Heritable Genome Editing in a Global Context: National and International Policy Challenges

A central problem for the international governance of heritable germline gene editing is that there are important differences in attitudes and values as well as ethical and health care considerations around the world. These differences are reflected in a complicated and diverse regulatory landscape. Several publications have discussed whether reproductive uses would be legally permissible in individual countries and whether clinical applications could emerge in the context of regulatory gaps and gray areas. Systematic comparative studies that explore issues related to the governance of this technology from different national and international perspectives are needed to address the lack of knowledge in this area. In this research report, we contribute to filling this gap by presenting views of stakeholders in the United Kingdom on challenges to the governance of heritable genome editing. We present findings from a multistakeholder study conducted in the United Kingdom between October 2016 and January 2018 and funded by the Wellcome Trust. This research included interviews, literature analysis, and a workshop. We involved leading U.K. scientists, in vitro fertilization clinicians, and representatives from regulatory bodies, patient organizations, and other civil societal organizations, as well as fertility companies. Part one of this article explores stakeholder perceptions of possible global developments in heritable genome editing and associated risks and governance challenges. Part two presents a range of policy options that were generated during the workshop in relation to the challenges discussed in part one.     

Duration of dysmenorrhoea and extent of adenomyosis visualised by magnetic resonance imaging

OBJECTIVE: Enlargement of the junctional zone (JZ) on T2-weighted resonance imaging of the uterus has recently been established as the major criterion for adenomyosis in patients with endometriosis. This study was conducted to analyse the extent of adenomyosis using magnetic resonance imaging (MRI) and relate it to the duration of dysmenorrhoea. STUDY DESIGN: This was a prospective study of 70 patients presenting with the complaint of severe dysmenorrhoea. Forty patients (57%) reported dysmenorrhoea as their major complaint and 30 patients (43%) suffered additionally from infertility. Group I (n=40) consisted of patients with dysmenorrhoea of between 1 and 10 years' duration, group II (n=30) consisted of patients with dysmenorrhoea of longer than 11 years' duration. All patients underwent laparoscopy to detect the presence and degree of endometriosis, and all patients underwent T2-weighted resonance imaging of the uterus to detect the extent of adenomyosis by measurement of the "junctional zone". RESULTS: In group I, adenomyosis could be detected via MRI in 21 patients (52.5%), while 19 patients (47.5%) showed no signs of adenomyosis. By contrast, in group II a distinct enlargement of the JZ, as the major radiological criterion of adenomyosis, could be observed in 26 patients (87%), while only 4 patients (13%) revealed no signs of adenomyosis (p=0.04). The mean thickness of the JZ was significantly enlarged in group II (11.07 mm) compared with group I (6.38 mm; p<0.0001). The prevalence of adenomyosis in endometriosis after dysmenorrhoea of more than 11 years' duration was 87%. CONCLUSIONS: In deep infiltrating endometriosis, a correlation between a specific localisation and dysmenorrhoea can often not be found. Recently, endometriosis and adenomyosis have been believed to result from a common uterine disease, the dislocation of the basal endometrium. Our data clearly show that dysmenorrhoea of long duration in patients who have had endometriosis for over a threshold value of 11 years is significantly related to adenomyosis of the uterus. Hence, evaluation of adenomyosis using MRI should become a standard procedure in cases of dysmenorrhoea and endometriosis. Severe dysmenorrhoea of long duration should always focus clinical interest on adenomyosis of the uterus.     

Peroneus longus ligamentoplasty for chronic instability of the distal tibiofibular syndesmosis

The distal tibiofibular syndesmosmotic ligament complex is important for dynamic stability and congruency of the ankle joint. Syndesmotic lesions in the ankle fracture-dislocations are well recognized and classified systematically. Chronic insufficiency of the syndesmosis leads to a lateral shift of the talus and under eversion stress permits a pathological rotation of the talus. There is also retroversion of the distal fibula representing a painful deformity. Little experience exists with surgical reconstruction of the syndesmosis. This article describes a new ligamentoplasty with a split peroneus longus tendon graft that mimics the normal anatomic conditions of the syndesmotic complex in 16 patients with symptomatic chronic syndesmotic insufficiency after pronation-external rotation and pronation abduction injuries to the ankle joint. Postoperatively, no infections or hematomas were seen. One patient had asymptomatic breakage of the syndesmosis screw; one patient had a 10 degree decrease of dorsiflexion at the ankle because of a partial anterior tibiofibular synostosis. Fifteen of 16 patients had pain relief at a mean follow-up period of 16.4 months (range, 13-29 months); all patients had relief of the chronic swelling of the ankle and the giving way. The mean Karlsson score at follow-up was 88 (range, 70-100) points. It may be concluded that peroneus longus ligamentoplasty in a preliminary series resulted in reliable ankle stability and considerable pain relief in patients with chronic syndesmotic instability.     

Intraductal papillomas of the breast: diagnosis and management of 151 patients

Introduction

The assessment of papillary lesions continues to be a challenging area in breast radiology and pathology. The management of intraductal papillomas without atypia of the breast remains controversial. The purpose of the present study was to determine diagnostic accuracy of radiographical diagnosis, core biopsy, and surgical excision in papillary breast lesions.

Material and methods

By using files from 1995 to 2010, 151 cases of intraductal papilloma with or without atypia were identified. Patients were stratified as follows: core biopsy followed by surgical excision (n = 61), core biopsy alone (n = 19), and surgical excision alone (n = 71).

Results

The upstage rate of intraductal papillomas without atypia on core biopsy to atypia or malignancy on excision was 8.9%. Excision specimens revealed intraductal papillomas without atypia in 68 out of 71 cases, and atypical papillomas in 3 cases.

Conclusion

Our findings suggest that radiographic and histopathological diagnosis of intraductal papillomas show high accuracy and good concordance. In cases where the radiographic diagnosis reveals suspicious lesions core biopsy represents the first choice.     

Early identification of bacteria leading to central venous catheter contamination

Catheter-related bloodstream infections (CRBSI) are a common problem in patients after central venous catheterization. Using DNA analysis we compared bacteria found on the tip of central venous catheters removed because of clinical signs of CRBSI with bacteria found on needle, dilator, and guidewire used for insertion of these catheters. In five of seven central venous catheters removed because of clinical signs of CRBSI, bacteria on the catheter tip were genetically identical to bacteria found on the insertion device, proving that catheter contamination in these cases was caused by contacting bacteria during the initial puncture. These findings may be important for antibiotic prophylaxis or therapy in patients at risk for CRBSI. IMPLICATIONS: In five of seven central venous catheters removed because of clinical signs of catheter-related blood infections, DNA analysis showed bacteria found on the catheter tip to be identical with bacteria found on the puncture kits used for insertion of these catheters.     

High efficacy of integrated preventive measures against zoonotic cutaneous leishmaniasis in northern Afghanistan, as revealed by Quantified Infection Rates

Following an outbreak of more than 200 cases of zoonotic cutaneous leishmaniasis (ZCL) during 2004 and 2005 among International Security Assistance Force (ISAF) troops stationed in the Mazar-e Sharif (MeS) airport area, epidemiological investigations indicated the presence of a local high-density ZCL focus. Based on ZCL's specific transmission modes, density and seasonality, integrated preventive measures were continuously implemented from February 2006 at a German military camp constructed at MeS. Preventive techniques included such synergistic measures as skin repellents and insecticide-impregnated clothing, bednets and curtains, sand fly and rodent monitoring and control, extended habitat sanitation, and health education, all designed to achieve maximum protection against ZCL. Habitat alteration included: (a) erection of a 3.0 m high stone wall around the entire camp area; (b) removal of ≥30 cm of the upper earth layer throughout the site; (c) soil compaction and stone paving to a depth of ≥30 cm plus compaction of the surrounding area to a distance of 100 m outside the camp wall; and (d) regular eradication of vegetation. Aggressive implementation of these measures led to a 166-fold and 546-fold reduction in sand fly numbers and complete eradication of the local rodent reservoir, Rhombomys opimus, inside the camp during 2006 and 2007, respectively. ZCL attack rates decreased significantly (p < 0.0001), from 17.5% (14 cases/80 persons) for the 2005 German assessment teams to 0.087% (1 case/1150 persons) for the 2006 contingent, and 0% (0 cases) (p < 0.0001) for the 2007 contingent, with Quantified Infection Rates (QIRs) of 0.058, 0.0000055, and 0.0, respectively. Using QIR values, the protective factor of the integrated preventive measures was shown to be ≥10,545 times higher in the 2006 and 2007 contingents, compared with the 2005 assessment teams. Results show that the continuously implemented, integrated preventive techniques used in this study gave excellent and long-lasting protection against zoonotic cutaneous leishmaniasis under field conditions.