuebunny/crossref_metadata_2025 huggingface dataset:
The Irish Supreme Court
Authors: Brice Dickson
Published: March 2019

This book examines the jurisprudence of the Supreme Court of Ireland since its creation in 1924. It sets out the origins of the Court, explains how it operated during the life of the Irish Free State (1922-1937), and considers how it has developed various fields of law under Ireland’s 1937 Constitution, especially after the ‘re-creation’ of the Court in 1961. As well as constitutional law, the book looks at the Court’s views on the status and legal system of Northern Ireland, administrative law, criminal justice and personal and family law. There are also chapters on the Supreme Court’s interaction with European Union law and with the European Convention on Human Rights. The argument throughout is that, while the Court has been well served by many of its judges, who on occasion have manifested a healthy degree of judicial activism, there are still several legal fields in which the Court has not developed its jurisprudence as clearly or as imaginatively as it might have done. It has often displayed undue conservatism and deference. For many years its performance was hampered by its extreme workload, generated by its inability to control the number of appeals brought to it. However, the creation of a new Court of Appeal in 2014 has freed up the Supreme Court to act in a manner more analogous to that adopted by supreme courts in other common law countries. The Court’s future looks bright.
2 The Origins of the Supreme Court
Authors: Brice Dickson
Published: March 2019

This chapter provides relevant historical context by explaining how Southern Ireland broke away from the United Kingdom in 1922 and became a Dominion under the name of the Irish Free State. It describes how the court system developed before and after the partition of Ireland, focusing on the transition from the Dáil Éireann courts to the proposals in the report of the Judiciary Committee in 1923, which led to the Courts of Justice Act 1924. The nature of the proposed Supreme Court of Ireland is compared with that of Supreme Courts in other dominions at that time, with particular regard to the judicial power to subject legislation to constitutional review. Despite references to Canada in the Irish Free State’s Constitution, few lessons were drawn from the experience of Canada’s Supreme Court or any other top national court.
8 Administrative Law
Authors: Brice Dickson
Published: March 2019

This chapter explains the history of ‘State Side orders’ and the development of applications for judicial review of administrative (as opposed to legislative) action in Ireland. It sets out the ramifications of the ultra vires doctrine, highlighting the East Donegal case. The importance of principles of natural justice is stressed, considering cases such as Healy. Then the way the term ‘reasonableness’ has been unpacked in Ireland is subjected to close examination, with reference to cases such as Keegan and O’Keeffe. The Meadows case and the doctrine of proportionality are analysed, as is the extent to which the Supreme Court adheres to a deferential approach to administrative bodies. Throughout this chapter the subtle differences between the Irish and English approaches to administrative law are singled out for attention and critique
11 The Supreme Court and the European Union
Authors: Brice Dickson
Published: March 2019

This chapter charts the way in which the Irish Supreme Court has applied the law of the European Community/Union. It takes the reader through several seminal cases which illustrate the Court’s readiness to accommodate EC/EU standards within domestic Irish law. These include the Campus Oil case, the Crotty case, the Meagher case, the Maher case, and the Pringle case. This entails explaining and critiquing the Supreme Court’s approach to the doctrine of separation of powers and the status of EC/EU law within the Irish Constitution. The case-law in this field illustrates how activist the Supreme Court can sometimes be. The chapter ends by looking at other respects in which the Supreme Court has interacted with EU law
Platelet-derived microparticles from recurrent miscarriage associated with antiphospholipid antibody syndrome influence behaviours of trophoblast and endothelial cells
Authors: Zhou Qian , Lian Yan , Zhang Yan , Li Lei , Li Hongyan , Shen Di , Zhou Yu , Zhang Meihua , Lu Yuan , Liu Jing , Xia Yu , Wang Xietong
Published: March 2019

Platelet-derived microparticles (PMPs) are a type of microparticle budding from platelets undergoing activation or apoptosis in many autoimmune diseases, including antiphospholipid antibody syndrome (APS). PMPs may also contribute to recurrent miscarriage, although the exact mechanism is unclear. The aim of this study was to determine the potential biological mechanism by which abnormal PMP activation may affect recurrent miscarriage. PMPs were counted by fluorescence-activated cell sorting (FACS) and compared between the healthy control (HC) and recurrent miscarriage/APS groups. Different effects of PMPs isolated by FACS from patients with recurrent miscarriage/APS and HCs were explored. Capillary electrophoresis immunoquantification, RT-qPCR, Luminex xMAP and immunofluorescence staining were performed to investigate all these different effects of PMPs. We found that the difference in the counts of PMP was not significant. However the expression of the inflammatory cytokine tumour necrosis factor-α (TNF-α) and the adhesion molecules intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were increased by PMPs derived from the recurrent miscarriage/APS group. PMPs isolated from patients with recurrent miscarriage/APS also more potently stimulated monocyte recruitment, inhibited angiogenesis and promoted human umbilical vein endothelial cell (HUVEC) apoptosis, in comparison to PMPs from HCs matched for gestational week. Moreover, PMPs could be ternalized by HTR-8/SVneo cells and could increase apoptosis of these cells and decrease trophoblastic invasion and migration. To supplement our work, the limited sample size needs to be increased, and further in-vivo work is necessary. Findings from this study indicate that abnormal activation of PMPs contributes to recurrent miscarriage/APS progression and provides potential therapeutic targets.
A tunable assay for modulators of genome-destabilizing DNA structures
Authors: del Mundo Imee M A , Cho Eun Jeong , Dalby Kevin N , Vasquez Karen M
Published: March 2019

Regions of genomic instability are not random and often co-localize with DNA sequences that can adopt alternative DNA structures (i.e. non-B DNA, such as H-DNA). Non-B DNA-forming sequences are highly enriched at translocation breakpoints in human cancer genomes, representing an endogenous source of genetic instability. However, a further understanding of the mechanisms involved in non-B DNA-induced genetic instability is needed. Small molecules that can modulate the formation/stability of non-B DNA structures, and therefore the subsequent mutagenic outcome, represent valuable tools to study DNA structure-induced genetic instability. To this end, we have developed a tunable Förster resonance energy transfer (FRET)-based assay to detect triplex/H-DNA-destabilizing and -stabilizing ligands. The assay was designed by incorporating a fluorophore-quencher pair in a naturally-occurring H-DNA-forming sequence from a chromosomal breakpoint hotspot in the human c-MYC oncogene. By tuning triplex stability via buffer composition, the assay functions as a dual-reporter that can identify stabilizers and destabilizers, simultaneously. The assay principle was demonstrated using known triplex stabilizers, BePI and coralyne, and a complementary oligonucleotide to mimic a destabilizer, MCRa2. The potential of the assay was validated in a 384-well plate with 320 custom-assembled compounds. The discovery of novel triplex stabilizers/destabilizers may allow the regulation of genetic instability in human genomes.
Prediction of the effect of dapagliflozin on kidney and heart failure outcomes based on short-term changes in multiple risk markers
Authors: Idzerda Nienke M A , Stefansson Bergur V , Pena Michelle J , Sjostrom David C , Wheeler David C , Heerspink Hiddo J L
Published: March 2019

Background

Besides improving glucose control, sodium-glucose co-transporter 2 inhibition with dapagliflozin reduces blood pressure, body weight and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes (T2DM). The parameter response efficacy (PRE) score was developed to predict how short-term drug effects on cardiovascular risk markers translate into long-term changes in clinical outcomes. We applied the PRE score to clinical trials of dapagliflozin to model the effect of the drug on kidney and heart failure (HF) outcomes in patients with T2DM and impaired kidney function.

Methods

The relationships between multiple risk markers and long-term outcome were determined in a background population of patients with T2DM with a multivariable Cox model. These relationships were then applied to short-term changes in risk markers observed in a pooled database of dapagliflozin trials (n = 7) that recruited patients with albuminuria to predict the drug-induced changes to kidney and HF outcomes.

Results

A total of 132 and 350 patients had UACR >200 mg/g and >30 mg/g at baseline, respectively, and were selected for analysis. The PRE score predicted a risk change for kidney events of −40.8% [95% confidence interval (CI) −51.7 to −29.4) and −40.4% (95% CI −48.4 to −31.1) with dapagliflozin 10 mg compared with placebo for the UACR >200 mg/g and >30 mg/g subgroups. The predicted change in risk for HF events was −27.3% (95% CI −47.7 to −5.1) and −21.2% (95% CI −35.0 to −7.8), respectively. Simulation analyses showed that even with a smaller albuminuria-lowering effect of dapagliflozin (10% instead of the observed 35% in both groups), the estimated kidney risk reduction was still 26.5 and 26.8%, respectively.

Conclusions

The PRE score predicted clinically meaningful reductions in kidney and HF events associated with dapagliflozin therapy in patients with diabetic kidney disease. These results support a large long-term outcome trial in this population to confirm the benefits of the drug on these endpoints.
Association Between Spinal Cord Stimulation and Top-Down Nociceptive Inhibition in People With Failed Back Surgery Syndrome: A Cohort Study
Authors: Goudman Lisa , Brouns Raf , De Groote Sander , De Jaeger Mats , Huysmans Eva , Forget Patrice , Moens Maarten
Published: March 2019

Background

Descending nociceptive inhibitory pathways often malfunction in people with chronic pain. Conditioned pain modulation (CPM) is an experimental evaluation tool for assessing the functioning of these pathways. Spinal cord stimulation (SCS), a well-known treatment option for people with failed back surgery syndrome (FBSS), probably exerts its pain-relieving effect through a complex interplay of segmental and higher-order structures.

Objective

To the best of our knowledge, no clinical studies have thoroughly investigated the associations between SCS and CPM.

Design

This was a prospective cohort study in people with FBSS.

Methods

Seventeen people who had FBSS and were scheduled for SCS were enrolled in this study. The CPM model was evaluated at both sural nerves and was induced by electrical stimulation as the test stimulus and the cold pressor test as the conditioning stimulus.

Results

Before SCS, less than 30% of the participants with FBSS showed a CPM effect. Significant increases in the electrical detection threshold on the symptomatic side and the nonsymptomatic side were found. On the symptomatic side, no differences in the numbers of CPM responders before and after SCS could be found. On the nonsymptomatic side, more participants showed a CPM effect during SCS. Additionally, there were significant differences for CPM activation and SCS treatment.

Limitations

Limitations were the small sample size and the subjective outcome parameters in the CPM model.

Conclusions

This study revealed a bilateral effect of SCS that suggests the involvement of higher-order structures, such as the periaqueductal gray matter and rostroventromedial medulla (key regions in the descending pathways), as previously suggested by animal research.
You Will or UWOn’t: Trustees’ Compliance with Unexplained Wealth Orders
Authors: Stringer-Fehlow Mariel , Steen Peter
Published: March 2019

Much has been written about Unexplained Wealth Orders (UWOs) since they came into existence on 31 January 2018; however, very little attention has been paid—at least in the legal press—to the potential impact such Orders could have on Trustees (both offshore and onshore). Following recent decisions by Supperstone J in late 2018 (National Crime Agency v Mrs A [2018] EWHC 534 (Admin)), we now know a little more about how the Court will approach UWOs, in particular where there is an offshore/trust element. This article focuses on highlighting the most pertinent issues which will likely need to be addressed by trustees and beneficiaries: should either party be served with a UWO, or be connected to someone who is served? The UWO legislation remains in its infancy, however, it is clear that enforcement agencies increasingly regard UWOs as useful tools in their armoury. The interface between UWOs and trusts is likely to create heightened tension between beneficiaries under intense pressure from the English Court, and offshore trustees looking to protect themselves and their beneficiaries. This article is aimed at increasing the awareness of trustees and advisers of the potential impact of UWOs, and in particular the fact that UWOs will not just affect those in the United Kingdom. The respondent to a UWO does not need to live in the United Kingdom, and the property which can be the subject of a UWO also does not need to be located in the United Kingdom, so offshore individuals need to also be aware of UWOs and their potential ramifications.
Phytophthora infestans Sporangia Produced in Artificial Media and Plant Lesions Have Subtly Divergent Transcription Profiles but Equivalent Infection Potential and Aggressiveness
Authors: Leesutthiphonchai Wiphawee , Judelson Howard S.
Published: March 2019

Sporangia of the potato late blight agent Phytophthora infestans are often used in studies of pathogen biology and plant responses to infection. Investigations of spore biology can be challenging in oomycetes because their sporangia are physiologically active and change in response to environmental factors and aging. Whether sporangia from artificial media and plant lesions are functionally equivalent has been a topic of debate. To address these issues, we compared the transcriptomes and infection ability of sporangia from rye-sucrose media, potato and tomato leaflets, and potato tubers. Small differences were observed between the mRNA profiles of sporangia from all sources, including variation in genes encoding metabolic enzymes, cell-wall-degrading enzymes, and ABC transporters. Small differences in sporangia age also resulted in variation in the transcriptome. Taking care to use sporangia of similar maturity, we observed that those sourced from media or plant lesions had similar rates of zoospore release and cyst germination. There were also no differences in infection rates or aggressiveness on leaflets, based on single-spore inoculation assays. Such results are discordant with those of a recent publication in this journal. Nevertheless, we conclude that sporangia from plant and media cultures are functionally similar and emphasize the importance of using “best practices” in experiments with sporangia to obtain reliable results.
Making better wound management decisions
Authors: Keim Amy , Marinucci James
Published: March 2019

Clinicians make wound management decisions based on scientific research of varying quality as well as personal and observed habits, anecdotal evidence, and even misinterpreted data. This article examines some common traumatic wound management topics and discusses appropriate decision-making for wound management.
Successful Management of Gamma-hydroxybutyrate (GHB) Withdrawal Using Baclofen as a Standalone Therapy: A Case Report
Authors: Habibian Sonia , Ahamad Keith , McLean Mark , Socias Maria Eugenia
Published: March 2019

Background:

Gamma-hydroxybutyrate (GHB)—a GABA-B agonist—can lead to a use disorder, and a withdrawal syndrome similar to that of alcohol. At present, evidence is lacking for how to best manage GHB withdrawal, and often clinicians rely on alcohol withdrawal management approaches, using medications like benzodiazepines (BZD). However, BZD doses needed to control GHB withdrawal symptoms are typically much higher than those required for alcohol, posing significant safety risks. Novel approaches include the use of baclofen as an adjunct to BZD, allowing reductions in BZD requirements. While the use of baclofen as monotherapy may result in even greater risk reductions, research to support this approach is limited.

Case:

We present a case of a 26-year-old female with severe GHB use disorder and history of severe withdrawal symptoms, whose withdrawal was successfully, managed using baclofen alone.

Conclusion:

In keeping with other case reports, baclofen appears to have potential to be used in the management of GHB withdrawal. Here, we presented a case of severe GHB withdrawal which was managed solely by baclofen. Clinical research is needed to evaluate baclofen's potential as a standalone treatment for GHB withdrawal.
Applying Critical Race Feminism and Intersectionality to Narrative Inquiry
Authors: Clark Nancy , Saleh Nasrin
Published: March 2019

Racism in nursing can be positioned through institutional forms of gendered, racialized, and religious structures. Muslim nurses who choose to honor the Islamic practice of donning hijab may be at risk of experiencing racism in contexts of post–September 11 era and the war on terror. Critical race feminism and intersectionality are theoretical frameworks that when applied to narrative inquiry can illuminate the standpoint of Muslim nurses donning hijab by providing a counternarrative as a point of resistant to racism in nursing.
Update on transarterial approaches to locoregional treatment in hepatocellular carcinoma
Authors: Delhaye Corentin , Hendlisz Alain , Vouche Michael
Published: March 2019

Purpose of review

This review explores current knowledge and recent data about vascular-centered locoregional treatments and proposes alternate algorithms.

Recent findings

Hepatocellular carcinoma represents the sixth most common neoplasm worldwide. Currently, the Barcelona Clinic Liver Cancer (BCLC) staging is the most commonly used in Europe for treatment allocation. According to this classification, European Society for Medical Oncology (ESMO) guidelines currently recommend transarterial chemoembolization for intermediate stage HCC and systemic treatments, such as, sorafenib in more advanced stages. However, strong evidences are still lacking to conclude to the superiority of one technique over another, as the optimal treatment choice remains challenging and should take into consideration more clinical, biological and imaging findings than reported in the BCLC staging system, such as patient age or clinical status, tumor characteristics (including distribution and heterogeneity), tumor vascularization and concomitant portal hypertension or biliary anomalies.

Many controversies remain, in particular, the relative place of bland embolization versus chemoembolization, the clinical benefit of drug-eluting bead chemoembolization (DEB-TACE) over conventional chemoembolization (cTACE), as well as the real place of radioembolization in general setting as well as innovative applications, such as radiation segmentectomy and radiation lobectomy.
Laparoscopic-assisted Versus Open D2 Gastrectomy for Advanced Gastric Cancer in Highly Selective Patients
Authors: Huang Xin , Du Hao , Aihemaiti Maimaiti , Liu Teng , Chen Ningyuan , Yu Wenbin , Hu Sanyuan , Liu Shaozhuang
Published: March 2019

Objectives:

The feasibility and efficacy of laparoscopic-assisted D2 gastrectomy (LAD2G) for advanced gastric cancer (AGC) remain controversial. We conducted a prospective cohort study to provide a comprehensive comparison of LAD2G and open D2 gastrectomy (OD2G) for AGC.

Materials and Methods:

Between April 2016 and December 2017, patients with clinical stage T2-4aN0-3M0 gastric cancer were enrolled and assigned to either LAD2G or OD2G group. The primary endpoint was short-term surgical and chemotherapy outcomes. The postoperative pain and perioperative anxiety were compared as the secondary endpoint to indicate perioperative life quality.

Results:

A total of 110 patients in LAD2G group and 238 patients in OD2G group were included. The 2 groups showed similar number of retrieved lymph nodes (29.85±6.52 vs. 30.60±5.37, P=0.069) and postoperative morbidity (21.01% vs. 21.82%, P=0.888). A total of 84.4% of patients in LAD2G group and 75.6% in OD2G group received adjuvant chemotherapy (AC) (P=0.069). The mean time interval to AC was shorter in LAD2G group (34±13.74 vs. 40.78±18.78 d, P<0.001). Furthermore, LAD2G was superior to OD2G in terms of earlier postoperative recovery, faster relief of postoperative pain, and lower postoperative anxiety.

Conclusions:

LAD2G is feasible for AGC in experienced centers. Patients after LAD2G tended to have earlier initiate of AC. LAD2G could provide more rapid postoperative recovery and relief of postoperative pain, along with lower postoperative anxiety.
Outcomes of Adjuvant Radiotherapy Following Negative Surgical Margins for Cutaneous Squamous Cell Carcinoma
Authors: Miller Jonathan , Chang Timothy , Schwartz David , Peters Margot , Baum Christian
Published: March 2019

BACKGROUND

The role of adjuvant radiotherapy (ART) for cutaneous squamous cell carcinoma (cSCC) following negative surgical margins is unclear.

OBJECTIVE

To retrospectively examine the clinical outcomes in a cohort of patients with cSCC who completed ART after Mohs micrographic surgery or wide local excision with negative margins.

METHODS AND MATERIALS

After the institutional review board approval, a retrospective review was conducted of all patients with cSCC treated in the Mayo Clinic Department of Radiation Oncology from March 10, 1998, through April 26, 2013. Inclusion criteria were age >18 years, resection with negative histologic surgical margins, and completion of ART.

RESULTS

Thirty-two patients met the inclusion criteria: 15 patients died, 12 without evidence of disease related to cSCC. Three patients developed recurrent disease, all with poorly differentiated cSCC, > 2 cm in clinical diameter, perineural invasion, and Brigham and Women's (BWH) stage T2b/T3; 2 of 3 patients were immunosuppressed; and 2 of 3 patients died of cSCC-related causes.

CONCLUSION

These data suggest that the combination of surgical resection and ART is a reasonable option for Brigham and Women's T2b/T3 tumors.
Squamous Cell Carcinoma In Situ With Occult Invasion: A Tertiary Care Institutional Experience
Authors: Newsom Emily , Connolly Karen , Phillips William , Lee Erica , Rossi Anthony , Navarrete-Dechent Cristian , Busam Klaus , Dusza Stephen W. , Nehal Kishwer
Published: March 2019

BACKGROUND

The rate of occult invasive disease within biopsy-proven squamous cell carcinoma in situ (SCCIS) is not well defined.

OBJECTIVE

To examine the rate of occult invasion in SCCIS.

METHODS

An institutional-wide pathology database was retrospectively searched for “squamous cell carcinoma in situ” over a 6-year period, and the treatment modality and final pathology results were analyzed for evidence of invasion. In addition, consecutive tumor blocks from Mohs micrographic surgery (MMS) cases of SCCIS were prospectively analyzed for invasion.

RESULTS

The rate of occult invasion for biopsy-proven SCCIS treated with excision was 4.0% (N = 49) and for the MMS margins was 3.5% (N = 310). For the prospective MMS tumor block analysis, the rate of occult invasion was 10.1% (N = 69). No clinical factors (age, sex, location, or size) correlated with increased risk of invasion. All invasive SCCs detected were superficial and well differentiated.

CONCLUSION

The rate of occult invasion for biopsy-proven SCCIS ranged from 3.5% to 10.1%. The detected rate of invasion varies based on the method of excision and pathology processing of specimens. The rate of invasion should be considered when managing SSCIS.
Efficacy and Safety of PrabotulinumtoxinA for the Treatment of Glabellar Lines in Adult Subjects: Results From 2 Identical Phase III Studies
Authors: Beer Kenneth R. , Shamban Ava Theresa , Avelar Rui L. , Gross John E. , Jonker Anneke ,   and the EV-001/EV-002 Study Group
Published: March 2019

BACKGROUND

PrabotulinumtoxinA is a 900-kDa botulinum toxin Type A produced by Clostridium botulinum.

OBJECTIVE

To investigate the efficacy and safety of prabotulinumtoxinA for the treatment of glabellar lines.

MATERIALS AND METHODS

Adult subjects (n = 330 in EV-001; n = 324 in EV-002) with moderate to severe glabellar lines at maximum frown on the 4-point Glabellar Line Scale (GLS; 0 = no lines, 1 = mild, 2 = moderate, and 3 = severe) were enrolled in 1 of 2 identical 150-day, double-blind, placebo-controlled, single-dose, Phase III studies. Subjects were randomized 3:1 to receive 20-U prabotulinumtoxinA or placebo. The primary efficacy end point was the proportion of responders on Day 30 where the investigator and subject independently agreed that a ≥2-point improvement had occurred on the GLS at maximum frown from Day 0. Adverse events (AEs) were evaluated throughout the study.

RESULTS

Responder rates in the prabotulinumtoxinA and placebo groups were 67.5% and 1.2% in EV-001 and 70.4% and 1.3% in EV-002; absolute differences between groups were 66.3% and 69.1% in EV-001 and EV-002, respectively (both p < .001). No serious AE in either study was assessed as study drug related.

CONCLUSION

In these studies, a single dose of 20-U prabotulinumtoxinA was safe and effective for the treatment of glabellar lines.
An Observational Study of the Safety and Efficacy of Tissue Stabilized–Guided Subcision
Authors: Geronemus Roy G. , Kilmer Suzanne L. , Wall Simeon H. , Green Jeremy B. , Cohen Joel L. , Weiss Robert A. , Alster Tina S. , Kaminer Michael S. , Gupta Anjali
Published: March 2019

BACKGROUND

Cellulite is a common female cosmetic concern for which there are few treatment options with long-term effectiveness data. The aim of this multisite prospective registry study was to collect observational data on the real-life clinical use of a tissue stabilized–guided subcision (TS-GS) system for long-term improvement of cellulite appearance.

METHODS

Fifty-three subjects were enrolled and received a single treatment using the TS-GS system. Physicians treated the subjects according to their standard of care. Global Aesthetic Improvement Scale (GAIS) was completed by the patient and clinician assessing overall aesthetic improvement after 180 days. Treatment parameters, pain scores, quality of life data, and expected treatment effects and adverse events were also recorded throughout the study.

RESULTS

The patient and physician GAIS scores at Day 180 revealed an overall improvement in 91% and 96% of patients, respectively. Quality of life and self-confidence scores also improved through 180 days. No serious adverse events were reported. Expected treatment effects were similar to those reported in the pivotal trial supporting FDA clearance.

CONCLUSION

This study demonstrated significant improvement in the appearance of cellulite after a single treatment session in patients with moderate-to-severe cellulite. These results are consistent with the previously published the pivotal study data.
Efficacy and Safety of Prabotulinumtoxin A and Onabotulinumtoxin A for Crow's Feet: A Phase 3, Multicenter, Randomized, Double-Blind, Split-Face Study
Authors: Cheon Hye In , Jung Nari , Won Chong Hyun , Kim Beom Joon , Lee Yang Won
Published: March 2019

BACKGROUND

Prabotulinumtoxin A has been shown to have efficacy for the treatment of upper-limb spasticity and improvement of moderate to severe glabellar lines. However, the efficacy and safety of prabotulinumtoxin A for crow's feet have not been evaluated.

OBJECTIVE

This study compared the efficacy and safety of prabotulinumtoxin A and onabotulinumtoxin A in the treatment of crow's feet.

PATIENTS AND METHODS

A multicenter, randomized, double-blind, active-controlled, split-face study was conducted in subjects with bilateral symmetric, moderate to severe crow's feet at maximum smile. The investigators assessed the severity of crow's feet by using the facial wrinkle scale, and the subjects reported the improvement in severity, their subjective satisfaction, and perceived age. The primary efficacy outcome was the proportion of subjects with Grade 0 or 1 severity of crow's feet at maximum smile at Week 4 as assessed by the investigators.

RESULTS

In the primary efficacy outcome assessment, there was no significant difference between the 2 groups (prabotulinumtoxin A, 65.02%; onabotulinumtoxin A, 62.56%; p = .0956). All secondary efficacy outcomes were also achieved. Adverse events related to injection were mild and recovered spontaneously.

CONCLUSION

Prabotulinumtoxin A and onabotulinumtoxin A have comparable efficacy and safety in the treatment of crow's feet.
Clinical Assessment of 2 Licensed AbobotulinumtoxinA Injection Volumes for the Treatment of Glabellar Lines
Authors: Kaufman Joely , Cohen Joel L. , Peredo Marina I. , Jonas Brandie , Down Rebecca , Nogueira Alessandra
Published: March 2019

BACKGROUND

Two licensed reconstitution volumes may be used to achieve the recommended abobotulinumtoxinA (ABO) dose for glabellar line correction.

OBJECTIVE

Comparison of efficacy, safety, and subject satisfaction concerning treatment of moderate to severe glabellar lines with 2 different ABO reconstitution volumes.

MATERIALS AND METHODS

Phase IV, prospective, randomized, multicenter, subject- and evaluator-blinded study: 60 subjects received 1 ABO (50 units) treatment, administered as a 1.5- or 2.5-mL reconstitution. Primary objective was Day 30 improvements (≥1-point) in glabellar line severity. Onset of effect, duration, subject satisfaction, and treatment-related adverse events (AEs) were assessed.

RESULTS

At Day 30, 90.0% and 86.7% of subjects achieved ≥1-point improvements with 1.5- and 2.5-mL reconstitutions, respectively. Median time to onset of effect was 48 hours after treatment. At 24 hours, 26.7% achieved ≥1-point improvements with the 2.5-mL reconstitution versus 6.7% with the 1.5-mL reconstitution. Maximum response was at Day 14, and >40% maintained efficacy through Day 120 in each group. High subject satisfaction was sustained throughout observation. Most AEs were mild. No serious AEs were reported.

CONCLUSION

Both ABO reconstitutions were well tolerated and effective in correcting glabellar lines with no significant differences concerning efficacy or duration of effect. No serious AEs were reported.
Internal Mammary Artery and Vein Perforator Vessels as Troubleshooter Recipient Vessels
Authors: Fansa Hisham
Published: March 2019

In autologous breast reconstruction, the internal mammary artery (IMA) and internal mammary vein (IMV) are the standard recipient vessels. Recently, the perforator vessels of the IMA and IMV were found to be a safe alternative as recipient vessels cause less morbidity and allow adequate flap. We describe 2 cases in which the IMA and IMV perforators were used as additional recipient vessels to overcome intraoperatively occurred complications. The IMA and IMV perforators have some advantages over the IMA/IMV: (1) the dissection is done superficially and directly from the mastectomy site. Flap positioning is facilitated. (2) There is no need to remove a rib, which reduces postoperative pain and possible contour deformities. (3) Possible injuries to the pleura are avoided. (4) The IMA is spared for possible cardiac revascularization. Disadvantages can be that (1) the IMA perforators are not always present with the required caliber, (2) the position of the perforators is not suitable to adequately position the flap, and (3) dissection of the IMA perforators and their anastomoses has a learning curve. In the presented cases, the IMA and IMV perforators have proven to offer a simple solution to avoid complications. The additional dissection is done from the same recipient site, and there is no further dissection or incision necessary at the axilla or to explore the cephalic vein. This keeps morbidity and operation time low. Therefore, we suggest keeping the IMA and IMV perforators in mind not only as primary recipient vessels but also as a possible solution for intraoperatively occurred complications.
Maternal and Fetal Thyroid Physiology
Authors: STERRETT MARY
Published: March 2019

This study was a brief review of maternal and fetal thyroid function and pathology during pregnancy.
Effects of Kefir on Quality of Life and Sleep Disturbances in Postmenopausal Women
Authors: Özcan Handan , Oskay Ümran , Bodur Ali Fuat
Published: March 2019

The aim of this study is to identify the effects of kefir, an alternative treatment method, on quality of life and sleep disturbances in postmenopausal women. In this study, it is seen that kefir has positive effects on sleep disturbances, depression, and quality of life in postmenopausal women.
Monitoring and Dose Assessment for Children Following a Radiation Emergency—Part II: Calibration Factors for Thyroid Monitoring
Authors: Li Chunsheng , Tremblay Marilyn , Capello Kevin , Kurihara Osamu , Youngman Mike , Etherington George , Ansari Armin , López María Antonia , Franck Didier , Dewji Shaheen
Published: March 2019

Past radiological and nuclear accidents have demonstrated that monitoring a large number of children following a radiological and nuclear emergency can be challenging, in accommodating their needs as well as adapting monitoring protocols and applying age-specific biokinetics to account for various ages and body sizes. This paper presents the derived calibration factors for thyroid monitoring of children of all ages recommended by the International Commission on Radiological Protection using four selected detectors at given times following a short-term (acute) intake of 131I by inhalation. These calibration factors were derived by Monte Carlo simulations using the models of various detectors and pediatric voxel phantoms. A collection of lookup tables is presented in this paper which may be directly used as a quick reference by emergency response personnel or technical experts performing thyroid monitoring and assessment without doing time-consuming calculations.
Demonstrating Compliance With Proposed Reduced Lens of Eye Dose Limits in Nuclear Medicine Settings
Authors: Demeter Sandor , Goertzen Andrew L. , Patterson Judy
Published: March 2019

Based on ongoing research on ionizing radiation thresholds for cataracts, the International Commission on Radiological Protection has proposed new guidelines lowering the annual occupational lens of eye dose limit from 150 mSv to 20 mSv. The International Atomic Energy Agency has operationalized these new guidelines. Subsequently, national/regional radiation protection regulators are reviewing their lens of eye dose limits with an aim of moving towards the proposed new limits, resulting in licensees having to demonstrate compliance. In health care settings, fluoroscopic interventional practices generally have higher lens of eye doses and nuclear medicine settings generally have lower doses. A prospective cohort (n = 19) of nuclear medicine technologists wore dedicated lens of eye dosimeters for a 3 mo period synchronized with their body dosimeter schedules. The lens of eye dosimeters were validated to have a linear response in the anticipated dose ranges. The participants worked in a relatively high-volume nuclear medicine practice, which included general and cardiac, positron emission tomography/computed tomography, radiopharmacy, and cyclotron operations. The annualized dose ranges were 0.0–3.68 mSv (lens of eye) and 0.48–4.72 mSv (whole body). There was a good correlation between lens of eye and body dosimeter readings (R
2 = 0.67). There were no significant differences in lens of eye dose by work type, worker sex, or side on which the dosimeter was worn. The findings should be generalizable to other similar practices, especially in North America, and should be sufficient to demonstrate regulatory compliance in nuclear medicine settings with the proposed new lens of eye dose limits.
An Alternative Approach to Estimating Instrument Decision Thresholds for Clearance of Personal Property From Accelerator Facilities
Authors: Schaefer Charles Wesley
Published: March 2019

Personal property exposed to particle beams and stray radiation at high-energy particle accelerators may contain induced volumetric radioactivity. At both the Brookhaven National Laboratory’s (BNL) Collider-Accelerator and National Synchrotron Light Source II Facilities this radioactivity contains both gamma-emitting and beta-emitting radionuclides. The US Department of Energy (US DOE) recently published Technical Standard 6004-2016. This standard provides radionuclide-specific volumetric screening levels (Bq g−1) below which accelerator materials are eligible for clearance and release from radiological control. The standard also establishes several approaches for decision-making relative to the clearance process implemented, one of which is the “Indistinguishable from Background” (IFB) approach. BNL implements the IFB approach for survey of potentially activated accelerator materials. Radiological control technicians perform on-contact measurements using portable scintillators that are sensitive to gamma and x-ray radiation. Instrument decision thresholds are usually estimated by measuring total background counts over a pre-determined counting interval using an integrating count-rate instrument and then applying an appropriate confidence level factor. Measurement results obtained in a low background area are then directly compared to these detection thresholds. This paper presents an alternative statistical approach using logistic regression for estimating instrument decision thresholds for small-mass items using the IFB method and compares them to established release criteria. On-contact Micro-R meter measurements are correlated with analytical data obtained for activated materials weighing 0.3 kg to 3 kg. Analytical sample results show that 60Co and 22Na accounted for more than 90% of total sample radioactivity. 60Co and 22Na emit high-energy gamma rays and are both group one radionuclides as defined in DOE-6004-2016. For this size material the results show that the probability of detecting residual volumetric radioactivity at the Group One screening level concentration of 0.11 Bq g−1 under normal field conditions is about 68%. This increases to 95% at 0.16 Bq g−1. The 95% confidence interval is 0.09 Bq g−1 to 0.23 Bq g−1. Grouping low-mass items during the survey process could mitigate this concern if all items are expected to have similar activity concentrations.
Rebound Thrombocytosis after Induction Chemotherapy is a Strong Biomarker for Favorable Outcome in AML Patients
Authors: Schnell Bianca R. , Seipel Katja , Bacher Ulrike , Jeker Barbara , Mueller Beatrice U. , Banz Yara , Novak Urban , Pabst Thomas
Published: March 2019

Supplemental Digital Content is available in the text
THE EFFECT OF AGE ON AFLIBERCEPT (EYLEA) RESPONSE IN DIABETIC MACULAR EDEMA
Authors: Ozsaygili Cemal , Duru Zeynep , Cicek Ayse , Ulusoy Dondu Melek , Demirtas Atilim Armagan , Duru Necati
Published: March 2019

Purpose:

To investigate the effect of age on aflibercept (Eylea) response in macular edema secondary to treatment-naive diabetic eyes.

Methods:

Two hundred seventy-three eyes of 273 treatment-naive patients with macular edema secondary to diabetes mellitus were enrolled in this study. The patients in the study were divided into the following 4 groups according to their ages: Group 1 (40–50 years), Group 2 (51–60 years), Group 3 (61–70 years), and Group 4 (>70 years). Three consecutive injections at intervals of 1 month were applied to all diabetic patients. The efficacy of the aflibercept treatment on macular edema according to age groups was assessed by optical coherence tomography by comparing the central foveal thickness (CFT) values and mean visual acuity changes after initial and three loading dose injections.

Results:

After three consecutive aflibercept injections, the mean reduction of CFT in Groups 1, 2, 3, and 4 were −256.4 ± 110.9, −197.4 ± 96.4, −189.4 ± 110.8, and −186.2 ± 118.9 µm, respectively. The changes of CFT was significantly different between age groups (P = 0.003, analysis of covariance). The improvement of visual acuity was significantly different in each group (P < 0.001 in all groups, paired-samples t-test), and changes of visual acuity was significantly different between age groups (P < 0.05, analysis of covariance). In addition, ages of patients were correlated with the mean reduction of CFT and mean improvement of visual acuity for the whole study group (r = −0.183, P = 0.002 for CFT; r = −0.682, P < 0.001 for visual acuity, Pearson correlation).

Conclusion:

In this study, it was observed that the efficacy of aflibercept treatment was found to be more effective in younger patients in treatment-naive diabetic macular edema patients.
MACULAR TELANGIECTASIA TYPE 2
Authors: Ersoz M. Giray , Hocaoglu Mumin , Sayman muslubas Isil , Arf Serra , Karacorlu Murat
Published: March 2019

Purpose:

The purpose of this study was to investigate the foveal avascular zone area and its perimeter, the acircularity index of the foveal avascular zone, the vessel density surrounding the foveal avascular zone, and the vessel density in the foveal, parafoveal, and perifoveal areas and their associations with best-corrected visual acuity, central foveal average thickness, and volume of ellipsoid zone–retinal pigment epithelium in patients with macular telangiectasia Type 2 (MacTel 2).

Methods:

We retrospectively reviewed medical records of 22 eyes of 22 patients with MacTel 2 and 24 eyes of 24 healthy controls. Eyes with MacTel 2 were graded according to optical coherence tomography angiography: 1) vascular anomalies temporal to the fovea; 2) vascular anomalies temporal and nasal to the fovea; 3) markedly diffuse circumferential vascular anomalies; and 4) neovascularization in the outer retina.

Results:

Acircularity index was higher and superficial–parafoveal vessel density was lower, in MacTel 2 group (all P < 0.05). Acircularity index was associated with the severity of the disease and had strong correlations with best-corrected visual acuity, ellipsoid zone–retinal pigment epithelium thickness, and ellipsoid zone–retinal pigment epithelium volume (all P < 0.05).

Conclusion:

In conclusion, the increase in acircularity index is correlated with the severity of the disease, the decrease in ellipsoid zone–retinal pigment epithelium thickness and volume, and the decrease in best-corrected visual acuity. It may be used to monitor patients with MacTel 2.
ENDOGENOUS ENDOPHTHALMITIS IN WESTERN AUSTRALIA
Authors: Gounder Pavindran Arumugam , Hille David Matthew , Khoo Ying Jo , Phagura Ravinder Singh , Chen Fred Kuanfu
Published: March 2019

Purpose:

To review the clinical features, microbiology spectrum, management, and outcomes of patients with endogenous endophthalmitis in Western Australia over a 16-year period.

Methods:

This is a retrospective chart review of all patients with endogenous endophthalmitis who presented to all tertiary ophthalmology departments between 2000 and 2015 in Western Australia.

Results:

Sixty-six eyes of 57 patients with endogenous endophthalmitis were identified, and follow-up data were available for a mean of 554 days. The average frequency was 1.6 per 1,000,000 population per year. Diabetes mellitus (33%) and intravenous drug use (30%) were the most common risk factors. Concurrent systemic infections included urinary tract infection (28%), pneumonia (23%), and endocarditis (21%). Among culture-positive cases (93%), 57% were bacterial and 43% were fungal. Visual acuity improved in 33 (50%) and declined in 15 eyes (22.7%). Baseline visual acuity and the presence of Gram-negative or filamentous fungi were the only predictors of final visual acuity (P = 0.023 and P = 0.001).

Conclusion:

The population frequency of endogenous endophthalmitis has not changed over 16 years despite the changing profile of pathogen and risk factors. Similar to previous studies in Asian and Western countries, visual and anatomical prognosis depends on initial visual acuity and isolated pathogen. Gram-negative and filamentous fungi culture predicted a worse visual outcome.
Changes in Corneal Wound Healing and Graft Biomechanics After Primary Penetrating Keratoplasty Versus Repeat Penetrating Keratoplasty
Authors: Abdelkader Almamoun
Published: March 2019

Purpose:

To evaluate and compare the influence of the wound healing process at the graft edge on corneal biomechanics after primary penetrating keratoplasty (PK) and repeat PK.

Methods:

This retrospective comparative study included 95 eyes: 35 eyes of 35 patients had PK, 40 eyes of 40 patients underwent repeat PK, and 20 eyes of 20 normal subjects served as the control group. The ocular response analyzer was used to measure and compare corneal hysteresis and corneal resistance factor among the study groups at least 6 months after all sutures were removed. In vivo confocal microscopy was used to study the corneal wound healing process at the graft edge in PK and repeat PK groups and to correlate these findings with corneal biomechanics.

Results:

Corneal hysteresis and corneal resistance factor were significantly lower in the PK group (6.71 ± 1.3 and 5.99 ± 1.2 mm Hg, respectively) as compared with the repeat PK group (9.4 ± 1.03 and 8.77 ± 1.1 mm Hg, respectively) (P < 0.0001). The repeat PK group demonstrated biomechanical parameters comparable with normal subjects (9.88 ± 1.29 and 9.24 ± 1.13 mm Hg, respectively) (P = 0.12). Confocal microscopy revealed more reflective and activated keratocytes at the graft edge in the repeat PK group as compared with the primary PK group.

Conclusions:

The healing process at the graft edge is the key to optimal corneal integrity after PK. Repeat PK stimulated more activated keratocytes than primary PK and hence a stronger healing response, providing superior corneal biomechanics comparable with normal subjects.