Declining liver graft quality threatens the future of liver transplantation in the United States

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of "opt-out" organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level

Remarks on Semileptonic B and D Decays into Orbitally Excited Mesons

We have obtained the differential decay rate and calculated the branching ratios of the exclusive semileptonic decays $B(D) \to Xl\nu$, where $X$ is a p-wave meson, using the nonrelativistic ISGW quark model. Our results are compared with the predictions of the ISGW2 model. We have computed some branching ratios that were not reported or were reported with 0.00 in this model. For example, we find that $Br(B_c^- \to \bar{B_{s2}^{*0}}l^-\bar{\nu}) = 4.03 \times 10^{-5}$, $Br(B_c^- \to \bar{B_2^{*0}}l^- \bar{\nu}) =3.65 \times 10^{-6}$ and $Br(D_s^+ \to f_2l^+\nu) = 2.7 \times 10^{-5}$, which seems to be at the reach of forthcoming experiments. Furthermore, we have classified the $B_{u,d,s} \to Tl\nu$ decays in two groups and compared the semileptonic and nonleptonic decays including a tensor meson in the final state.Comment: 11 pages, LaTe

Rational F-Theory GUTs without exotics

We construct F-theory GUT models without exotic matter, leading to the MSSM matter spectrum with potential singlet extensions. The interplay of engineering explicit geometric setups, absence of four-dimensional anomalies, and realistic phenomenology of the couplings places severe constraints on the allowed local models in a given geometry. In constructions based on the spectral cover we find no model satisfying all these requirements. We then provide a survey of models with additional U(1) symmetries arising from rational sections of the elliptic fibration in toric constructions and obtain phenomenologically appealing models based on SU(5) tops. Furthermore we perform a bottom-up exploration beyond the toric section constructions discussed in the literature so far and identify benchmark models passing all our criteria, which can serve as a guideline for future geometric engineering.Comment: 27 Pages, 1 Figur

Non-supersymmetric heterotic model building

We investigate orbifold and smooth Calabi-Yau compactifications of the non-supersymmetric heterotic SO(16)xSO(16) string. We focus on such Calabi-Yau backgrounds in order to recycle commonly employed techniques, like index theorems and cohomology theory, to determine both the fermionic and bosonic 4D spectra. We argue that the N=0 theory never leads to tachyons on smooth Calabi-Yaus in the large volume approximation. As twisted tachyons may arise on certain singular orbifolds, we conjecture that such tachyonic states are lifted in the full blow-up. We perform model searches on selected orbifold geometries. In particular, we construct an explicit example of a Standard Model-like theory with three generations and a single Higgs field.Comment: 1+30 pages latex, 11 tables; v2: references and minor revisions added, matches version published in JHE

Addressing Global Ruminant Agricultural Challenges Through Understanding the Rumen Microbiome: Past, Present, and Future

The rumen is a complex ecosystem composed of anaerobic bacteria, protozoa, fungi, methanogenic archaea and phages. These microbes interact closely to breakdown plant material that cannot be digested by humans, whilst providing metabolic energy to the host and, in the case of archaea, producing methane. Consequently, ruminants produce meat and milk, which are rich in high-quality protein, vitamins and minerals, and therefore contribute to food security. As the world population is predicted to reach approximately 9.7 billion by 2050, an increase in ruminant production to satisfy global protein demand is necessary, despite limited land availability, and whilst ensuring environmental impact is minimized. Although challenging, these goals can be met, but depend on our understanding of the rumen microbiome. Attempts to manipulate the rumen microbiome to benefit global agricultural challenges have been ongoing for decades with limited success, mostly due to the lack of a detailed understanding of this microbiome and our limited ability to culture most of these microbes outside the rumen. The potential to manipulate the rumen microbiome and meet global livestock challenges through animal breeding and introduction of dietary interventions during early life have recently emerged as promising new technologies. Our inability to phenotype ruminants in a high-throughput manner has also hampered progress, although the recent increase in "omic" data may allow further development of mathematical models and rumen microbial gene biomarkers as proxies. Advances in computational tools, high-throughput sequencing technologies and cultivation-independent "omics" approaches continue to revolutionize our understanding of the rumen microbiome. This will ultimately provide the knowledge framework needed to solve current and future ruminant livestock challenges.</p

Trends in Characteristics of Patients Listed for Liver Transplantation Will Lead to Higher Rates of Waitlist Removal Due to Clinical Deterioration

BACKGROUND: Changes in the epidemiology of end-stage liver disease may lead to increased risk of dropout from the liver transplant waitlist. Anticipating the future of liver transplant waitlist characteristics is vital when considering organ allocation policy. METHODS: We performed a discrete event simulation to forecast patient characteristics and rate of waitlist dropout. Estimates were simulated from 2015 to 2025. The model was informed by data from the Organ Procurement and Transplant Network, 2003 to 2014. National data are estimated along with forecasts for 2 regions. RESULTS: Nonalcoholic steatohepatitis will increase from 18% of waitlist additions to 22% by 2025. Hepatitis C will fall from 30% to 21%. Listings over age 60 years will increase from 36% to 48%. The hazard of dropout will increase from 41% to 46% nationally. Wait times for transplant for patients listed with a Model for End-Stage Liver Disease (MELD) between 22 and 27 will double. Region 5, which transplants at relatively higher MELD scores, will experience an increase from 53% to 64% waitlist dropout. Region 11, which transplants at lower MELD scores, will have an increase in waitlist dropout from 30% to 44%. CONCLUSIONS: The liver transplant waitlist size will remain static over the next decade due to patient dropout. Liver transplant candidates will be older, more likely to have nonalcoholic steatohepatitis and will wait for transplantation longer even when listed at a competitive MELD score. There will continue to be significant heterogeneity among transplant regions where some patients will be more likely to drop out of the waitlist than receive a transplant

Organizational decision‐making during COVID‐19: A qualitative analysis of the organizational decision‐making system in the United States during COVID‐19

This study sought to understand COVID‐19‐related organizational decisions were made across sectors. To gain this understanding, we conducted semi‐structured interviews with organizational decision‐makers in North Carolina about their experiences responding to COVID‐19. Conventional content analysis was used to analyse the context, inputs, and processes involved in decision‐making. Between October 2020 and February 2021, we interviewed 44 decision‐makers from the following sectors: business ( n = 4), community non‐profit ( n = 3), county government ( n = 4), healthcare ( n = 5), local public health ( n = 5), public safety ( n = 7), religious ( n = 6), education ( n = 7) and transportation ( n = 3). We found that during the pandemic, organizations looked to scientific authorities, the decisions of peer organizations, data about COVID‐19, and their own experience with prior crises. Interpretation of inputs was informed by current political events, societal trends, and organization mission. Decision‐makers had to account for divergent internal opinions and community behaviour. To navigate inputs and contextual factors, organizations decentralized decision‐making authority, formed auxiliary decision‐making bodies, learned to resolve internal conflicts, learned in real time from their crisis response, and routinely communicated decisions with their communities. In conclusion, aligned with systems and contingency theories of decision‐making, decision‐making during COVID‐19 depended on an organization's ‘fit’ within the specifics of their existing system and their ability to orient the dynamics of that system to their own goals

Colorectal adenomas contain multiple somatic mutations that do not coincide with synchronous adenocarcinoma specimens

We have performed a comparative ultrasequencing study of multiple colorectal lesions obtained simultaneously from four patients. Our data show that benign lesions (adenomatous or hyperplastic polyps) contain a high mutational load. Additionally multiple synchronous colorectal lesions show non overlapping mutational signatures highlighting the degree of heterogeneity between multiple specimens in the same patient. Observations in these cases imply that considering not only the number of mutations but an effective oncogenic combination of mutations can determine the malignant progression of colorectal lesions