Explore the vast range of titles available.

Background: Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. Methods: In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. Results: During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups ( P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Child’s classification ( P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only ( P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. Conclusions: TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.

Over the past decade, splenic preservation has become a well-reported and accepted principle in trauma management. The reasons for splenic preservation may have influenced nontraumatic surgical management as well. To investigate the changing incidence and indications for splenectomy, we conducted a 10-year review of all splenectomies at our institution. During this time, between January 1, 1986, and December 31, 1995, 896 patients underwent splenectomy. Hospital charts and records were examined to determine the etiology and incidence of splenectomy. Indications were classified as: 1) trauma, i.e., performed for blunt or penetrating injury; 2) hematologic malignancy, i.e., therapy or staging of underlying leukemia, Hodgkin's lymphoma, or non-Hodgkin's lymphoma; 3) cytopenia, i.e., treatment of thrombocytopenia, anemia, or leukopenia; 4) iatrogenic, i.e., injury during another procedure; 5) incidental, i.e., required for adjacent organ resection; 6) portal hypertension, i.e., left-sided portal hypertension or during shunting procedure; 7) diagnostic, i.e., uncertainty excluding hematologic malignancy; or 8) other, i.e., miscellaneous indications. Trauma accounted for 41.5 per cent of all splenectomies during this time period, hematologic malignancy 15.4 per cent, cytopenia 15.6 per cent, incidental 12.3 per cent, iatrogenic 8.1 per cent, portal hypertension 2.3 per cent, diagnostic 2.0 per cent, and other 2.7 per cent. Comparing the first and second 5-year time periods, the following increases/decreases in average annual incidence were noted: splenectomy for all indications, -36.9 per cent; trauma, -32.9 per cent; hematologic malignancy, -51.4 per cent; cytopenia, 35.1 per cent; incidental, -35.9 per cent; iatrogenic, -30.2 per cent; diagnostic, +4.9 per cent, and other, -57 per cent. Traumatic injury to the spleen remains the most common indication for splenectomy, but the incidence has decreased dramatically over the past 10 years. Splenectomies for treatment of hematologic malignancies and cytopenia, as well as incidental and iatrogenic splenectomies, have also decreased significantly. Only the incidence of diagnostic splenectomy has remained stable. Although initiated within the field of trauma, the advantages of splenic preservation now appear to be well recognized beyond that field.

Hepatocellular carcinoma (HCC) in Western populations historically has been associated with poor survival. In this study, we conducted a 7-year retrospective analysis of patients evaluated at our institution with HCC to determine the effects of newer treatment strategies on outcome. During the period of study, 117 patients [86 (74%) male; mean age, 59 years (range, 16-85)] were evaluated with treatment as follows: surgical resection in 22 (19%), chemoembolization with or without systemic chemotherapy in 40 (35%), systemic treatment alone in 16 (13%), orthotopic liver transplantation in 8 (7%), and supportive care only in 31 (26%). Sixty-nine patients (59%) had documented cirrhosis, with hepatitis C being the most common cause in 27 of 69 (39%). In patients receiving no treatment, median survival was just under 3 months, with only two 1-year survivors. Patients with orthotopic liver transplantation had 1-, 2-, and 3-year survival rates of 87, 87, and 58 per cent compared with 69, 52, and 43 per cent in surgically resected patients. Survival after chemoembolization was 35, 20, and 11 per cent at 1, 2, and 3 years, whereas survival after systemic chemotherapy was 30 and 15 per cent at 1 and 2 years, respectively. One-year survival was improved in noncirrhotic patients compared with cirrhotics (47% vs 29%; P < 0.05) but was no different in patients younger than 55 years compared with older patients (38% vs 38%). When possible, surgical treatment strategies offer superior survival.

Bronchobiliary fistula is an uncommon but remarkable complication after hepatic resection. The case reported illustrates the clinical presentation and preferred initial management of these fistulae. A 61-year-old white male underwent two wedge resections for colorectal metastases to the liver with removal of a portion of the right diaphragm. Four years later, he developed obstructive jaundice secondary to tumor recurrence in the porta hepatis, which required endoscopic stent placement, radiation, and chemotherapy. Almost 2 years later, he developed frank biliptysis. Percutaneous transhepatic cholangiography (PTC) revealed occlusion of the common hepatic duct stent and a bronchobiliary fistula. With adequate reestablishment of common duct drainage, the patient rapidly improved and was discharged free of symptoms. Bronchobiliary fistulae are rare complications of hepatic resection that can present from days to years after operation. Endoscopic retrograde cholangiopancreatography and PTC are the diagnostic studies of choice and offer the possibility of therapeutic intervention. Although large series in the literature emphasize the surgical management of bronchobiliary fistulae, the reoperative procedures tend to be complicated, with a significant morbidity and mortality. Nonsurgical interventions via endoscopic retrograde cholangiopancreatography or PTC are more recently notably successful when resolution of a distal biliary obstruction is accomplished. Only after aggressive attempts at nonoperative, interventional techniques have failed should operative approaches be entertained.

The spread of farming from western Asia to Europe had profound long-term social and ecological impacts, but identification of the specific nature of Neolithic land management practices and the dietary contribution of early crops has been problematic. Here, we present previously undescribed stable isotope determinations of charred cereals and pulses from 13 Neolithic sites across Europe (dating ca . 5900–2400 cal B.C.), which show that early farmers used livestock manure and water management to enhance crop yields. Intensive manuring inextricably linked plant cultivation and animal herding and contributed to the remarkable resilience of these combined practices across diverse climatic zones. Critically, our findings suggest that commonly applied paleodietary interpretations of human and herbivore δ ¹⁵N values have systematically underestimated the contribution of crop-derived protein to early farmer diets.

BackgroundWomen remain underrepresented in academic medicine, particularly in leadership positions. This lack of women in leadership has been shown to have negative implications for both patient care and educational outcomes. Similarly, the literature demonstrates that female physicians are less likely to have mentors, despite the proven benefits of mentorship for career advancement. The objective of this review is to identify and describe models of mentorship for women in academic medicine.MethodsWe searched PubMed, PsycINFO, Education Resources Information Center, and Cochrane Databases of Systematic Reviews following PRISMA guidelines in June 2017. We included original English language studies that described a mentorship program in the USA that involved academic medical doctorates and that were created for women or provided results stratified by gender.ResultsOur search returned 3625 results; 3309 references remained after removal of duplicates. Twenty articles met inclusion criteria. The majority of the programs were designed for junior faculty and used the dyad model of mentoring (i.e., one mentor/one mentee). Frequently cited objectives of these programs were to improve scholarship, promotion, and retention of female faculty. Program evaluations were primarily survey-based, with participant-reported satisfaction being the most frequent measured outcome. Most results showed very high satisfaction. Gender concordance between mentor and mentee did not impact satisfaction. Eight articles reported objective outcomes, including publications, retention, and promotion, and each of these demonstrated an improvement after program implementation.DiscussionOur review suggests that mentorship programs designed for women, regardless of the model, are met with high satisfaction and can help promote and retain women in academic medicine. No clear best practices for mentorship emerged in the literature. Institutions, therefore, can individualize their mentorship programs and models to available resources and goals. These results demonstrate the importance of more widespread implementation of mentorship programs to more effectively facilitate professional development and success of women in academic medicine.

Arrays of heaving buoy type wave energy converters (WECs) are a promising contender to harness the renewable power of ocean waves on a commercial scale but require strategies to achieve efficient capture of wave energy over broad frequency bands for economic viability. A WEC-array design is proposed for absorption over a target frequency range in the two-dimensional water wave context by spatially grading the resonant properties of WECs via linear spring–damper power take-off mechanisms. The design is based on theories for rainbow reflection and rainbow absorption, which incorporate analyses based on Bloch wave modes and pole–zero pairs in complex frequency space. In contrast to previous applications of these theories, the influence of a higher-order passband and associated pole–zero pairs are shown to influence absorption at the high-frequency end of the target interval. The theories are used to inform initialisations for optimisation algorithms, and an optimised array of only five WECs is shown to give near-perfect absorption ($\\geq$99 %) over the target interval. Broadband absorption is demonstrated when surge and pitch motions are released, for irregular sea states, and for incident wave packets in the time domain, where the time-domain responses are decomposed into Bloch modes to connect with the underlying theory.

Applicatives of unaccusatives provide a crucial test case for the inherent- case view of ergativity. If ergative is assigned only to external arguments, in their θ-positions, there can be no “raising to ergative” in applicative unaccusatives; an internal argument subject can never receive ergative case. In this article, I present evidence from Nez Perce (Sahaptian) that this prediction is false. In Nez Perce applicative unaccusatives, the theme argument raises over the applicative argument and is accordingly marked with ergative case. Nez Perce thus demonstrates raising to ergative. Departing from Baker’s (2014) conclusions for similar phenomena in Shipibo (Panoan), I argue that apparently nonlocal movement of the theme in the raising-to-ergative pattern involves not a covert adpositional structure, but rather a response to independently motivated constraints on antilocal movement and remnant movement.

Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N(ε)-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N(ε)-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors. High-throughput screening of a ∼236,000-member collection of diverse molecules arrayed as dilution series was used to identify inhibitors of the JMJD2 (KDM4) family of 2-oxoglutarate-dependent histone demethylases. Initial screening hits were prioritized by a combination of cheminformatics, counterscreening using a coupled assay enzyme, and orthogonal confirmatory detection of inhibition by mass spectrometric assays. Follow-up studies were carried out on one of the series identified, 8-hydroxyquinolines, which were shown by crystallographic analyses to inhibit by binding to the active site Fe(II) and to modulate demethylation at the H3K9 locus in a cell-based assay. These studies demonstrate that diverse compound screening can yield novel inhibitors of 2OG dependent histone demethylases and provide starting points for the development of potent and selective agents to interrogate epigenetic regulation.

BackgroundThough the USA is becoming increasingly diverse, the physician workforce contains a disproportionately low number of physicians from racial and ethnic groups that are described as underrepresented in medicine (URiM). Mentorship has been proposed as one way to improve the retention and experiences of URiM physicians and trainees. The objective of this systematic review was to identify and describe mentoring programs for URiM physicians in academic medicine and to describe important themes from existing literature that can aid in the development of URiM mentorship programs.MethodsThe authors searched PubMed, PsycINFO, ERIC, and Cochrane databases, and included original publications that described a US mentorship program involving academic medical doctors at the faculty or trainee level and were created for physicians who are URiM or provided results stratified by race/ethnicity.ResultsOur search yielded 4,548 unique citations and 31 publications met our inclusion criteria. Frequently cited objectives of these programs were to improve research skills, to diversify representation in specific fields, and to recruit and retain URiM participants. Subjective outcomes were primarily participant satisfaction with the program and/or work climate. The dyad model of mentoring was the most common, though several novel models were also described. Program evaluations were primarily subjective and reported high satisfaction, although some reported objective outcomes including publications, retention, and promotion. All showed satisfactory outcomes for the mentorship programs.DiscussionThis review describes a range of successful mentoring programs for URiM physicians. Our recommendations based on our review include the importance of institutional support for diversity, tailoring programs to local needs and resources, training mentors, and utilizing URiM and non-URiM mentors.