Does local implantation of gentamicin impair renal function in patients undergoing surgery for chronic bone infection?

Background: The treatment of chronic bone infection often involves excision of dead bone and implantation of biomaterials which elute antibiotics. Gentamicin is a preferred drug for local delivery, but its systemic use carries a well-established risk of nephrotoxicity.  We aim to establish the risk of acute kidney injury (AKI) with local delivery in a ceramic carrier.Methods: 163 patients with Cierny-Mader type 3 or 4 chronic osteomyelitis had a single-stage operation including filling of the osseous defect with a calcium sulphate-hydroxyapatite carrier containing gentamicin. Mean gentamicin dosing was 191.3 mg (maximum 525 mg). Glomerular filtration rate (GFR) was calculated pre-operatively and during the first seven days post-operatively. Renal impairment was graded using the chronic kidney disease (CKD) staging system, and AKI was assessed using the RIFLE criteria.Results: 155 cases had adequate data to allow calculation of pre- and post-operative GFR. 7 had pre-existing renal disease. 70 patients (45.2%) had a temporary GFR drop post-operatively, with the greatest decrease occurring at a mean of 3.06 days following surgery. Twenty cases had a >10% decline in GFR, but 12 resolved within 7 days. 7 patients transiently fell into the “Risk” category according to RIFLE criteria, but no patient had a change consistent with “Injury”, “Failure” or “Loss” of renal function and none had clinical signs of new acute renal impairment post-operatively. Conclusions: Renal function is not significantly affected by local implantation of gentamicin up to 525 mg. The presence of pre-existing renal disease is not a contraindication to local gentamicin therapy.

Economic Growth or Stagnation during the Interwar Period: Reconstruction of Cypriot GDP 1921-1938

This paper explores the macro-economic history of Cyprus in the inter-war period. It constructs the first detailed estimates of output at aggregate and sector levels, enabling the analysis of economic growth and the sectoral structure of the island’s economy. It evaluates its performance within the context of economic change on Europe’s South Eastern periphery and, specifically, in light of the experience of British colonial rule. The thesis argues, first, that economic growth was slow in wider European comparison and as sluggish as in neighbouring countries. It was so despite the island being far less exposed to the political upheavals of the First World War than most other economies in South Eastern Europe. Cyprus experienced a prolonged agricultural crisis, but participated in the post-depression recovery through the growth in international demand for the output of its copper mining industry. The colonial government remained committed to balanced budgets and non-intervention in the economy, limiting their ability to combat the effects of the great depression. As a result, the deteriorating economic situation increased the political tension between the islanders and the colonial government. The reluctance to mount an effective policy response to the great depression acted as a catalyst to political polarization, leading to violence and the suspension of the island’s constitution

A Tribute to William S. Geimer

A Tribute to William S. Geimer Meredith Susan Palmer* * Associate Dean for Student Affairs and Admissions, Washington and Lee University School of Law, J.D., 1985, Washington and Lee University. Truly, I say to you, as you did it to one of the least of these my brethren, you did it to me.1 Bill Geimer is not a man of material things. But somehow, in the material things that he chose to have around him - the mementos, the odd souvenirs, the offerings from students, clients, friends - I find the story of the man, the teacher, and the lawyer Bill Geimer is to me. In my mind's eye, I see Bill's office here at Washington and Lee as I first saw it, as a hesitant first-year law student approaching the sanctum sanctorum of a faculty member. There is a desktop name plate, regular Army issue, decorated with grenades or something equally militaristic and intimidating. But next to that is a picture of Dr. Martin Luther King, with his stirring words evoking hope for justice and freedom on earth. And next to that, a membership certificate for the Lawyer's Alliance for Nuclear Arms Control, and a drawing of Quijote, lance raised to a windmill. How could this be? While reconciling the seemingly irreconcilable is the everyday task of the law student, no trick of logic could make these disparate pieces fit; one simply had to get to know the man. That one could do so as a law student is itself part of what defines Bill Geimer. The student who came to know Bill heard a story of a kid from the rural south, off to a small state university to play basketball but who, like countless kids before him, spent a bit more time playing than studying. Come Graduation Day, with no game plan, he joined Uncle Sam's family. A grounding in tanks, guns, and tactics preceded duty with the military police, but something else happened during those years. Assigned to assist with an investigation, he finds an aptitude for the law, an appreciation of justice, and a burning sense of the unfairness of justice denied. The young man who returned from service to go on to a distinguished career as a law student at the University of North Carolina was a man with a game plan, and a mission. It was no surprise that Bill's mission as a lawyer was not in the office towers of Atlanta or the corporate boardrooms of Wall Street, but among the plain folks of Fayetteville, North Carolina, and later in the community of migrant farm labor working and living hard under the hot Carolina sun. I see another memento, this time in Bill's home. It's an odd piece of, well, let's call it folk art. Crudely carved, frankly ugly. Taste is a delicate thing, so one observes diplomatically that it is an "interesting" object. There's a story, of course, a story of a client for whom Bill had worked, putting together the paperwork to get a fledgling arts-and-crafts shop off the ground. This client, like many Bill served, claimed not to have the cash to pay. But, the client said, he could give Bill this valuable piece of work. Barter being a fundamentally more honest exchange and thus appealing to Bill, the transaction was concluded. Not until Bill brought his sculpture home did he discover the price tag stuck to the underside, for something substantially less than the agreed-upon fee. He kept the awkward thing, price tag intact, I think as a reminder of his own fallibility, of the ingenuity of the ordinary man, and of the need to forget neither. Another memento, in some ways the most important to this former student, is a large, faded, well-handled poster on the professor's office door. A young man in Carolina Blue goes up for a shot, stretching for the basket, with seconds left on the clock. Anyone who knows Bill Geimer knows that he is devoted to Carolina basketball. In fact, Bill may have spent so much time watching the Tar Heels play that he began to confuse teaching with coaching. As a former student of Bill's, I'm not sure that was a bad thing.

Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study

Introduction: Molecular markers that predict responses to particular therapies are invaluable for optimization of patient treatment. The TRYPHAENA study showed that pertuzumab and trastuzumab with chemotherapy was an efficacious and tolerable combination for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the neoadjuvant setting. We analyzed whether particular biomarkers correlated with the responses observed and therefore may predict outcomes in patients given pertuzumab plus trastuzumab. Methods: We describe the analysis of a panel of biomarkers including HER2, human epidermal growth factor receptor 3 (HER3), epidermal growth factor receptor (EGFR), phosphatase and tensin homolog (PTEN), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) by qRT-PCR, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), enzyme-linked immunosorbent assay (ELISA), and PCR-based mutational analyses as appropriate. For each marker analyzed, patients were categorized into ‘low’ (generally below median) or ‘high’ (generally above median) subgroups at baseline and post-treatment. Results: Correlation of marker subgroups with the achievement of a pathological complete response (pCR) (ypT0/is) was analyzed. HER2 protein and mRNA expression levels were associated with pCR rate in two of the three study arms and the pooled analyses. Correlations of biomarker status with pCR occurred in one individual arm only and the pooled analyses with EGFR and PTEN; however, interpretation of these results is limited by a strong imbalance in patient numbers between the high and low subgroups and inconsistency between arms. We also found no association between expression levels of TOP2A and pCR rate in either the anthracycline-containing or free arms of TRYPHAENA. Conclusions: According to these analyses, and in line with other analyses of pertuzumab and trastuzumab in the neoadjuvant setting, we conclude that HER2 expression remains the only marker suitable for patient selection for this regimen at present. Trial registration: The TRYPHAENA study was registered with ClinicalTrials.gov, NCT00976989, on September 14 2009

Right ventricular outflow reconstruction with cryopreserved homografts in pediatric patients: Intermediate-term follow-up with serial echocardiographic assessment

AbstractObjectives. This study was performed to assess by echocardiography the intermediate-term outcome of cryopreserved homografts employed in pulmonary outflow reconstruction in children and to validate the reliability of Doppler echocardiography in their evaluation.Background. Cryopreserved homografts have become the most widely used pulmonary conduits. Previous reports have shown the occurrence of homograft regurgitation in the immediate postoperative period and the propensity of regurgitation to progress. Although Doppler echocardiography has been useful in assessing extracardiac valved conduit stenosis, its reliability in assessing a large series of cryopreserved homografts has not been documented.Methods. Echocardiograms of 41 patients (43 homografts) who underwent operations between December 1986 and October 1992 were retrospectively reviewed. The median age of patients at operation was 37.5 months (range 3 to 333), and the median duration of follow-up was 28.5 months (range 1 to 68). Homograft regurgitation was classified on a scale of 0 to 4+. Pressure gradients across the homografts measured in 23 catheterizations were correlated with corresponding echocardiographic gradients.Results. Regurgitation: Homograft regurgitation occurred in 100% of patients at follow-up. Progression of severity >2 grades occurred during follow-up in 35% and was associated with operation before age 18 months (p < 0.002) and stenosis progression (p < 0.05) but not with homograft type (aortic or pulmonary). These data predict that 50% of patients operated on before 18 months of age will have severe regurgitation by 15 months postoperatively compared with only 15% operated on after 18 months. Stenosis: At follow-up, 51% of homografts had a stenotic gradient ≥25 mm Hg predominantly at the distal anastomosis, and stenosis progression was related to young age at operation (<18 months, p < 0.005) and small conduit size (p < 0.01). Fifty percent of conduits implanted before age 18 months could be predicted to stenose by 21.8 months compared with only 5% of those implanted after age 18 months. The gradient measured from Doppler echocardiography correlated well with the catheterization gradient (r = 0.86).Conclusions. Cryopreserved homograft dysfunction is frequent and progressive. Young age at operation (<18 months) predicts more rapid deterioration. Doppler echocardiography is reliable in assessing the systolic gradients across homografts. Serial echocardiographic assessment in the follow-up of these patients accurately characterizes these problems

A robust preference for cheap-and-easy strategies over reliable strategies when verifying personal memories

People depend on various sources of information when trying to verify their autobiographical memories. Yet recent research shows that people prefer to use cheap-and-easy verification strategies, even when these strategies are not reliable. We examined the robustness of this cheap strategy bias, with scenarios designed to encourage greater emphasis on source reliability. In three experiments, subjects described real (Experiments 1 and 2) or hypothetical (Experiment 3) autobiographical events, and proposed strategies they might use to verify their memories of those events. Subjects also rated the reliability, cost, and the likelihood that they would use each strategy. In line with previous work, we found that the preference for cheap information held when people described how they would verify childhood or recent memories (Experiment 1); personally-important or trivial memories (Experiment 2), and even when the consequences of relying on incorrect information could be significant (Experiment 3). Taken together, our findings fit with an account of source monitoring in which the tendency to trust one’s own autobiographical memories can discourage people from systematically testing or accepting strong disconfirmatory evidence

The Genomic Signature of Crop-Wild Introgression in Maize

The evolutionary significance of hybridization and subsequent introgression has long been appreciated, but evaluation of the genome-wide effects of these phenomena has only recently become possible. Crop-wild study systems represent ideal opportunities to examine evolution through hybridization. For example, maize and the conspecific wild teosinte Zea mays ssp. mexicana, (hereafter, mexicana) are known to hybridize in the fields of highland Mexico. Despite widespread evidence of gene flow, maize and mexicana maintain distinct morphologies and have done so in sympatry for thousands of years. Neither the genomic extent nor the evolutionary importance of introgression between these taxa is understood. In this study we assessed patterns of genome-wide introgression based on 39,029 single nucleotide polymorphisms genotyped in 189 individuals from nine sympatric maize-mexicana populations and reference allopatric populations. While portions of the maize and mexicana genomes were particularly resistant to introgression (notably near known cross-incompatibility and domestication loci), we detected widespread evidence for introgression in both directions of gene flow. Through further characterization of these regions and preliminary growth chamber experiments, we found evidence suggestive of the incorporation of adaptive mexicana alleles into maize during its expansion to the highlands of central Mexico. In contrast, very little evidence was found for adaptive introgression from maize to mexicana. The methods we have applied here can be replicated widely, and such analyses have the potential to greatly informing our understanding of evolution through introgressive hybridization. Crop species, due to their exceptional genomic resources and frequent histories of spread into sympatry with relatives, should be particularly influential in these studies

Drugless and radiographer led: the start of a new era for CT coronary angiography

Objective. Since inception CT coronary angiography (CTCA) has required facilitating beta blockers (BB). However, CT technology has improved rapidly as has radiographer and reporter expertise. Using these factors, we instituted a radiographer led cardiac CT service (RLCCTS), without routine BB, which we studied for quality control (QC). Methods. RLCCTS started October 2021 using a wide detector array CT system, with 20 min slots. QC study was registered with the clinical audit team, University Hospitals Plymouth, CA_2020-21-118. Uniform reporting was agreed including indication, BB administration, demographics, dose length product (DLP) and the coronary artery disease—reporting and data system (CAD-RADS) score. Uncertain CAD-RADS meant a non-diagnostic scan (NDS). Six months of data were collected; stable chest pain (SCP) patients, who have national CTCA QC comparators, were analysed using descriptive statistics. Results. Of 1475 patients, 447 were not SCP patients—known CAD (157); valves (286); removed (4, data incomplete) leaving 1028 SCP patients CTCA for analysis. Demographics—mean age 63 years, body mass index 29, 50.4% women. BB therapy—four patients (two recalls). Overall, 36/1024 or 3.5% were NDS; median DLP 173mGy×cm; mean heart rate (HR) 70 bpm, 99/1024 or 9.7% HR \u3e90 bpm (45% not sinus rhythm). Conclusions. Quality for RLCCTS was judged by NDS rate and DLP. National QC comparators suggest 4% NDS rate; median DLP for SCPP CTCA 209 mGy×cm. RLCCTS compares favourably. With modern cardiac CT, experienced radiographers and reporters, ‘drugless’ RLCCTS can deliver 20 min slot CTCA with satisfactory QC indicators