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Enzymes of the Golgi implicated in N-glycan processing are critical for brain development, and defects in many are defined as congenital disorders of glycosylation (CDG). Involvement of the Golgi mannosidase, MAN2A2 has not been identified previously as causing glycosylation defects.Exome sequencing of affected individuals was performed with Sanger sequencing of theWe identified a multiplex consanguineous family with a homozygous truncating variant p.Val1101Ter in MAN2A2. Lymphoblasts from two affected brothers carrying the same truncating variant showed decreases in complex N-glycans and accumulation of hybrid N-glycans. On testing of this variant in the developed complementation assay, we see the complete lack of complex N-glycans.Our findings show that pathogenic variants in MAN2A2 cause a novel autosomal recessive CDG with neurological involvement and facial dysmorphism. Here, we also present the development of a cell-based complementation assay to assess the pathogenicity of MAN2A2 variants, which can also be extended to MAN2A1 variants for future diagnosis.

BackgroundEnzymes of the Golgi implicated in N-glycan processing are critical for brain development, and defects in many are defined as congenital disorders of glycosylation (CDG). Involvement of the Golgi mannosidase, MAN2A2 has not been identified previously as causing glycosylation defects.MethodsExome sequencing of affected individuals was performed with Sanger sequencing of theMAN2A2transcript to confirm the variant. N-glycans were analysed in patient-derived lymphoblasts to determine the functional effects of the variant. A cell-based complementation assay was designed to assess the pathogenicity of identified variants using MAN2A1/MAN2A2 double knock out HEK293 cell lines.ResultsWe identified a multiplex consanguineous family with a homozygous truncating variant p.Val1101Ter in MAN2A2. Lymphoblasts from two affected brothers carrying the same truncating variant showed decreases in complex N-glycans and accumulation of hybrid N-glycans. On testing of this variant in the developed complementation assay, we see the complete lack of complex N-glycans.ConclusionOur findings show that pathogenic variants in MAN2A2 cause a novel autosomal recessive CDG with neurological involvement and facial dysmorphism. Here, we also present the development of a cell-based complementation assay to assess the pathogenicity of MAN2A2 variants, which can also be extended to MAN2A1 variants for future diagnosis.

PurposePlanning and implementing reconstruction projects in areas that are affected by conflict has proven to be far more challenging than expected and has often been considered to be inappropriate response from practitioners, aid agencies and government. Therefore, the purpose of this study is to explore reconstruction and development projects in Kosovo given its history of non-sovereign state under United Nations administration and analyse how they were planned and executed that would more likely yield progressive outcomes for the society.Design/methodology/approachThe study was designed to explore how projects are planned and implemented, as well as help in understanding the phenomena in the historical, social, cultural and governance context within the project implementation practices of multilateral agencies in Kosovo. Applying action research principles and using a detailed case study approach to the interviews, the study identified programme strengths, weaknesses and implications of project management practice and theory and differences of opinion within the project team in project planning and implementation in their wider sense.FindingsThere is evidence that both aid organisations’ constructed project management processes and international aid agencies practices do not work effectively in a community service delivery setting. The study showed that there continue to be challenges in project processes, implementation, stakeholder coordination, communication, cost, quality, procurement and risk management.Practical implicationsForward looking and grounded in traditions, the study indicated a need to promote a better understanding of how reconstruction and development projects are undertaken at all levels of the organisation and to describe processes, procedures and tools used for the actual application of projects in war-torn societies.Originality/valueThe study is among the first academic research worldwide to examine traditional practices of project management which are wildly applied and to explore if the same processes can be applied in post-conflict settings. This study is timely and beneficial in fulfilling its responsibility to post-conflict communities.

Purpose– Rehabilitation and reconstruction of social and economic infrastructure in a post-conflict environment are complex, long-debated issues in development cooperation. In addition to war creating large-scale human suffering, generating refugees, displacing populations, engendering psychological distress, obliterating infrastructure and transforming the economy, in post-conflict situations, deepening chaos and disorder can be found at the highest social, economic and political levels; serious developmental challenges remain insufficiently addressed. Repairing war-damaged infrastructure in order to reactivate the local economy is a challenge for all post-conflict countries. The paper aims to discuss these issues.Design/methodology/approach– The study was designed to examine planning and execution of post-conflict reconstruction (PCR). The use of a mixed-method research approach combining both quantitative and qualitative data collection was used to explore planning and implementation of PCR infrastructure projects in Kosovo. The data collection in the field was undertaken for a period of eight weeks, from July to September 2008. A total of 420 respondents were involved in the study process, as follows: key informants (four), pilot test (12), semi-structured interviews (36), project manager/engineers survey (231), chief of mission/country director survey (117), and focus group (20). To meet the needs of the society and recognise the required functional components of project management, the overall contexts of managing projects in a post-conflict environment have been discussed in the study.Findings– Planning and implementing reconstruction projects in areas affected by conflict have proven to be far more challenging than expected and responses by practitioners, aid agencies, and government regarded as inadequate. The changing political, economic, and social factors in Kosovo after the war in 1999 have had a significant influence on the limited adoption of a project management methodology in development and reconstruction projects. The findings from the exploratory study were aimed at improving understanding of the planning, pre-designing, and implementation of infrastructure projects. The findings indicated a need to promote a better understanding of how projects are undertaken at all levels of the organisation, and to describe processes, procedures, and tools used for the actual application of projects. The findings of the study identified a poor quality of planning and implementation of reconstruction projects in an environment of complexity, change, and uncertainty. The study also raised some very significant findings for a broader approach to community involvement in project identification, planning, and implementation. Infrastructure projects implemented in Kosovo were used to develop a conceptual framework for designing projects and programmes more likely to yield positive outcomes for post-conflict society.Originality/value– The study was done by the researcher in Kosovo.

The management of cardiac arrhythmias has changed dramatically over the past several years. New drugs and devices are now available to treat various arrhythmias. Many new agents have been developed that rely on different electrophysiologic mechanisms to elicit their effect on the heart rhythm. Though often effective, these drugs also pose a risk because all of them have a variety of potential adverse effects associated with their use. Many of these adverse reactions are common to all antiarrhythmic drugs, whereas others are unique to particular agents. This review discusses the notable adverse effects of selected antiarrhythmic drugs.