Initial pulse of Siberian Traps sills as the trigger of the end-Permian mass extinction.

Mass extinction events are short-lived and characterized by catastrophic biosphere collapse and subsequent reorganization. Their abrupt nature necessitates a similarly short-lived trigger, and large igneous province magmatism is often implicated. However, large igneous provinces are long-lived compared to mass extinctions. Therefore, if large igneous provinces are an effective trigger, a subinterval of magmatism must be responsible for driving deleterious environmental effects. The onset of Earth's most severe extinction, the end-Permian, coincided with an abrupt change in the emplacement style of the contemporaneous Siberian Traps large igneous province, from dominantly flood lavas to sill intrusions. Here we identify the initial emplacement pulse of laterally extensive sills as the critical deadly interval. Heat from these sills exposed untapped volatile-fertile sediments to contact metamorphism, likely liberating the massive greenhouse gas volumes needed to drive extinction. These observations suggest that large igneous provinces characterized by sill complexes are more likely to trigger catastrophic global environmental change than their flood basalt- and/or dike-dominated counterparts.Although the mass end-Permian extinction is linked to large igneous provinces, its trigger remains unclear. Here, the authors propose that the abrupt change from flood lavas to sills resulted in the heating of sediments and led to the release of large-scale greenhouse gases to drive the end-Permian extinction.

Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma.

High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30% and 48% respectively. High CD3+ cell dose (>3 × 108/kg) infusion was associated with more acute GvHD (grade 2-4) (47% vs 17.5%; P=0.03), extensive chronic GvHD (80% vs 50%; P=0.04), increased transplant-related mortality (26.3% vs 5%; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (

Anatomy of the long head of biceps femoris: An ultrasound study.

Hamstring strains, particularly involving the long head of biceps femoris (BFlh) at the proximal musculotendinous junction (MTJ), are commonly experienced by athletes. With the use of diagnostic ultrasound increasing, an in-depth knowledge of normal ultrasonographic anatomy is fundamental to better understanding hamstring strain. The aim of this study was to describe the architecture of BFlh, using ultrasonography, in young men and cadaver specimens. BFlh morphology was examined in 19 healthy male participants (mean age 21.6 years) using ultrasound. Muscle, tendon and MTJ lengths were recorded and architectural parameters assessed at four standardised points along the muscle. Measurement accuracy was validated by ultrasound and dissection of BFlh in six male cadaver lower limbs (mean age 76 years). Intra-rater reliability of architectural parameters was examined for repeat scans, image analysis and dissection measurements. Distally the BFlh muscle had significantly (P < 0.05) shorter fascicles and larger pennation angles than proximal sites. Agreement between ultrasound and dissection (cadaver study) was excellent for all architectural parameters, except pennation angle (PA), and MTJ length. All other measures demonstrated good-excellent repeatability. BFlh is not uniform in architecture when imaged using ultrasound. It is likely that its distal-most segment is better suited for force production in comparison to the more proximal segments, which show excursive potential, traits which possibly contribute to the high rate of injury at the proximal MTJ. The data presented in this study provide specific knowledge of the normal ultrasonographic anatomy of BFlh, which should be of assistance in analysing BFlh injury via imaging. Clin. Anat. 29:738-745, 2016. © 2016 Wiley Periodicals, Inc.

Adolph Barkan (1845-1935), European ophthalmologist in San Francisco.

Adolph Barkan, a mid-19th century Central European-born and -trained ophthalmologist, spent almost half his nearly 91 years in a very successful career on the West Coast of the United States. His activities included intimate involvement in the development of a private medical school and with this school's acquisition by Stanford University as its medical school. In retirement, he founded, financed, and stocked a large medical history library at that university. In the 1890s, Siegfried Czapski, the developer of the Carl Zeiss corneal biomicroscope, the direct precursor of today's slitlamp, incorporated Barkan's suggestion that Czapski replace the planned monoscopic binocular microscope with a stereoscopic binocular one, an essential modification of the device. This Zeiss invention lacked only the slit illumination of today's instrument. Comments he wrote in a memoir-diary during World War I explain how he came to the decision to stray and to stay so far from his roots.

The effect of upper limb position on ultrasonographic arterial flow to the ulnar nerve.

We measured the pulsatility indices in the inferior collateral and posterior recurrent ulnar arteries, which supply the ulnar nerve at the elbow, in 38 conscious adults. Compared with a straight 30° abducted arm, elbow flexion to 120° reduced the mean (SD) pulsatility index in the inferior artery and increased the pulsatility index in the posterior artery: from 3.36 (0.86) to 3.04 (0.94), p = 0.001, and from 3.14 (0.81) to 3.64 (1.05), p < 0.0005, respectively. The mean (95% CI) pulsatility index in the inferior artery was unaffected by shoulder abduction to 120°, but it was decreased in the posterior artery in men, from 3.06 (2.76-3.36) to 2.64 (2.34-2.95), but not women, from 3.22 (2.94-3.50) to 3.25 (2.97-3.53), p = 0.01 for men vs women. Researchers should measure arterial pulsatility indices under general anaesthesia and associate them with measures of nerve function.

Wilhelm August Gottlieb Manniske, MD (1769-1835): microscope use during removal of buried corneal body in 1792.

In 1792, a priest in Germany consulted a young doctor about a buried corneal foreign body hidden in a small, hard mass that partly covered the pupil. During removal of the foreign body, the doctor inspected the corneal incision with a microscope to confirm the suspected presence of the foreign body. This may be the first use of a microscope in eye surgery.

Long-term follow-up of a pilot study using a chemotherapy-alone protocol for killer Ig-like receptor-ligand-mismatched haploidentical haematopoietic SCT.

Advanced haematological malignancies are incurable without allogeneic haematopoietic SCT (HSCT). Many patients do not have a human leukocyte Ag (HLA)-matched donor; hence, haploidentical HSCT has been explored for some 20 years. Previous poor outcomes have improved recently with modifications, including the use of killer Ig-like receptor (KIR)-ligand-mismatched donors and highly T-cell-depleted megadose CD34+ stem cell infusions. Haploidentical HSCT was undertaken in 10 patients with heavily pretreated and advanced myeloid malignancies. Patient/donor pairs were KIR-ligand mismatched (GVL direction). Conditioning regimen was ATG, melphalan, fludarabine and thiotepa. G-CSF-mobilized PBSCs were CD34+ cell selected. No post transplant immunosuppression was given. Two patients died early; all others had sustained engraftment. Natural killer cell recovery, often to supranormal levels, occurred early, whereas CD4+ T-cell recovery was delayed. Acute GVHD occurred in three of eight (30%) patients, and chronic GVHD occurred in three of six (50%) evaluable patients. No infections with Candida or Aspergillus developed in seven patients receiving caspofungin prophylaxis. Three of 10 (30%) patients were alive and disease free at 10.1, 6 and 5.4 years post transplant (Karnovsky scores of 100%). In this heavily pretreated cohort with very advanced myeloid malignancies, KIR-ligand-mismatched haploidentical HSCT cured a significant proportion of patients.

Reduced-intensity conditioned allogeneic haematopoietic stem cell transplantation results in durable disease-free and overall survival in patients with poor prognosis myeloid and lymphoid malignancies: eighty-month follow-up.

The long-term outcome of patients with haematological malignancies treated with reduced-intensity conditioned allogeneic peripheral blood stem cell transplantation is not known. We report the outcome of 79 patients with poor-risk myeloid and lymphoid malignancies transplanted with reduced-intensity conditioning (RIC) regimens. The diagnoses include AML/myelodysplastic syndrome (n=43), non Hodgkin's lymphoma (n=30), Hodgkin's lymphoma (n=3), ALL (n=2) and CML (n=1). For the entire cohort, the disease-free survival (DFS) and OS were 61.2 and 35.7%, respectively. Twenty patients relapsed, 18 within the first three years, and 14 patients succumbed to progressive disease. Overall, 31 patients died from transplant-related complications within the first three years. Day 100 non-relapse mortality correlated with a higher total nucleated cell dose in the graft (odds ratio: 3.9). For those in CR at 3 years, the DFS and OS were 84.2 and 81.1%, respectively. Furthermore, of 43 patients with active disease at the time of transplantation, 16 remained in CR after 3 years. The majority of the long-term survivors were functioning independently. One patient died from a second malignancy. No post-transplant lymphoproliferative disorder was seen. In conclusion, durable disease control was achieved after RIC allogeneic stem cell transplantation for patients with advanced myeloid and lymphoid malignancies.

Intermediate-dose CY and G-CSF more efficiently mobilize adequate numbers of PBSC for tandem autologous PBSC transplantation compared with low-dose CY in patients with multiple myeloma.

BACKGROUND: Autologous PBSC transplantation is the standard care for patients with multiple myeloma. The most common regimen used to mobilize PBSC consists of CY and G-CSF. METHODS: We retrospectively analyzed the efficacy and toxicity of two regimens of CY for PBSC mobilization: low-dose CY (1-2 g/m(2), LD-CY, n=61) plus G-CSF, and intermediate-dose CY (3-4 g/m(2), ID-CY, n=26) plus G-CSF. RESULTS: In the LD-CY group, 5.17 (0.23-17.3)x10(6) CD34(+) cells/kg, and in the ID-CY group 7.71 (0.08-26.4)x10(6) CD34(+) cells/kg (P=0.018), were collected. Although >/=2x10(6)/kg CD34(+) cells were collected in 89% of the LD-CY group and 92% of the ID-CY group, this was achieved after a single leukapheresis in 54% of the LD-CY group and 92% of the ID-CY group (P=0.0001). Patients who are to have tandem autologous PBSC transplants require >/=4x10(6)/kg CD34(+) cells. This was achieved in only 65% patients in the LD-CY group but 88% in the ID-CY group (P=0.05). Among patients who had not had prior melphalan and/or >12 months of prior treatment, 74% in the LD-CY group and 100% in ID-CY group mobilized >/=4x10(6)/kg CD34(+) cells. Febrile neutropenia was more frequent in the ID-CY group (38% vs. 13%). DISCUSSION: In conclusion, compared with LD-CY, patients receiving ID-CY were more likely to collect a total CD34(+) cell number adequate for tandem autologous PBSC transplantation. The increased toxicity was manageable and considered acceptable.

Kappa immunoglobulin light chain polymorphisms and survival after allogeneic transplantation for B-cell malignancies: a potential graft-vs-leukaemia target.

In the human leucocyte antigen (HLA)-matched haematopoietic stem cell transplantation (HSCT) setting, minor histocompatibility antigen (mHA) disparities between recipient and donor can lead to graft-vs-host disease (GVHD) or graft rejection. Graft-vs-leukaemia (GVL) effect is a beneficial T-cell-mediated immune response that can also occur following HLA-matched HSCT. mHAs with tissue expression restricted to cells of the haematopoietic system are particularly relevant as immunotherapeutic targets for destroying malignant cells without inducing GVHD. Therefore, it is important to identify further haematopoietic-restricted polymorphic mHAs, which may have the potential to be used clinically for adoptive immunotherapy. Polymorphic mismatching of minor antigens, such as the B-cell-specific protein, the kappa immunoglobulin light chain (kappa) may play a role in the incidence of GVL and therefore the survival of transplant recipients following transplantation for B-cell malignancies. Polymorphisms in the constant region of the immunoglobulin kappa polypeptide chain have been defined involving single amino acid changes at positions 153 and 191. In this study, 51 HLA-matched B-cell malignancy transplant pairs were kappa typed by polymerase chain reaction and restriction enzyme digestion to investigate the association between kappa allotype disparity and outcome after transplantation. Kappa allotype disparity between transplant pairs may be associated with an increased survival compared with pairs not mismatched for kappa, as kappa mismatched recipients had a higher percentage of complete remissions and a decreased level of relapse in comparison with the nonmismatched recipients. HLA peptide prediction software was used to determine which HLA types were the best binders for kappa peptides. It was observed that patients with tissue types predicted to bind the kappa Km(1,2) peptides had better survival outcomes and no relapse compared with those with tissue types not predicted to bind the kappa Km(1,2) peptides. This study may contribute to the assessment of the clinical role of kappa with regard to the outcome of allogeneic transplantation for B-cell malignancies.

Successful mobilization of peripheral blood stem cells using recombinant human stem cell factor in heavily pretreated patients who have failed a previous attempt with a granulocyte colony-stimulating factor-based regimen.

To assess the efficacy of recombinant human stem cell factor (rHuSCF), 48 patients who had failed to mobilize >2.0 x 10(6) CD34+ cells/kg with granulocyte colony-stimulating factor (G-CSF) (10 microg/kg twice daily) with, or without, concomitant chemotherapy (G-CSF-based regimen), were remobilized with the addition of rHuSCF (20 microg/kg/day). In all, 18/48 (38%) achieved a total of >2.0 x 10(6) CD34+ cells/kg with the second rHuSCF-based mobilisation alone and 29/48 (60%) achieved a cumulative total of >2.0 x 10(6) CD34+ cells/kg following remobilization. Inclusion of chemotherapy in the mobilization regimen resulted in a higher yield of CD34+ cells/kg for both the initial G-CSF-based and subsequent rHuSCF-based regimens (0.90 vs 0.54, P < 0.01 and 2.36 vs 1.34, P < 0.01, respectively). The total peripheral blood stem cells PBSC collected from the G-CSF-based regimen, performance status, baseline platelet count and albumin were significantly associated with successful remobilization. Patients with multiple myeloma were also more likely to successfully remobilize. There was no threshold of total collected from the failed G-CSF-based regimen below which successful remobilization with the rHuSCF-based regimen was not possible. We therefore propose a predictive model [PBSC expected = 0.6+(G-CSF-based total collection)+2 (rHuSCF-based day 1 collection)] to calculate the cumulative total of PBSC expected following a maximum of five leukaphereses. This algorithm may permit the early identification of patients who are unlikely to achieve sufficient PBSC for transplantation and allow physicians to direct the resources involved in PBSC collection in a more appropriate and economical manner.

Color vision deficits during laser lithotripsy using safety goggles for coumarin green or alexandrite but not with holmium:YAG laser safety goggles.

PURPOSE: Laser lithotripsy requires urologists to wear laser eye protection. Laser eye protection devices screen out specific light wavelengths and may distort color perception. This study tests whether urologists risk color confusion when wearing laser eye protection devices for laser lithotripsy. MATERIALS AND METHODS: Urologists were tested with the Farnsworth Dichotomous Test for Color Blindness (D-15) and the Farnsworth-Munsell 100-Hue Test (FM-100) without (control) and with laser eye protection devices for coumarin green, alexandrite and holmium:YAG lasers. Error scores were tabulated. The pattern of color deficits was characterized with confusion angles, confusion index (C-index), scatter index (S-index) and color axes. Laser eye protection devices were tested with spectrophotometry for spectral transmittance and optical density. RESULTS: The D-15 transposition errors (mean plus or minus standard deviation) for control, holmium:YAG, alexandrite and coumarin green laser eye protection were 0 +/- 0, 0 +/- 0, 0.3 +/- 0.5 and 6.4 +/- 1.6, respectively (p = 0.0000001). The FM-100 error scores (mean plus or minus standard deviation) were 20 +/- 15, 20 +/- 14, 91 +/- 32 and 319 +/- 69, respectively (p = 0.0001). The confusion index scores indicated a mild color confusion for the alexandrite and pronounced color confusion for the coumarin green laser eye protection. The confusion angles and scatter indexes mimicked a congenital blue-yellow deficit for coumarin green laser eye protection. Color axes showed no significant deficits for control or holmium:YAG laser eye protection in any subject, red-green axis deficits in 3 of 6 tested with alexandrite and blue-yellow axis deficits in 12 of 12 tested with coumarin green (p < 0.001). Spectrophotometry showed that laser eye protection for coumarin green blocks light less than 550 nm., alexandrite blocks light greater than 650 nm. and holmium:YAG blocks light greater than 825 nm. CONCLUSIONS: Laser eye protection for coumarin green causes pronounced blue-yellow color confusion, whereas alexandrite causes mild red-green color confusion among urologists, holmium:YAG causes no significant color confusion compared to controls. The differences are explained by laser eye protection spectrophotometry characteristics and visual physiology.

Scratching the surface: mental health training for rural health workers.

This paper will describe the Mental Health Training for Rural Health Workers Project that was completed in 1995 under the Rural Health Support Education and Training Program. The lack of specialist mental health services in rural areas means that generalist health workers need to provide mental health services in rural communities. Generalist health workers often feel ill-equipped to help people who require mental health services. The aim of this project was to provide generalist workers in rural areas with practical skills and knowledge in order to help people with mental health disorders and promote positive mental health. The project involved an initial needs survey, the development of education and training material, the implementation of the training, and evaluation of the project.

Positive expectations predict health after heart transplantation.

We explored the relations between positive expectations and adjustment, adherence, and health in cardiac transplant patients. Thirty-one patients and their nurse completed questionnaires before transplantation and at 3 times after surgery. As predicted, patients' self-reported positive expectations were generally associated with good mood, adjustment to the illness, and quality of life, even in patients who experienced health setbacks. High preoperative expectations predicted later adherence to a complex medical regimen. Positive expectations measured before the transplant predicted a substantial amount of the variance in the nurse's ratings of physical health 6 months after surgery, covarying for adherence behavior and preoperative health.

Microleakage of composite restorations with Syntac Bond and Denthesive.

The purpose of this study was to assess, in vitro, the microleakage of Class V restorations using two new dentin bonding agents with light polymerized resin composite. Restorations were placed in cavities prepared in extracted human premolars using either a bulk or incremental packing technique. Dentin bonding agents were applied according to the manufacturer's instructions. The enamel margin of each tooth was etched with 37% orthophosphoric acid. The teeth were stored for 6 weeks at 37 degrees C, thermocycled, and the restorations examined for leakage using methylene blue dye. The teeth were sectioned buccolingually through the restorations and the degree of microleakage assessed visually. All groups of teeth showed some degree of leakage at the gingival margin. There was a significant difference between the cavities restored by bulk packing of the resin composite and those where the resin had been applied incrementally for both materials (P < 0.05). There was no significant difference in leakage between the two dentin bonding agents (P > 0.05).

Heart transplantation in children: indications, complications, and management considerations.

Heart transplantation in children has increased in the last 5 years because of the availability of cyclosporine and improved surgical techniques. The primary indications for transplantation in children are dilated cardiomyopathy and complex congenital heart disease. The major complications affecting morbidity and mortality are infection and rejection. However, the development of accelerated coronary artery disease represents a serious complication limiting long-term survival. Successful rehabilitation and long-term survival depend on careful selection of potential recipients, application of stringent medical and psychosocial criteria, operative technique, comprehensive medical surveillance, and thorough and effective patient and family education.

Heart and heart-lung transplantation.

The fields of heart and combined heart-lung transplantation are in a constant state of evolution. As greater experience is gained in posttransplant management, more patients with end-stage heart and lung disease can be treated. Because the postoperative course and rehabilitation phase may be extremely difficult, only candidates who meet specific medical and psychosocial criteria are selected. During the waiting period, critical care nurses along with the transplant team are instrumental in stabilizing the emotional and physical condition of the transplant candidate. Postoperative complications requiring intensive therapy include decreased cardiac output, respiratory dysfunction, rejection, and infection. Graft atherosclerosis, obliterative bronchiolitis, and malignancy are long-term complications that may limit survival. Life-long immunosuppression and careful long-term medical surveillance are crucial to the health of the recipient. Although there are numerous emotional and physical challenges related to potentially life-threatening complications and other disturbances in daily living, the quality of life for most recipients has greatly improved.

Quality of life and coping in patients awaiting heart transplantation.

The psychosocial adaptation of patients awaiting heart transplantation has not been defined. Forty-one patients (36 men, 5 women; mean age, 48 years) completed standardized questionnaires before transplantation to assess quality of life, physical symptoms, marital/social adjustment, psychiatric morbidity, coping, and compliance to medical regimens. Also, data were obtained from spouses/partners and the transplantation nurse coordinator. Unlike previously reported findings with patients after transplantation, those awaiting transplantation report moderate dissatisfaction with quality of life. Patients report physical symptoms, functional disabilities, sexual dysfunction, and psychological distress. Nonetheless, reported levels of compliance with the medical regimens and of social support were high, and both patients and spouses/partners provided marital adjustment ratings on the Dyadic Adjustment Scale that were comparable to those of well-adjusted, happily married couples. High levels of coping also were recorded. Having a positive attitude and seeking social support were the most common coping strategies, whereas confrontation, acceptance, and escapism were relatively uncommon. In conclusion, patients awaiting heart transplantation, although dissatisfied with quality of life, maintain positive psychological and social adjustment.