Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low-or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI).Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression.

23 24 2 KRAB Zinc Finger Proteins (KZNFs) are the largest and fastest evolving family of 25 human transcription factors 1,2 . The evolution of this protein family is closely 26 linked to the tempo of retrotransposable element (RTE) invasions, with specific 27 KZNF family members demonstrated to transcriptionally repress specific families 28 of RTEs 3,4 . The competing selective pressures between RTEs and the KZNFs 29 results in evolutionary arms races whereby KZNFs evolve to recognize RTEs, 30 while RTEs evolve to escape KZNF recognition 5 . Evolutionary analyses of the 31 primate-specific RTE family L1PA and two of its KZNF binders, ZNF93 and 32 ZNF649, reveal specific nucleotide and amino changes consistent with an arms 33 race scenario. Our results suggest a model whereby ZNF649 and ZNF93 worked 34 together to target independent motifs within the L1PA RTE lineage. L1PA 35 elements eventually escaped the concerted action of this KZNF "team" over ~30 36 million years through two distinct mechanisms: a slow accumulation of point 37 mutations in the ZNF649 binding site and a rapid, massive deletion of the entire 38 ZNF93 binding site. 39 40KZNFs repress RTEs by recruiting the co-factor Kap1 (Trim28) which then recruits a 41 variety of repressive factors that establish heterochromatin 1,6 . We reasoned that KZNFs 42 expressed highly in the pluripotent stem cell (PSC) state were likely to be involved in arms 43 race scenarios as the pluripotent state is a high stakes evolutionary battleground since 44 RTEs that successfully retrotranspose in this state are inherited by all daughter cells 45 including the germ line 7 . We further narrowed our investigation to the L1PA RTE lineage, 46 which contains the only active, autonomous RTE family (L1HS elements) in humans, and is therefore likely to experience high evolutionary pressure for repression 8 . Recent ChIP-48 SEQ studies have revealed many KZNFs that bind L1PA families (Extended Data Fig 1), 49 although these studies were performed in an artificial overexpression context in 293T 50 cells 4,9 . In order to analyze which of these binders might be important for repression in 51 the PSC context, we mapped KZNF ChIP-SEQ data to consensus repeat elements via 52 the UCSC Repeat Browser (MH, in preparation), and then correlated Repeat Browser 53 "meta-peaks" with Kap1 ChIP-SEQ "meta-peaks" from PSCs ( Fig 1A). This analysis 54 identified two KZNFs, ZNF649 and ZNF93 which are highly expressed in the PSC state 55 (Extended Data Fig 1), as responsible for the majority of Kap1 recruit on L1PA elements 56 in the human PSC context. We previously identified ZNF93 as an important repressor of 57 L1PA elements in hPSCs, and traced its binding site to a 129-bp region that was deleted 58 in the youngest (L1PA2, L1HS) L1PA families 5 . Interestingly, ZNF649 recognition of L1PA 59 elements is strongest on L1PA6-L1PA4 elements, appears to weaken in younger 60 elements (L1PA3-L1PA2), and is unable to bind L1HS elements ( Fig 1A). Additionally, 61 the correlation between Kap1 binding...

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leucocyte antigen CD26, is considered to participate in T-cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses. In addition, the expression of CD25 (interleukin-2 receptor alpha chain) was evaluated to estimate the degree of T-cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD2-CD26-positive cells were reduced in patients compared with healthy controls [mean 40.2% (AN) and 41.1% (B) versus 47.4% (HC), P < 0.01], while the DPP IV activity in serum was elevated [mean 108.4 U/l (AN) versus 91.1 U/l (B) and 80.3 U/l (HC), P < 0.01]. The potential implications of our observations on, and beyond, immune function are discussed.

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