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To describe the genomic analysis and epidemiologic response related to a slow and prolonged methicillin-resistant Staphylococcus aureus (MRSA) outbreak.
Prospective observational study.
Neonatal intensive care unit (NICU).
We conducted an epidemiologic investigation of a NICU MRSA outbreak involving serial baby and staff screening to identify opportunities for decolonization. Whole-genome sequencing was performed on MRSA isolates.
A NICU with excellent hand hygiene compliance and longstanding minimal healthcare-associated infections experienced an MRSA outbreak involving 15 babies and 6 healthcare personnel (HCP). In total, 12 cases occurred slowly over a 1-year period (mean, 30.7 days apart) followed by 3 additional cases 7 months later. Multiple progressive infection prevention interventions were implemented, including contact precautions and cohorting of MRSA-positive babies, hand hygiene observers, enhanced environmental cleaning, screening of babies and staff, and decolonization of carriers. Only decolonization of HCP found to be persistent carriers of MRSA was successful in stopping transmission and ending the outbreak. Genomic analyses identified bidirectional transmission between babies and HCP during the outbreak.
In comparison to fast outbreaks, outbreaks that are “slow and sustained” may be more common to units with strong existing infection prevention practices such that a series of breaches have to align to result in a case. We identified a slow outbreak that persisted among staff and babies and was only stopped by identifying and decolonizing persistent MRSA carriage among staff. A repeated decolonization regimen was successful in allowing previously persistent carriers to safely continue work duties.
During a negotiation, there is seldom the time or capacity for parties to reach a full and complete agreement on a comprehensive legal framework for postconflict governance. Instead, the parties often agree to a preliminary set of principles coupled with a general governing framework. They then set forth an agreed process for negotiating, designing, and implementing a national dialogue, the drafting or amending of a constitution, and elections. This chapter explores the puzzle of whether and how to address constitutional modification during peace negotiations in a manner that promotes a durable peace. It reviews the peace processes related to conflicts in Bosnia and Herzegovina, Colombia, East Timor, Guatemala, Iraq, Kosovo, Macedonia, Nepal, Northern Ireland, Somalia, South Africa, Syria, and Yemen to explore whether and how to address constitutional modification during the peace process; the timing of determining and executing a postconflict constitution-drafting process; whether to draft an interim constitution; whether to accomplish constitutional reform through amendments or by drafting a full constitution; how to approve and finalize constitutional modifications; and whether and how to incorporate issues of human rights.
Self-determination and sovereignty-based conflicts are widespread throughout the globe, and are particularly durable and deadly. These conflicts may be resolved through military victory, through some form of enhanced internal self-determination, or through a path to external self-determination. This chapter explores the puzzle of whether and how to provide for external self-determination as a means for ensuring a durable peace. This chapter reviews the peace processes related to conflicts in Bosnia, Indonesia/East Timor, Israel/Palestine, Kosovo, Northern Ireland, Papua New Guinea/Bougainville, Serbia/Montenegro, Sudan/South Sudan, and Western Sahara in order to understand how the parties seek to most effectively share sovereignty in the interim; build sustainable institutions; determine final status; phase in the assumption of sovereignty; condition the assumption of this newfound sovereignty; and, if necessary, to constrain the exercise of sovereignty of the new state.
Nearly all contemporary conflicts are driven in part by political marginalization. This political marginalization amplifies the consequences of economic and cultural marginalization. To craft a durable peace, the parties to peace negotiations often spend considerable time and effort crafting power-sharing arrangements that balance the pull of some parties for greater diffusion and devolution of political power with the pull of other parties to maintain a degree of political centralization, for the sake of efficiency and effectiveness, and to preserve their prior political privileges. This chapter explores the puzzle of whether and how to create a vertical power-sharing arrangement that leads to a durable peace. It reviews the peace processes related to conflicts in Bosnia, Colombia, Indonesia/Aceh, Iraq, Macedonia, Nepal, the Philippines/Mindanao, South Africa, Sudan, and Yemen to understand how parties have grappled with the thorny set of conundrums, including the choice of state structure; the allocation of legislative and executive powers among the levels of government; the degree of political, administrative, and/or fiscal decision-making authority to be devolved; and the timeline for implementing any agreed plan for decentralization.
As the introduction notes, no corner of the globe is exempt from the scourge of deadly and durable armed conflict. Yet in the face of seemingly intractable conflicts, state and nonstate parties are time and again able to reach a negotiated compromise that leads to a durable peace. At other times, unfortunately, the process is rushed or misconceived and the peace is short-lived or never reached. In both cases, there are lessons to be learned with regard to how to solve the various puzzles and associated conundrums faced by parties seeking to design resilient peace agreements and establish a durable peace.
The need to rebuild the security infrastructure in a postconflict state is of paramount importance for ensuring a durable peace. This chapter examines the complicated tradeoffs parties face sharing and/or reestablishing the monopoly of force, including when sharing force with the international community; the questions of the consent of the state, and often the consent of the nonstate parties; the nature and configuration of the international forces, including the command structure of the international forces; and the mandate of those forces. The chapter also analyzes cases during which the state seeks to integrate nonstate armed actors into the national forces, when parties are faced with the questions of how best to provide for the disarmament, demobilization, and reintegration of nonstate forces, coupled with security sector reform for the national forces. The chapter additionally examines the questions that arise when the state seeks to restore limited control over the monopoly of force by permitting nonstate actors to come under the umbrella command of the national forces, including to what extent to promote some degree of integration among special units of the state and nonstate forces, as well as a timeline for the eventual integration of forces.
Access to natural resources and the allocation of revenue generated by resource exploitation is at the core of many conflicts and plays an important role in many others. Yet natural resources can also be a key factor in promoting a durable peace. This chapter explores the puzzle of whether and how to address natural resource ownership, management, and revenue allocation in a manner that promotes durable peace. This chapter reviews the peace processes related to conflicts in Papua New Guinea and Bougainville, Indonesia and Aceh, Iraq and Kurdistan, the Philippines and Bangsamoro, Sierra Leone, Sudan and South Sudan, Sudan and Darfur, and Yemen to understand if and when parties broach the subject of natural resources in the peace process, and how they then decide upon matters such as the ownership, management, and revenue allocation.
No corner of the globe is exempt from the scourge of conflict. Every year, hundreds of thousands of civilians die as a consequence of armed conflict, and millions more are displaced. These conflicts are brutal, durable, and global. Oftentimes, they are characterized by genocide, as in Bosnia, Darfur, Iraq (ISIS), Myanmar, and Rwanda, or widespread atrocity crimes, as in the Central African Republic, the Democratic Republic of Congo, Libya, Syria, and Yemen. As is often said, it is easy to start an armed conflict, but excruciatingly difficult to end one. In any given year, there are nearly four dozen active armed conflicts around the globe. While some of these conflicts may transpire over a relatively short time (3–5 years), others remain active for a decade or more, and still others are “frozen” for decades on end, continuing to contribute to instability and insecurity.
In all but the rarest circumstances, the world's deadly conflicts are ended not through outright victory, but through a series of negotiations. Not all of these negotiations, however, yield a durable peace. To successfully mitigate conflict drivers, the parties in conflict must address a number of puzzles, such as whether and how to share and/or re-establish a state's monopoly of force, reallocate the ownership and management of natural resources, modify the state structure, or provide for a path toward external self-determination. Successfully resolving these puzzles requires the parties to navigate a number of conundrums and make choices and design mechanisms that are appropriate to the particular context of the conflict, and which are most likely to lead to a durable peace. Lawyering Peace aims to help future negotiators build better and more durable peace agreements through a rigorous examination of how other parties have resolved these puzzles and associated conundrums.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.