Late Occurrence Research Articles

The late Early Pleistocene flora of Oriolo, Faenza (Italy): assembly of the modern forest biome

The late Early Pleistocene was the last time of equable climate in northern Central Italy, reflected in its large mammal fauna and numerous palynological records. Reliably dated leaf fossils from this time are rare, but provide crucial information on local and regional vegetation, biogeographic relationships, and species turnover coinciding with the assembly of modern forest biomes. Here we investigated a rich assemblage of leaf and fruit impressions (63 fossil-taxa) from the Oriolo quarry, Faenza (Ravenna), dated to the latest Calabrian, preserved in transgressive coastal deposits. The fossil assemblage represents riparian vegetation and xeric alluvial habitats in the lowlands and forest vegetation above the alluvial plain. Forest-building trees were deciduous, but comprised several taxa characteristic of open scrubland or forest edges. The composition of the flora reflects a dynamic process of assembling modern forest biomes in western Eurasia. While most taxa correspond to modern submediterranean and temperate woody species, some others represent late occurrences of taxa today confined to refugia outside Italy (Parrotia, Gleditsia, Pterocarya), and a few are Miocene/Pliocene relics indicating final floristic links with East Asia (Japan) and/or North America (Tsuga cf. chiarugii, Carya cf. minor) and Pleistocene endemism in Italy (Berberis auriolensis, Acer aemilianum).

Pre-Birth and Early-Life Factors Associated With the Timing of Adiposity Peak and Rebound: A Large Population-Based Longitudinal Study.

Background: The late occurrence of adiposity peak (AP) and the early occurrence of adiposity rebound (AR) are considered the earliest indicators for obesity and its related health conditions later in life. However, there is still limited information for their upstream factors. Therefore, in this study, we aimed to identify the parental and child factors associated with the timing of AP and AR in the early stage of life.Methods: This is a population-based longitudinal study conducted in Shanghai, China. The BMI data of children born between September 2010 and October 2013 were followed from birth to 80 months. Subject-specific body mass index trajectories were fitted by non-linear mixed-effect models with natural cubic spline functions, and the individual's age at AP and AR was estimated. The generalized linear regression models were applied to identify the upstream factors of late occurrence of AP and early occurrence AR.Results: For 7,292 children with estimated AP, boys were less likely to have a late AP [adjusted risk ratio (RR) = 0.83, 95% confidence interval (CI): 0.77–0.90, p < 0.001], but preterm born children had a higher risk of a late AP (adjusted RR = 1.25, 95% CI: 1.07–1.47, p < 0.01). For 10,985 children with estimated AR, children with breastfeeding longer than 4 months were less likely to have an early AR (adjusted RR = 0.80, 95% CI: 0.73–0.87, p < 0.001), but children who were born to advanced-age mothers and who were born small for gestational age had a higher risk of having an early AR (adjusted RR = 1.21, 95% CI: 1.07–1.36, p < 0.01; adjusted RR = 1.20, 95% CI: 1.04–1.39, p = 0.01).Conclusions: Modifiable pre-birth or early-life factors associated with the timing of AP or AR were found. Our findings may help develop prevention and intervention strategies at the earliest stage of life to control later obesity and the health conditions and diseases linked to it.

Timing to Carotid Endarterectomy Affects Early and Long Term Outcomes of Symptomatic Carotid Stenosis.

The aim of this study is to evaluate early and long-term outcomes according to the timing to carotid endarterectomy (CEA) of symptomatic carotid stenosis. Consecutive CEAs with selective shunting for symptomatic carotid stenosis ≥50% performed between 2009 and 2020. Patients had acute neurological impairment on presentation, defined as <5 points on the National Institutes of Health Stroke Scale (NIHSS). We grouped patients according to time between index event and CEA: the first group was operated between 0 and 2 days, the second group between 3 and 7 days, the third group between 8 and 14 days and the last group after 15 days. Thirty-day neurological status improvement was defined as a decrease (≥1) in the 30-day NIHSS score versus NIHSS score immediately before surgery. Five hundred CEAs were performed. The perioperative combined stroke and mortality rate was 3.6% (18/500), representing a perioperative mortality rate of 0.2 (n=1) and stroke rate of 3.4% (n=17). Overall freedom from stroke was 95% at 1 year, 89 % at 6 years, and 88% at 10 years. Annual stroke rate was 0.6% after the 30-day period. Thirty-day improvement in neurologic status occurred in 103 patients (20.6%), while in 380 (76%) neurologic status was unchanged, and 17 (3.4%) experienced worsening of their neurologic status. Patients treated within 7 days from the index event had significant benefit (OR=2.6) in the 30-day neurological improvement versus those treated after 7 days from the index event. Timing to CEA <2 days increased significantly the risk of late stroke (OR=9.7). The ideal timing for performing CEA is between 3 and 7 days from the index event if NIHSS <5 as it is associated with the best rates of improvement in neurological status and durability in the long term. Very early CEA (<48 hrs) was associated with increased late stroke occurrence.

Comparison of treatment outcomes of pelvis external radiotherapy with and without vaginal brachytherapy for cervical cancer patients with positive or close vaginal resected margins.

We evaluated whether there is a difference in the local recurrence and survival after pelvic external radiotherapy (ERT) with and without boost vaginal brachytherapy (VB) in cervical cancer patients with positive or close vaginal resected margins (RM). We retrospectively reviewed FIGO stage IA-IIB cervical cancer patients treated with postoperative ERT between 1997 and 2018. The sixty patients showing close (safety margin < 5mm) or positive vaginal RM were included. ERT was delivered with median 50.4Gy in 28 fractions to the pelvis and VB with median 30Gy in 6 fractions. The median follow-up duration was 46months. Five out of 30 patients treated with ERT alone experienced vaginal recurrence within 2years after surgery. The 5-year local control (LC) was 100% in patients receiving ERT + VB compared with 81.3% in patients receiving ERT alone (log rank p = 0.022). The 5-year pelvic control (PC) was 95.8% for patients receiving ERT + VB and 76.8% for ERT alone (p = 0.041). The 5-year overall survival and recurrence-free survival (RFS) were not significantly different between treatment groups. In multivariate analysis, perineural invasion was a significant risk factor for PC (p = 0.024). Parametrial involvement (p = 0.044) and vascular invasion (p = 0.032) were unfavorable prognostic factors for RFS. Late toxicity occurrences were not significant in both groups. VB after ERT improved LC and PC in cervical cancer patients with close or positive RM after hysterectomy. The toxicities were not increased after VB was added to ERT.

An Early Pleistocene hippopotamus from Westbury Cave, Somerset, England: support for a previously unrecognized temperate interval in the British Quaternary record

ABSTRACTAlthough fossil assemblages from the late Early Pleistocene are very rare in Britain, the site of Westbury Cave in Somerset, England, has the potential to address this gap. The mammal fossils recovered previously from the Siliceous Member in Westbury Cave, though few in number, have hinted at an age for the deposits that is as yet unparalleled in Britain. Here, we describe the first bona fide occurrence of Hippopotamus in the British Early Pleistocene, discovered during recent reinvestigation of the Siliceous Member. The hippo fossil indicates a refined biochronological age of ca. 1.5–1.07 Ma for the Siliceous Member and a palaeoclimate that was warm and humid, which accords well with previous palaeoenvironmental inferences. A synthesis of late Early Pleistocene hippo occurrences suggests that the Siliceous Member hippo may have been part of an early colonization of north‐west Europe by these megaherbivores, possibly during MIS (Marine Oxygen Isotope Stage) 31. Alternatively, it evidences a currently cryptic northward migration during an even earlier temperate phase. In either case, the Siliceous Member is likely to represent a warm period that has not been recognized previously in the British Quaternary record.

High Intrapatient Variability in Tacrolimus Exposure Calculated Over a Long Period Is Associated With De Novo Donor-Specific Antibody Development and/or Late Rejection in Thai Kidney Transplant Patients Receiving Concomitant CYP3A4/5 Inhibitors.

High intrapatient variability in tacrolimus trough levels (Tac IPV) is associated with poor allograft outcomes. Tac IPV was previously calculated using trough levels 6-12 months after kidney transplantation (KT). Data on the accuracy of Tac IPV calculation over a longer period, the association between high Tac IPV and donor-specific antibody (DSA) development after KT in Asian patients, and the role of IPV in patients receiving concomitant cytochrome P450 (CYP)3A4/5 inhibitors (CYPinh) are limited. A retrospective review of patients who underwent KT at our center in 2005-2015, and who received Tac with mycophenolate during the first 2 years after KT was performed. IPV was calculated using Tac levels adjusted by dosage. DSA was monitored annually after KT using a Luminex microbead assay. In total, 236 patients were enrolled. CYPinh were prescribed to 189 patients (80.1%): 145 (61.4%), 31 (13.1%), and 13 (5.5%) received diltiazem, fluconazole, and ketoconazole, respectively. Mean IPV calculated from adjusted Tac levels for 6-12 months (IPV6-12) and 6-24 months (IPV6-24) after KT were 20.64% ± 11.68% and 23.53% ± 10.39%, respectively. Twenty-six patients (11%) showed late rejection and/or DSA occurrence, and had significantly higher IPV6-24 (29.42% ± 13.78%) than others (22.77% ± 9.64%; P = 0.02). There was no difference in IPV6-12 (24.31% ± 14.98% versus 20.17% ± 10.90%; P = 0.18). IPV6-12 and IPV6-24 were comparable in patients who did and did not receive CYPinh. When using mean IPV6-24 as a cutoff, patients with higher IPV6-24 had a higher probability of developing DSA and/or late rejection (P = 0.048). Tac IPV6-24 was higher and more significantly associated with DSA development and/or late rejection than Tac IPV6-12, independent of Tac trough level. This is the first study to demonstrate the impact of high IPV on DSA development in Asian patients, and that Tac IPV is comparable between patients with and without CYPinh.

Intrauterine Intussusception Presenting as Fetal Ascites and Meconium Peritonitis

Intussusception is a well-known cause of intestinal obstruction in children. Its occurrence in fetus as an intrauterine incidence is extremely rare and poses a diagnostic difficulty. Intrauterine intussusception may result in intestinal atresia once the gangrenous segment resorbed. However, a very late occurrence of intussusception just prior to delivery may present as meconium peritonitis. We are reporting a case of premature baby who was born at 35 weeks gestation via emergency caesarean for breech in labour. Routine scan 4 days prior to the delivery showed evidence of fetal ascites. She was born with good Apgar Score and weighed 2.5kg. Subsequently she developed respiratory distress syndrome requiring mechanical ventilation. She passed minimal meconium once after birth then developed progressive abdominal distension and vomiting. Abdominal radiograph on day 4 of life revealed gross pneumoperitoneum and bedside percutaneous drain was inserted to ease the ventilation. Upon exploratory laparotomy, a single ileal perforation was seen 20cm from ileocecal junction with an intussusceptum was seen in the distal bowel. Gross meconium contamination and bowel edema did not favour the option of primary anastomosis, thus stoma was created. Reversal of stoma was performed a month later and she recovered well. Fetus with a complicated intrauterine intussusception may present with fetal ascites and their postnatal clinical and radiological findings need to be carefully assessed for evidence of meconium peritonitis; in which a timely surgical intervention is required to prevent the sequelae of prolonged intraabdominal sepsis in this premature baby.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S18

Cutaneous Metastasis from Colorectal Cancer: Making Light on an Unusual and Misdiagnosed Event.

Cutaneous metastasis from solid tumors is a rare event and usually represents a late occurrence in the natural history of an advanced visceral malignancy. Rarely, cutaneous metastasis has been described in colorectal cancer patients. The most frequent cutaneous site of colorectal metastasis is the surgical scar in the abdomen following the removal of the primary malignancy, followed by the extremities, perineum, head, neck, and penis. Metastases to the thigh and back of the trunk are anecdotical. Dermatological diagnosis of cutaneous metastasis can be quite complex, especially in unusual sites, such as in the facial skin or thorax and in cases of single cutaneous lesions since metastasis from colorectal cancer is not usually the first clinical hypothesis, leading to misdiagnosis. To date, due to the rarity of cutaneous metastasis from colorectal cancer, little evidence, most of which is based on case reports and very small case series, is currently available. Therefore, a better understanding of the clinic-pathological characteristics of this unusual metastatic site represents an unmet clinical need. We present a large series of 29 cutaneous metastases from colorectal cancer with particular concerns regarding anatomic localization and the time of onset with respect to primitive colorectal cancer and visceral metastases.

Late Sandbian (Sa2) radiolarians of the Pingliang Formation from the Guanzhuang section, Gansu Province, China

AbstractA diverse, well-preserved radiolarian assemblage is reported from the Sandbian age Climacograptus bicornis Graptolite Biozone. This new assemblage, recovered from the Pingliang Formation in the Guanzhuang section, China, includes six new species along with 13 other previously described taxa. Geminusphaera new genus incorporates G. grandis n. sp. and G. kongtongensis n. sp. and is proposed for inaniguttids constructed from two distinct porous spheres bearing seven or more primary spines. Protopylentonema new genus is introduced to incorporate pylomate entactinarians with five-rayed initial spicules. It includes P. ordosensis n. sp. as well as P. aperta, P. rimata, and P. insueta that were formerly assigned to Kalimnasphaera. Micro-computed tomography investigation of skeletal microstructure supports establishment of the new genera together with other new spumellarian species: Haplotaeniatum implexa n. sp., Inanigutta quadrispinosa n. sp., and Kalimnasphaera pingliangensis n. sp. It also indicates that family-level reassignment of Etymalbaillella from the Proventocitidae to the Ceratoikiscidae is appropriate.Global distribution of Late Ordovician radiolarian occurrences highlights a strong preference for areas with equatorial to tropical sea surface temperatures. This must have led to ecological stress among radiolarian communities in adapting to global cooling in the Hirnantian.UUID: http://zoobank.org/3d3f55b8-0e70-4f9f-9738-265750d8ec3a.

Carbonate precipitation, U-series dating and Uisotopic variations in a Holocene travertine platform at Bad Langensalza - Thuringia Basin, Germany

A fossil remain of porcupine, a large-sized rodent hitherto unknown in Portugal, was identified during the 2010-13 excavation of the Last Interglacial deposit of Figueira Brava cave. The specimen is a left hemimandible retaining the PM/4 to M/2 series but lacking the incisor and the M/3. Based on the analysis of its morphological and odontometric features, we assign the fossil to Hystrix cristata (Linnaeus, 1758). Nowadays, H. cristata is found in Africa as well as, recently introduced, in Italy. Most Late Pleistocene occurrences of the genus are assigned to the species Hystrix (Acanthion) vinogradovi but, as demonstrated by the fossil discovered in Figueira Brava, H. cristata once existed in Europe.

Late Post-Operative Occurrence of Dentin Hypersensitivity in Adult Patients Following Allogeneic Hematopoietic Stem Cell Transplantation-A Preliminary Report.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is one of the most commonly performed transplantation procedures nowadays. Despite the significant progress made in the treatment, alloHSCT is still associated with numerous complications also affecting the oral cavity. One of them is dentin hypersensitivity (DH)—a sharp, short-term pain that occurs when stimuli act on exposed dentin. Various authors point out that DH may result in a significantly lower quality of life, among other things by impeding the consumption of food as well as causing difficulties in daily oral hygiene. The aim of the study was a preliminary analysis of the incidence rate and severity of DH pain in adult patients during late period after alloHSCT. The impact of chronic graft-versus-host disease (cGvHD) and time after alloHCT were also considered. A total of 80 patients were examined. cGvHD was identified in 52 participants. The incidence rate and severity of DH pain was assessed on the basis of a questionnaire and a clinical examination. DH pain appeared a serious problem in late period after alloHSCT regardless of post-transplant time. DH primarily affected cGvHD patients. The prevention-treatment protocol for DH should be developed for this group.

HirnantiaFauna from the Condroz Inlier, Belgium: another case of a relict Ordovician shelly fauna in the Silurian?

AbstractThe end-Ordovician mass extinction, linked to a major glaciation, led to deep changes in Hirnantian–Rhuddanian biotas. TheHirnantiaFauna, the first of two Hirnantian survival brachiopod-dominated communities, characterizes the lower–mid Hirnantian deposits globally, and its distribution is essential to understand how the extinction took place. In this paper, we describe, illustrate, and discuss the first macrofossiliferousHirnantiaFauna assemblage from Belgium, occurring in the Tihange Member of the Fosses Formation at Tihange (Huy), within the Central Condroz Inlier. Six fossiliferous beds have yielded a low-diversity, brachiopod-dominated association. In addition to the brachiopods (Eostropheodonta hirnantensis,Plectothyrella crassicosta,Hirnantiasp., andTrucizetina? sp.), one trilobite (Mucronaspissp.), four pelmatozoans (Xenocrinussp.,Cyclocharax[col.]paucicrenulatus,Conspectocrinus[col.]celticus, andPentagonocyclicus[col.] sp.), three graptolites (Cystograptus ancestralis,Normalograptus normalis, and ?Metabolograptussp.), together with indeterminate machaeridians and bryozoans were identified. The graptolite assemblage, from theAkidograptus ascensus-Parakidograptus acuminatusBiozone, indicates an early Rhuddanian (Silurian) age, and thus, an unexpectedly late occurrence of a typicalHirnantiaFauna. This Belgian association may represent an additional example of relictHirnantiaFauna in the Silurian, sharing characteristics with the only other known from Rhuddanian rocks at Yewdale Beck (Lake District, England), although reworking has not been completely ruled out. The survival of these Hirnantian taxa into the Silurian might be linked to delayed post-glacial effects of rising temperature and sea-level, which may have favored the establishment of refugia in these two particular regions that were paleogeographically close during the Late Ordovician–early Silurian.

New early Campanian characiform fishes (Otophysi: Characiformes) from West Texas support a South American origin for known Late Cretaceous characiforms from North America

Fossil characiform dentaries from the “Lowerverse locality” in the lower Campanian portion of the Aguja Formation of West Texas represent a rare Late Cretaceous occurrence of characiform fishes in North America. Two morphotypes are represented. Both of them exhibit ventrally encased, mandibular laterosensory canals and distinctive anterior lobes unique to the characiform symphyseal ‘hinge’. The first, dentigerous morphotype closely resembles fossil characiform dentaries from the Campanian Dinosaur Park Formation of Alberta, Canada. All of these are collectively referred herein to Primuluchara laramidensis gen et sp. nov. The second morph is edentulous as in extant curimatids and pertains to a different new species herein referred to Eotexachara malateres gen et sp. nov. Numerous Weberian vertebral centra recovered at Lowerverse suggest that characiforms were abundant in the coastal, subaquatic paleoenvironment here. The early Campanian age of the Aguja Formation characiforms supports previous temporal estimates regarding the arrival of characiforms in North America from either Europe or South America as inferred from previous molecular and/or paleontological studies. The presence of morphologically related, but geotemporally divergent species in Campanian strata of West Texas and Alberta indicates a south-to-north radiation among Laramidian characiforms and points to a southerly origin for ancestral forms. Santonian – Maastrichtian occurrences of characiforms in Europe suggests that they reached the limit of their dispersal there and were unable to invade southern Laramidia by the early Campanian. Whether the likely dispersal of characiforms from South America occurred via an archaeo- or telolimnitic progression remains unclear. However, it is plausible that euryhalinity played some role in their coastal dispersal.

De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017.

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi’s sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients’ age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

Effects of precipitate origin and precipitate-free zone development on the tensile creep behaviors of a hot-rolled Mg-13wt%Gd binary alloy

In heat-resistant Mg Gd based alloys, the relationship between the collective effects of precipitate origin and precipitate-free zone (PFZ) development on the creep resistance is still unclear. In this work, a hot-rolled Mg-13wt%Gd binary alloy was treated by solid solution (SS sample) and peak aging (AA sample). After peak aging, static precipitated β ′ phases were widely generated and PFZs were directly formed along both sides of the grain boundaries in AA sample. Tensile creep tests were performed at 523 K on both SS and AA samples. During creep testing, dynamic precipitated β ′ phases were gradually generated in SS sample while the β ′ phases persisted as large scales in AA sample. The dominant creep mechanisms of SS sample were twinning and cross-slip composed by < a > dislocations, since the late occurrence and low density of β ′ phases failed in hindering the movement < a > dislocations at the beginning of steady creep stage. On the contrary, the large-scale β ′ phases reduced the space for dislocation movement and succeeded in retarding cross-slip, leading to pyramidal < c + a > slip being the main creep mechanism of AA sample. Besides, PFZs were formed in SS sample (from zero to ~1.1 μm) while they became narrower in AA sample (from ~5 μm to ~1.7 μm). The large decreased ratio of PFZ width, the large scale of static precipitated β ′ phases and the resultant pyramidal < c + a > slip effectively enhanced the creep resistance of AA sample. Accordingly, AA sample behaved a higher creep resistance in comparison to SS sample at 523 K. It is hoped that the roles of precipitate origin and PFZ development in the creep properties can enrich the theories and methods in improving the service performance of Mg Gd series at medium to high temperatures. • Wide PFZs and large-scale static precipitates are obtained after peak aging. • For peak-aged alloy, PFZs are narrowed during creep and creep resistance rises. • For solid solute alloy, PFZs are widely developed and creep resistance falls. • Static precipitates can retard a -cross slip whereas dynamic precipitates fail. • As a -cross slip is delayed, pyramidal slip is activated to enhance creep resistance.

Sequential Lymphoma between Classical Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma: Clinicopathological Characteristics and Outcome of 18 Patients from Lysa Center

Sequential Lymphoma between Classical Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma: Clinicopathological Characteristics and Outcome of 18 Patients from Lysa Center

Role of Erythropoietin in the Late Anemia of Patients with Chronic Myeloid Leukemia Treated Frontline with Imatinib

Background Late occurrence of moderate/severe anemia in patients with Chronic Myeloid Leukemia (CML) during long-lasting treatment with imatinib has been reported in a sizeable rate and seems to be more common in elderly patients. Treatment of such complication is subjective and the possible role of erythropoietin (EPO) still unclear.Methods To highlight this issue, we revised retrospectively 37 CML patients treated at 10 Institutions in Italy with frontline imatinib for at least 24 months and in stable complete cytogenetic response (CCyR) who developed a late chronic anemia and were treated with EPO. Late chronic anemia was defined as the presence of persistent (> 3 months) and otherwise unexplained (creatinine level < 2 mg/dl, normal iron balance, bilirubin level < 2 mg/dl, folate and Vitamin B12 in the normal range) Hb levels < 11 g/dl which occurred > 6 months from imatinib start. The main clinical features of the patients at diagnosis were as follows: male/female 21/16 (56.8%/43.2%), median age 69.4 years [interquartile range (IQR) 62.7 - 74.8], median Hb 12.2 g/dl (IQR 10.9 - 13.5), median WBC 50.3 x 109/l (IQR 28.7 - 87.2), median PLTS 384 x 109/l (IQR 277 - 645). According to Sokal risk classification, available in 35 patients, 7 (20.0%) were low risk, 24 (68.6%) intermediate risk and 4 (11.4%) high risk.Results Median time from imatinib start to EPO treatment was 44.2 months (IQR 21.6 - 100.2). At baseline of EPO treatment, all patients were in stable CCyR and 31/37 (83.7%) were also in stable MR 3.0. Median Hb value at baseline was 9.9 g/dl (IQR 9.2 - 10.2): four out 37 patients (10.8%) needed packed red cell transfusions before the starting of EPO treatment. Endogenous EPO level at baseline was available in 22 patients, with a median value of 21.5 mU/ml (IQR 13.6 - 35.7). Alpha-EPO (40,000 UI weekly) was employed in 31 cases, beta-EPO (30,000 UI weekly) in 4 cases and darbopoietin (150 mcg/weekly) in 2 patients. On the whole, 29 patients (78.3%) achieved an erythroid response, defined as a stable (> 3 months) increment > 1.5 g/dl of Hb levels, and 8 patients (21.7%) were resistant to treatment: median HB values at different time-points during EPO treatment are reported in the figure 1. Among responding patients, 3 had a relapse of anemia after 8, 24 and 96 months from EPO start, respectively, and stopped EPO, 4 died while in response from CML unrelated causes, 2 stopped EPO while in response: the remaining 20 responding patients are still alive in response and still in treatment with EPO. No EPO-related toxicity was observed. 5-year overall survival from EPO treatment of the entire cohort was 81.0% (95%CI 65.7 - 96.3).Conclusions Results with EPO in the treatment of late chronic anemia which occurs during long-lasting imatinib treatment are encouraging, with a high rate of response and an excellent safety profile: however, larger prospective studies are warranted to define more precisely the role (when to start EPO?, at what dosage?, for how long?) of such an approach in the treatment of this common late complication of prolonged imatinib therapy. [Display omitted] DisclosuresBocchia:Celgene: Other: Travel grant; Novartis: Other: Travel grant; Roche: Other: Travel grant; Jansen: Other: Travel grant. Galimberti:Novartis: Speakers Bureau; Pfizer: Speakers Bureau; Bristol-Myers Squibb: Speakers Bureau; Incyte: Speakers Bureau. Breccia:Incyte: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Bristol Myers Squibb: Consultancy. Pane:Novartis: Honoraria, Speakers Bureau.

Dating the Great Divergence

AbstractNew data on Dutch and British GDP/capita show that at no time prior to 1750, perhaps not before 1800, did the leading countries of northwestern Europe enjoy sustained strong growth in GDP/capita. Such growth in income per head as did occur was highly episodic, concentrated in a few decades and then followed by long periods of stagnation of income per head. Moreover, at no time before 1800 did the leading economies of northwestern Europe reach levels of income per capita much different from peak levels achieved hundreds of years earlier in the most developed regions of Italy and China. When the Industrial Revolution began in Britain, it was not preceded by patterns of pre-modern income growth that were in any way remarkable, neither by sustained prior growth in real incomes nor exceptional levels of income per head. The Great Divergence, seen as the onset of sustained increases in income per head despite strong population growth, and achievement of incomes beyond pre-modern peaks, was a late occurrence, arising only from 1800.

Gene Expression Changes in a Model Neuron Cell Line Exposed to Autoantibodies from Patients with Traumatic Brain Injury and/or Type 2 Diabetes

Traumatic brain injury and adult type 2 diabetes mellitus are each associated with the late occurrence of accelerated cognitive decline and Parkinson’s disease through unknown mechanisms. Previously, we reported increased circulating agonist autoantibodies targeting the 5-hydroxytryptamine 2A receptor in plasma from subsets of Parkinson’s disease, dementia, and diabetic patients suffering with microvascular complications. Here, we use a model neuron, mouse neuroblastoma (N2A) cell line, to test messenger RNA expression changes following brief exposure to traumatic brain injury and/or type 2 diabetes mellitus plasma harboring agonist 5-hydroxytryptamine 2A receptor autoantibodies. We now report involvement of the mitochondrial dysfunction pathway and Parkinson’s disease pathways in autoantibody-induced gene expression changes occurring in neuroblastoma cells. Functional gene categories upregulated significantly included cell death, cytoskeleton-microtubule function, actin polymerization or depolymerization, regulation of cell oxidative stress, mitochondrial function, immune function, protein metabolism, and vesicle function. Gene categories significantly downregulated included microtubule function, cell adhesion, neurotransmitter release, dopamine metabolism synaptic plasticity, maintenance of neuronal differentiation, mitochondrial function, and cell signaling. Taken together, these results suggest that agonist 5-hydroxytryptamine receptor autoantibodies (which increase in Parkinson’s disease and other forms of neurodegeneration) mediate a coordinating program of gene expression changes in a model neuron which predispose to neuro-apoptosis and are linked to human neurodegenerative diseases pathways.

Hans Joachim Scherer: an under-recognized pioneer of glioma research in Belgium

Hans Joachim Scherer (1906-1946) was a German pathologist who fled Germany to Belgium to work on glioma genesis, growth and progression. Despite being seldom cited, and due to the contributions discussed in this article, Hans Joachim Scherer, can be considered a founding father of contemporary neuropathology and glioma research. We discuss Scherer's achievements in glioma classification, glomerular structures of glioma, primary and secondary glioblastoma, glioma growth patterns, non-resectability of glioma, pseudopalisadic necrosis and the late occurrence of symptoms in glioma.