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We present magnetization, specific heat, resistivity, and Hall effect measurements on the cubic B20 phase of MnGe and CoGe and compare to measurements of isostructural FeGe and electronic-structure calculations. In MnGe, we observe a transition to a magnetic state at Tc=275K as identified by a sharp peak in the ac magnetic susceptibility, as well as second phase transition at lower temperature that becomes apparent only at finite magnetic field. We discover two phase transitions in the specific heat at temperatures much below the Curie temperature, one of which we associate with changes to the magnetic structure. A magnetic field reduces the temperature of this transition which corresponds closely to the sharp peak observed in the ac susceptibility at fields above 5 kOe. The second of these transitions is not affected by the application of field and has no signature in the magnetic properties or our crystal-structure parameters. Transport measurements indicate that MnGe is metallic with a negative magnetoresistance similar to that seen in isostructural FeGe and MnSi. Hall effect measurements reveal a carrier concentration of about 0.5 carriers per formula unit, also similar to that found in FeGe and MnSi. CoGe is shown to be a low carrier density metal with a very small, nearly temperature-independent diamagnetic susceptibility.

Introduction: Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remain limited., Methods: We performed a single-center, prospective, cluster randomized, prehospital through in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (systolic blood pressure ≤90 mm Hg and heart rate ≥108 beats per minute or systolic blood pressure ≤70 mm Hg for patients at risk of hemorrhage). Primary outcome was feasibility. Secondary outcomes included 28-day and 24-hour mortality, multiple organ failure, nosocomial infection, 24-hour transfusion requirements, and arrival coagulation parameters., Results: Between November 2018 and October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent-to-treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p < 0.01) and a lower incidence of abnormal thromboelastographic measurements. No transfusion reactions during the prehospital or in-hospital phase of care were documented., Conclusion: Prehospital through in-hospital LTOWB resuscitation is safe and may be associated with hemostatic benefits. A large-scale clinical trial is feasible with protocol adjustment and would allow the effects of prehospital LTOWB on survival and other pertinent clinical outcomes to be appropriately characterized., Level of Evidence: Therapeutic/Care Management, Level II., (Copyright © 2022 American Association for the Surgery of Trauma.)

Importance: In-hospital administration of tranexamic acid after injury improves outcomes in patients at risk for hemorrhage. Data demonstrating the benefit and safety of the pragmatic use of tranexamic acid in the prehospital phase of care are lacking for these patients., Objective: To assess the effectiveness and safety of tranexamic acid administered before hospitalization compared with placebo in injured patients at risk for hemorrhage., Design, Setting, and Participants: This pragmatic, phase 3, multicenter, double-blind, placebo-controlled, superiority randomized clinical trial included injured patients with prehospital hypotension (systolic blood pressure ≤90 mm Hg) or tachycardia (heart rate ≥110/min) before arrival at 1 of 4 US level 1 trauma centers, within an estimated 2 hours of injury, from May 1, 2015, through October 31, 2019., Interventions: Patients received 1 g of tranexamic acid before hospitalization (447 patients) or placebo (456 patients) infused for 10 minutes in 100 mL of saline. The randomization scheme used prehospital and in-hospital phase assignments, and patients administered tranexamic acid were allocated to abbreviated, standard, and repeat bolus dosing regimens on trauma center arrival., Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality., Results: In all, 927 patients (mean [SD] age, 42 [18] years; 686 [74.0%] male) were eligible for prehospital enrollment (460 randomized to tranexamic acid intervention; 467 to placebo intervention). After exclusions, the intention-to-treat study cohort comprised 903 patients: 447 in the tranexamic acid arm and 456 in the placebo arm. Mortality at 30 days was 8.1% in patients receiving tranexamic acid compared with 9.9% in patients receiving placebo (difference, -1.8%; 95% CI, -5.6% to 1.9%; P = .17). Results of Cox proportional hazards regression analysis, accounting for site, verified that randomization to tranexamic acid was not associated with a significant reduction in 30-day mortality (hazard ratio, 0.81; 95% CI, 0.59-1.11, P = .18). Prespecified dosing regimens and post-hoc subgroup analyses found that prehospital tranexamic acid were associated with significantly lower 30-day mortality. When comparing tranexamic acid effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when tranexamic acid was administered within 1 hour of injury (4.6% vs 7.6%; difference, -3.0%; 95% CI, -5.7% to -0.3%; P < .002). Patients with severe shock (systolic blood pressure ≤70 mm Hg) who received tranexamic acid demonstrated lower 30-day mortality compared with placebo (18.5% vs 35.5%; difference, -17%; 95% CI, -25.8% to -8.1%; P < .003)., Conclusions and Relevance: In injured patients at risk for hemorrhage, tranexamic acid administered before hospitalization did not result in significantly lower 30-day mortality. The prehospital administration of tranexamic acid after injury did not result in a higher incidence of thrombotic complications or adverse events. Tranexamic acid given to injured patients at risk for hemorrhage in the prehospital setting is safe and associated with survival benefit in specific subgroups of patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02086500.

Objectives: With increased focus on early resuscitation methods following injury to improve patient outcomes, studies are employing exception from informed consent (EFIC) enrollment. Few studies have assessed patients' opinions following participation in an EFIC study, and none have been conducted within the realm of traumatic hemorrhage. We surveyed those patients and surrogates previously enrolled in the Prehospital Air Medical Plasma (PAMPer) Trial to clarify their opinions related to consent and emergency research., Methods: Telephone calls were made between January-June 2019 to all patients who were enrolled under EFIC in the PAMPer study at the Pittsburgh site (169 of the 501 total patients enrolled, May 2014-Oct 2017) and their surrogates. Questions gauging approval of EFIC enrollment were asked before discussion of PAMPer trial outcomes, after disclosure of positive outcomes, and after a hypothetical negative trial outcome was proposed., Results: Of the total 647 telephone calls made, ninety-three interviews, reflecting 70 of 169 patient enrollments, were conducted. This included 13 in which only the patient was interviewed, 23 in which the patient and a surrogate were interviewed, and 34 in which only a surrogate was interviewed. Nearly half (48.4%) of respondents did not recall their personal or family member enrollment in the study. No patients or surrogates recalled hearing about the study through community consultation or being aware of opt out procedures. Patients and surrogates were glad they were enrolled (90.3%), agreed with EFIC use for their personal enrollment (88.17%), and agreed with the general use of EFIC for the PAMPer study (81.7%). Disclosure of the true positive PAMPer study outcome resulted in a significant increase in opinions regarding personal enrollment, EFIC for personal enrollment, and EFIC for general enrollment (all p < 0.001). Disclosure of a hypothetical neutral or negative study outcome resulted in significant decreases in opinions regarding EFIC for personal enrollment (p = 0.003) and EFIC for general enrollment (p < 0.001)., Conclusions: Clinical trial participants with traumatic hemorrhagic shock enrolled with EFIC, and surrogates of such participants, are generally accepting of EFIC. The results of the trial in which EFIC was utilized significantly affected patient and surrogate agreement with personal and general EFIC enrollment.

Background: The Prehospital Air Medical Plasma (PAMPer) trial demonstrated a 30-day survival benefit among hypotensive trauma patients treated with prehospital plasma during air medical transport. We characterized resources, costs and feasibility of air medical prehospital plasma program implementation., Methods: We performed a secondary analysis using data derived from the recent PAMPer trial. Intervention patients received thawed plasma (5-day shelf life). Unused plasma units were recycled back to blood bank affiliates, when possible. Distribution method and capability of recycling varied across sites. We determined the status of plasma units deployed, utilized, wasted, and returned. We inventoried thawed plasma use and annualized costs for distribution and recovery., Results: The PAMPer trial screened 7,275 patients and 5,103 plasma units were deployed across 22 air medical bases during a 42-month period. Only 368 (7.2%) units of this total thawed plasma pool were provided to plasma randomized PAMPer patients. Of the total plasma pool, 3,716 (72.8%) units of plasma were returned to the blood bank with the potential for transfusion prior to expiration and 1,019 (20.0%) thawed plasma units were deemed wasted for this analysis. The estimated average annual cost of implementation of a thawed plasma program per air medical base at an average courier distance would be between US $24,343 and US $30,077, depending on the ability to recycle plasma and distance of courier delivery required., Conclusion: A prehospital plasma program utilizing thawed plasma is resource intensive. Plasma waste can be minimized depending on trauma center and blood bank specific logistics. Implementation of a thawed plasma program can occur with financial cost. Products with a longer shelf life, such as liquid plasma or freeze-dried plasma, may provide a more cost-effective prehospital product relative to thawed plasma., Level of Evidence: Therapeutic, level III.

Topological materials which are also superconducting are of great current interest, since they may exhibit a non-trivial topologically-mediated superconducting phase. Although there have been many reports of pressure-tuned or chemical-doping-induced superconductivity in a variety of topological materials, there have been few examples of intrinsic, ambient pressure superconductivity in a topological system having a stoichiometric composition. Here, we report that the pure intermetallic CaSn 3 not only exhibits topological fermion properties, but also has a superconducting phase at ~1.178 K under ambient pressure. The topological fermion properties, including the nearly zero quasi-particle mass and the non-trivial Berry phase accumulated in cyclotron motions, were revealed from the de Haas-van Alphen (dHvA) quantum oscillation studies of this material. Although CaSn 3 was previously reported to be superconducting with T c   =  4.2 K, our studies show that the T c   =  4.2 K superconductivity is extrinsic and caused by Sn on the degraded surface, whereas its intrinsic bulk superconducting transition occurs at 1.178 K. These findings make CaSn 3 a promising candidate for exploring new exotic states arising from the interplay between non-trivial band topology and superconductivity, e.g. topological superconductivity (TSC).

In a superconductor Cooper pairs condense into a single state and in so doing support dissipation free charge flow and perfect diamagnetism. In a magnetic field the minimum kinetic energy of the Cooper pairs increases, producing an orbital pair breaking effect. We show that it is possible to significantly quench the orbital pair breaking effect for both parallel and perpendicular magnetic fields in a thin film superconductor with lateral nanostructure on a length scale smaller than the magnetic length. By growing an ultra-thin (2 nm thick) single crystalline Pb nanowire network, we establish nm scale lateral structure without introducing weak links. Our network suppresses orbital pair breaking for both perpendicular and in-plane fields with a negligible reduction in zero-field resistive critical temperatures. Our study opens a frontier in nanoscale superconductivity by providing a strategy for maintaining pairing in strong field environments in all directions with important technological implications.

We report on a study of epitaxially grown ultrathin Pb films that are only a few atoms thick and have parallel critical magnetic fields much higher than the expected limit set by the interaction of electron spins with a magnetic field, that is, the Clogston-Chandrasekhar limit. The epitaxial thin films are classified as dirty-limit superconductors because their mean-free paths, which are limited by surface scattering, are smaller than their superconducting coherence lengths. The uniformity of superconductivity in these thin films is established by comparing scanning tunneling spectroscopy, scanning superconducting quantum interference device (SQUID) magnetometry, double-coil mutual inductance, and magneto-transport, data that provide average superfluid rigidity on length scales covering the range from microscopic to macroscopic. We argue that the survival of superconductivity at Zeeman energies much larger than the superconducting gap can be understood only as the consequence of strong spin-orbit coupling that, together with substrate-induced inversion-symmetry breaking, produces spin splitting in the normal-state energy bands that is much larger than the superconductor's energy gap., Competing Interests: The authors declare no conflict of interest.

Short rotation plantations (SRPs) are fast-growing trees (such as willow ( Salix spp.), poplar ( Populus spp.) and Eucalyptus ) grown closely together and harvested in periods of 2-20 years. There are around 50,000 hectares of SRPs in Europe, a relatively small area considering that there have been supportive policy measures in many countries for 30 years. This paper looks at the effect that the policy measures used in different EU countries have had, and how other external factors have impacted on the development of the industry. Rokwood was a 3-year European funded project which attempted to understand the obstacles and barriers facing the woody energy crops sector using well established methods of SWOT and PESTLE analysis. Stakeholder groups were formed in six different European regions to analyze the market drivers and barriers for SRP and propose ways that the industry could make progress through targeted research and development and an improved policy framework. Based upon the outcomes of the SWOT and PESTLE analysis, each region produced a series of recommendations for policymakers, public authorities, and government agencies to support the development, production, and use of SRP-derived wood fuel in each of the partner countries. This study provides details of the SRP policy analysis and reveals that each region shared a number of similarities with broad themes emerging. There is a need to educate farmers and policymakers about the multifunctional benefits of SRPs. Greater financial support from regional and/or national government is required in order to grow the SRP market. Introducing targeted subsidies as an incentive for growers could address lack of local supply chains. Long-term policy initiatives should be developed while increasing clarity within Government departments. Research funding should enable closer working between universities and industry with positive research findings developed into supportive policy measures.

Hemorrhage and trauma induced coagulopathy remain major drivers of early preventable mortality in military and civilian trauma. Interest in the use of prehospital plasma in hemorrhaging patients as a primary resuscitation agent has grown recently. Trauma center-based damage control resuscitation using early and aggressive plasma transfusion has consistently demonstrated improved outcomes in hemorrhaging patients. Additionally, plasma has been shown to have several favorable immunomodulatory effects. Preliminary evidence with prehospital plasma transfusion has demonstrated feasibility and improved short-term outcomes. Applying state-of-the-art resuscitation strategies to the civilian prehospital arena is compelling. We describe here the rationale, design, and challenges of the Prehospital Air Medical Plasma (PAMPer) trial. The primary objective is to determine the effect of prehospital plasma transfusion during air medical transport on 30-day mortality in patients at risk for traumatic hemorrhage. This study is a multicenter cluster randomized clinical trial. The trial will enroll trauma patients with profound hypotension (SBP ≤ 70 mmHg) or hypotension (SBP 71-90 mmHg) and tachycardia (HR ≥ 108 bpm) from six level I trauma center air medical transport programs. The trial will also explore the effects of prehospital plasma transfusion on the coagulation and inflammatory response following injury. The trial will be conducted under exception for informed consent for emergency research with an investigational new drug approval from the U.S. Food and Drug Administration utilizing a multipronged community consultation process. It is one of three ongoing Department of Defense-funded trials aimed at expanding our understanding of the optimal therapeutic approaches to coagulopathy in the hemorrhaging trauma patient.

Background: The objectives of this study were to evaluate the quality of national data generated by the National Breast and Cervical Cancer Early Detection Program (NBCCEDP); to assess variables collected through the program that are appropriate to use for program management, evaluation, and data analysis; and to identify potential data-quality issues., Methods: Information was abstracted randomly from 5603 medical records selected from 6 NBCCEDP-funded state programs, and 76 categorical variables and 11 text-based breast and cervical cancer screening and diagnostic variables were collected. Concordance was estimated between abstracted data and the data collected by the NBCCEDP. Overall and outcome-specific concordance was calculated for each of the key variables. Four screening performance measures also were estimated by comparing the program data with the abstracted data., Results: Basic measures of program outcomes, such as the percentage of women with cancer or with abnormal screening tests, had a high concordance rate. Variables with poor or inconsistent concordance included reported breast symptoms, receipt of fine-needle aspiration, and receipt of colposcopy with biopsy., Conclusions: The overall conclusion from this comprehensive validation project of the NBCCEDP is that, with few exceptions, the data collected from individual program sites and reported to the CDC are valid and consistent with sociodemographic and clinical data within medical records., (© 2014 American Cancer Society.)

We demonstrate that the proximity-induced exchange field H(ex) in ferromagnetic-paramagnetic bilayers can be modulated with an electric field. An electrostatic gate arrangement is used to tune the magnitude of H(ex) in the Al component of EuS/Al bilayers. In samples with H(ex)~2 T, we were able to produce modulations of ±10 mT with the application of perpendicular electric fields of the order of ±10(6) V/cm. We discuss several possible mechanisms accounting for the electric field's influence on the interfacial coupling between the Al layer and the ferromagnetic insulator EuS, along with the prospects of producing a superconducting field-effect transistor.

We present a study of the proximity effect between a ferromagnet and a paramagnetic metal of varying disorder. Thin beryllium films are deposited onto a 5 nm thick layer of the ferromagnetic insulator EuS. This bilayer arrangement induces an exchange field, H(ex), of a few tesla in low-resistance Be films with sheet resistance R≪R(Q), where R(Q)=h/e2 is the quantum resistance. We show that H(ex) survives in very high-resistance films and, in fact, appears to be relatively insensitive to the Be disorder. We exploit this fact to produce a giant low-field magnetoresistance in the correlated-insulator phase of Be films with R≫R(Q).

New distorted variants of the cubic BaHg11 structure type have been synthesized in Ga flux. Multiple phases of CePd3+xGa8-x, which include an orthorhombic Pmmn structure (x = 3.21(2)), a rhombohedral R3m structure (x = 3.13(4)), and a cubic Fm3m superstructure (x = 2.69(6)), form preferentially depending on reaction cooling rate and isolation temperature. Differential thermal analysis and in situ temperature-dependent powder X-ray diffraction patterns show a reversible phase transition at approximately 640 °C between the low temperature orthorhombic and rhombohedral structures and the high temperature cubic superstructure. Single crystal X-ray diffraction experiments indicate that the general structure of BaHg11, including the intersecting planes of a kagomé-type arrangement of Ce atoms, is only slightly distorted in the low temperature phases. A combination of Kondo, crystal electric field, and magnetic frustration effects may be present, resulting in low temperature anomalies in magnetic susceptibility, electrical resistivity, and heat capacity measurements. In addition to CePd3+xGa8-x, the rare earth analogues REPd3+xGa8-x, RE = La, Nd, Sm, Tm, and Yb, were successfully synthesized and also crystallize in one of the lower symmetry space groups.

Tunneling density of states measurements of disordered superconducting Al films in high Zeeman fields reveal a significant population of subgap states which cannot be explained by standard BCS theory. We provide a natural explanation of these excess states in terms of a novel disordered Larkin-Ovchinnikov phase that occurs near the spin-paramagnetic transition at the Chandrasekhar-Clogston critical field. The disordered Larkin-Ovchinnikov superconductor is characterized by a pairing amplitude that changes sign at domain walls. These domain walls carry magnetization and support Andreev bound states that lead to distinct spectral signatures at low energy.

We use spin-resolved electron tunneling to study the exchange field in the Al component of EuS/Al bilayers, in both the superconducting and normal-state phases of the Al. Contrary to expectation, we show that the exchange field H(ex) is a nonlinear function of applied field, even in applied fields that are well beyond the EuS coercive field. Furthermore, the magnitude H(ex) is unaffected by the superconducting phase. In addition, H(ex) decreases significantly with increasing temperature in the temperature range of 0.1-1 K. We discuss these results in the context of recent theories of generalized spin-dependent boundary conditions at a superconductor-ferromagnet interface.

Single crystals of CeM₂ and GdM₂ (M = Ag, Al, and Si) were grown by the flux growth technique and characterized by means of single crystal x-ray diffraction, magnetic susceptibility, resistivity, and heat capacity measurements. CeM₂ and GdM₂ crystallize in the tetragonal I4(1)/amd space group with the α-ThSi₂ structure type with lattice parameters a ~4.2 Å and c ~14.4 Å. Curie-Weiss behavior is observed for both analogues with CeM₂ ordering first ferromagnetically at 11 K with a second antiferromagnetic transition at 8.8 K while GdM₂ orders antiferromagnetically at 24 K. Heat capacity measurements on CeM₂ show two magnetic transitions at 10.8 and 8.8 K with an electronic specific heat coefficient, γ(0), of ~53 mJ K(-2) mol(-1). The entropy at the magnetic transition is less than the expected Rln2 for CeM₂, reinforcing the assertions of an enhanced mass state and Kondo behavior being observed in the resistivity.

We demonstrate that a distinct high-disorder anomalous Hall effect phase emerges at the correlated insulator threshold of ultrathin, amorphous, ferromagnetic CNi3 films. In the weak-localization regime, where the sheet conductance G>>e{2}/h, the anomalous Hall resistance of the films increases with increasing disorder and the Hall conductance scales as G{xy} proportional to G{phi} with phi=1.6. However, at sufficiently high disorder the system begins to enter the 2D correlated insulator regime, at which point the Hall resistance R{xy} abruptly saturates and the scaling exponent becomes phi=2. Tunneling measurements show that the saturation behavior is commensurate with the emergence of the 2D Coulomb gap, suggesting that e-e interactions mediate the high-disorder phase.

Single crystals of Ln(Cu,Al)12 and Ln(Cu,Ga)12 compounds (Ln = Y, Ce-Nd, Sm, Gd-Ho, and Yb for Al and Ln = Y, Gd-Er, Yb for Ga) have been grown by flux-growth methods and characterized by means of single-crystal x-ray diffraction, complemented with microprobe analysis, magnetic susceptibility, resistivity and heat capacity measurements. Ln(Cu,Ga)12 and Ln(Cu,Al)12 of the ThMn12 structure type crystallize in the tetragonal I4/mmm space group with lattice parameters a approximately 8.59 Å and c approximately 5.15 Å and a approximately 8.75 Å and c approximately 5.13 Å for Ga and Al containing compounds, respectively. For aluminium containing compounds, magnetic susceptibility data show Curie-Weiss paramagnetism in the Ce and Pr analogues down to 50 K with no magnetic ordering down to 3 K, whereas the Yb analogue shows a temperature-independent Pauli paramagnetism. Sm(Cu,Al)12 orders antiferromagnetically at T(N)approximately 5 K and interestingly exhibits Curie-Weiss behaviour down to 10 K with no Van Vleck contribution to the susceptibility. Specific heat data show that Ce(Cu,Al)12 is a heavy fermion antiferromagnet with T(N) approximately 2 K and with an electronic specific heat coefficient γ0 as large as 390 mJ K2 mol(-1). In addition, this is the first report of Pr(Cu,Al)12 and Sm(Cu,Al)12 showing an enhanced mass (approximately 80 and 120 mJ K(2) mol(-1)). For Ga containing analogues, magnetic susceptibility data also show the expected Curie-Weiss behaviour from Gd to Er, with the Yb analogue being once again a Pauli paramagnet. The antiferromagnetic transition temperatures range over 12.5, 13.5, 6.7, and 3.4 K for Gd, Tb, Dy, and Er. Metallic behaviour is observed down to 3 K for all Ga and Al analogues. A large positive magnetoresistance up to 150% at 9 T is also observed for Dy(Cu,Ga)12. The structure, magnetic, and transport properties of these compounds will be discussed.

We show that the pairing resonance in the Pauli-limited normal state of ultrathin superconducting Al films provides a spin-resolved probe of conduction-electron polarization in thin magnetic films. A superconductor-insulator-ferromagnet tunneling junction is used to measure the density of states in supercritical parallel magnetic fields that are well beyond the Clogston-Chandresekhar limit, thus greatly extending the field range of the tunneling density of states technique. The applicability and limitations of using the pairing resonance as a spin probe are discussed.

Allograft recipient IL-10 and/or transforming growth factor-beta (TGF-beta) dependent anti-inflammatory T-cell delayed type hypersensitivity (DTH) responses to donor derived antigens, or regulatory T-cell responses, have been demonstrated in rodents and transplant patients using a previously described trans vivo DTH assay. We used this assay to determine the incidence of recipient anti-inflammatory T-cell responses to donor antigens in a large cohort (n = 420) of primary kidney and simultaneous kidney-pancreas transplant patients tested a mean of 4.8 years after transplantation. The results were compared with clinical outcomes and the presence of detectable circulating alloantibodies. We found an unexpectedly high incidence (21.9%) of this anti-inflammatory T-cell response to donor antigens in these recipients. There was a significant correlation between this T-cell phenotype and the presence of detectable circulating alloantibodies (p = 0.03). There was no correlation between this T-cell phenotype and the degree of HLA mismatch. In addition, the presence of an anti-inflammatory DTH response to donor antigens did not correlate with an improved clinical outcome at a median of nearly 5 years after transplantation. These findings suggest that detection of an anti-inflammatory T-cell response to donor antigens does not identify patients that have developed graft protective, regulatory T-cell responses.

Donato et al. (Brevia, 20 January 2006, p. 352) concluded that logging after wildfire kills natural regeneration and increases fire risk. We argue that their paper lacks adequate context and supporting information to be clearly interpreted by scientists, resource managers, policy-makers, and the public.

We present a detailed study of the effects of interface spin-orbit coupling on the critical field behavior of ultrathin superconducting Be/Au bilayers. Parallel field measurements were made in bilayers with Be thicknesses in the range of d=2-30 nm and Au coverages of 0.5 nm. Though the Au had little effect on the superconducting gap, it produced profound changes in the spin states of the system. In particular, the parallel critical field exceeded the Clogston limit by an order of magnitude in the thinnest films studied. In addition, the parallel critical field unexpectedly scaled as [FORMULA: SEE TEXT], suggesting that the spin-orbit coupling energy was proportional to Delta0/d2. Tilted field measurements showed that, contrary to recent theory, the interface spin-orbit coupling induces a large in-plane superconducting susceptibility but only a very small transverse susceptibility.

We report a detailed study of the pairing resonance via tunneling density of states in ultrathin superconducting Al films in supercritical magnetic fields. Particular emphasis is placed on the effects of the perpendicular component of the magnetic field on the resonance energy and magnitude. Though the resonance is broadened and attenuated by H(perpendicular) as expected, its energy is shifted upward linearly with H(perpendicular). Extension of the original theory of the resonance to include strong perpendicular fields shows that at sufficiently large H(perpendicular) the overlap of the broadened resonance tail with the underlying degenerate Fermi sea alters the spectral distribution of the resonance via the exclusion principle. This leads to the shift of the resonance feature to higher energy.

We report ac susceptibility measurements of polycrystalline CePt(3)Si down to 60 mK and in applied fields up to 9 T. In a zero applied field, a full Meissner state emerges at temperatures T/T(c) < 0.3, where T(c) = 0.65 K is the onset transition temperature. Though transport measurements show a relatively high upper critical field B(c2) approximately 4-5 T, the low-temperature susceptibility chi(') is quite fragile to the applied field, with chi(') diminishing rapidly in fields of a few kG. Interestingly, the field dependence of chi(') is well described by the power law 4pichi(') + 1 = (B/B(c))(1/2), where B(c) is the field at which the onset of resistance is observed in transport measurements.

We report spin-dependent electron density of states (DOS) studies of ultrathin superconducting Al and Be films in high parallel magnetic fields. Superconductor-insulator-superconductor (SIS) tunneling spectra are presented in which both the film and the counterelectrode are in the paramagnetic limit. This SIS configuration is exquisitely sensitive to spin mixing and/or spin flip processes which are manifest as DOS singularities at eV=2 Delta(0)+/-eV(z). Both our Al and Be data show a well defined subgap peak whose magnitude grows dramatically as the parallel critical field is approached. Though this feature has previously been attributed to spin-orbit scattering, it is more consistent with fluctuations into a field induced mixed-spin state.

We have recently recognized humoral rejection (HR) in lung allograft recipients and its association with acute and chronic graft dysfunction. We have shown that C4d, a stable marker of classic complement activation, is deposited in lung allografts, correlating with clinical rejection and parenchymal injury. The antigenic target may be endothelium in the setting of recurrent acute rejection while varying components of the bronchial wall may be important in chronic graft dysfunction. We sought to establish whether there is a role for antibodies with histocompatibility antigen specificity in the lung humoral allograft phenomenon. Flow cytometric and ELISA assays to assess donor-specific antigens were conducted on sera from 25 lung transplant recipients who had experienced one or more episodes of clinical rejection; in addition, the serum samples were tested for evidence of antiendothelial cell antibody activity. Morphologically, each case had biopsies showing septal capillary injury with significant deposits of immunoreactants with microvascular localization and positive indirect immunofluorescent antiendothelial cell antibody assay. Panel-reactive antibody testing showed absence of MHC Class I/II alloantibodies; ELISA based crossmatch detecting donor-specific MHC Class I/II specific antibodies was negative. HR can occur in the absence of antibodies with HLA specificity; antigenic targets may be of endothelial cell origin.

Background: Cellular immunity is the reputed mechanism of lung allograft failure. Humoral immunity is not a commonly recognized pathway., Material and Methods: We describe 22 patients who developed a posttransplantation septal capillary injury syndrome in the absence of panel-reactive antibodies. Factor VIII levels served as an index of microvascular injury. Routine light microscopic studies were performed in a total of 73 biopsies; 54 biopsy specimens were analyzed for deposition of C1q, C4d, C5b-9, and immunoglobulin (IgG, IgM, and IgA). Indirect immunofluorescent testing to assess for antiendothelial cell antibodies was performed using patient serum and human pulmonary microvascular endothelial cell cultures as substrate. Control samples were based on patients who were clinically well at the time of the biopsy., Results: All presented with a deterioration in respiratory function. All patients had elevated factor VIII levels; the levels were significantly greater compared with pretransplantation baseline values (P =<0.03). The biopsy specimens were remarkable for septal capillary necrosis with significant septal capillary deposition of C1q, C3, C4d, and/or C5b-9 along with immunoglobulin, including IgG, with variable endothelial cell localization. The degree of septal capillary necrosis was significantly less in posttransplantation patients who were clinically doing well ( P<0.0001) as was the degree of C1q, C3, C4d, and C5b-9 ( P<0.05). Indirect antiendothelial cell antibody studies were positive in most patients. Treatment interventions included plasmapheresis, resulting in functional improvement: the postpheresis biopsy specimens showed a reduction in both the degree of septal capillary injury (P <0.0003) and the amount of C1q, C3, C4d, and C5b-9 deposition (P <0.05)., Conclusions: Septal capillary injury accompanied by direct and indirect immunofluorescent evidence of humoral immunity is a frequent finding on transbronchial biopsies. The findings suggest that humoral immunity to endothelial-based alloantigen is a common occurrence in lung grafts and may be a critical factor in chronic graft dysfunction.

Evidence of transplant recipient cellular sensitization towards donor antigens has rarely been directly measured. Rather, sensitization has been generally inferred by the presence of detectable allo-reactive or donor-reactive antibodies. In this study a newly developed delayed-type hypersensitivity assay was used to directly determine the incidence of post-transplant donor-reactive T-cell sensitization in a large cohort of kidney and simultaneous kidney-pancreas recipients. These results were compared with the presence of detectable circulating alloantibodies and with patient clinical outcome. We found an unexpectedly high incidence (52%) of donor-reactive delayed-type hypersensitivity reactivity in our study patients. Donor-reactive delayed-type hypersensitivity reactivity occurred at a much higher frequency than detectable alloantibodies (20%). Further, we found no correlation between the presence of alloantibodies and donor-reactive delayed-type hypersensitivity reactivity. We also found no correlation between the development of donor-reactive delayed-type hypersensitivity reactivity and the degree of donor and recipient HLA matching. Finally, the presence of detectable donor-reactive delayed-type hypersensitivity reactivity did not correlate with a worse clinical outcome at the time of these analyses. We conclude that in transplant recipients, the presence of circulating alloantibodies is a poor indicator of previous T-cell sensitization to donor antigens. We also conclude that our current immunosuppression strategies are relatively ineffective at blocking T-cell allosensitization, but are very effective at blocking the biological consequences of that allosensitization.

The purpose of this study was to determine the relationships between acute rejection, anti-major histocompatibility complex (MHC) class I and/or class II-reactive alloantibody production, and chronic rejection of renal allografts following kidney or simultaneous kidney-pancreas transplantation. Sera from 277 recipients were obtained pretransplant and between 1 month and 9.5 years post-transplant (mean 2.6years). The presence of anti-MHC class I and class II alloantibodies was determined by flow cytometry using beads coated with purified MHC molecules. Eighteen percent of recipients had MHC-reactive alloantibodies detected only after transplantation by this method. The majority of these patients produced alloantibodies directed at MHC class II only (68%). The incidence of anti-MHC class II, but not anti-MHC class I, alloantibodies detected post-transplant increased as the number of previous acute rejection episodes increased (p = 0.03). Multivariate analysis demonstrated that detection of MHC class II-reactive, but not MHC class I-reactive, alloantibodies post-transplant was a significant risk factor for chronic allograft rejection, independent of acute allograft rejection. We conclude that post-transplant detectable MHC class II-reactive alloantibodies and previous acute rejection episodes are independent risk factors for chronic allograft rejection. Implementing new therapeutic strategies to curtail post-transplant alloantibody production, and avoidance of acute rejection episodes, may improve long-term graft survival by reducing the incidence of chronic allograft rejection.

One of the most far-reaching problems in condensed-matter physics is to understand how interactions between electrons, and the resulting correlations, affect the electronic properties of disordered two-dimensional systems. Extensive experimental and theoretical studies have shown that interaction effects are enhanced by disorder, and that this generally results in a depletion of the density of electronic states. In the limit of strong disorder, this depletion takes the form of a complete gap in the density of states. It is known that this 'Coulomb gap' can turn a pure metal film that is highly disordered into a poorly conducting insulator, but the properties of these insulators are not well understood. Here we investigate the electronic properties of disordered beryllium films, with the aim of disentangling the effects of the Coulomb gap and the underlying disorder. We show that the gap is suppressed by a magnetic field and that this drives the strongly insulating beryllium films into a low-temperature 'quantum metal' phase with resistance near the quantum resistance RQ = h/e2, where h is Planck's constant and e is the electron charge.

We present magnetoconductance (MC) measurements of homogeneously disordered Be films whose zero field sheet conductance ( G) is described by the Efros-Shklovskii hopping law G(T) = (2e(2)/h)exp-(T0/T)(1/2). The low field MC of the films is negative with G decreasing a factor of 2 below 1 T. In contrast the MC above 1 T is strongly positive. At 8 T, G increases tenfold in perpendicular field and fivefold in parallel field. In the simpler parallel case, we observe field enhanced variable range hopping characterized by an attenuation of T0 via the Zeeman interaction.

Electron tunneling measurements of the density of states (DOS) in ultrathin Be films reveal that a correlation gap mediates their insulating behavior. In films with sheet resistance R<5000 Omega the correlation singularity appears as the usual perturbative ln(V) zero bias anomaly (ZBA) in the DOS. As R is increased further, however, the ZBA grows and begins to dominate the DOS spectrum. This evolution continues until a nonperturbative |V| Efros-Shklovskii Coulomb gap spectrum finally emerges in the highest R films. Transport measurements of films which display this gap are well described by a universal variable range hopping law R(T) = (h/2e(2))exp(T0/T)(1/2).

The complement-dependent lymphocytotoxicity crossmatch (CXM) is the presently accepted standard for detection of donor-reactive alloantibodies in transplant patients. However, the newer flow cytometric (FXM) and ELISA (EXM) crossmatch technologies are increasingly used as substitutes for the CXM. We have compared the sensitivity and reproducibility of FXM vs. EXM and, in general, find them to be quite similar. However, when we compared the agreement of FXM vs. EXM in 112 donor/recipient combinations, we found that they identified different subsets of donor-specific alloantibodies in about 35% of the tests. When compared to the standard CXM method, the EXM correlated much better than did the FXM, yielding a much lower rate of false positive (2.5% vs. 8%) and false negative (7% vs. 18.5%) results. The reduction in time required to obtain a result (3 h) and the cost of materials ($25/test) was identical for the EXM and FXM. We conclude that the ELISA method for crossmatching has advantages over the flow cytometric method as a substitute for the present standard complement-dependent lymphocytotoxicity method.

There are clinical situations in which it may be advantageous to monitor delayed type hypersensitivity (DTH) responses, an index of cell-mediated immunity, without exposing patients directly to the challenge antigens. For example, transplant patients may be at risk for becoming sensitized to donor antigens if injected with donor antigen during traditional skin tests. We describe an alternative method for human DTH testing, which involves the transfer of human peripheral blood mononuclear cells plus antigen into the pinnae or footpads of naive mice. This induces a measurable DTH-like swelling response, which we refer to as the "trans vivo DTH response." As proof of principle, we provide data obtained during trans vivo DTH studies with tetanus toxoid, cytomegalovirus (CMV) and alloantigens. In general, human T cells must be co-localized with antigen and human macrophages to produce swelling responses, and such responses are antigen-specific and require prior antigen sensitization. Not only does this assay offer a simple, reliable clinical monitoring device, but it also provides a model with which to study the in vivo mechanisms of human DTH responses.

Background: Cytomegalovirus (CMV) has been implicated as an exacerbating agent in the development of transplant vascular sclerosis; however, specific etiologic mechanisms remain unresolved. Based upon our previous observations that CMV-infected endothelial cells (ECs) stimulate proliferation and cytokine production by allogeneic T cells, we now test the hypothesis that CMV-driven cytolytic activity may contribute to graft endothelial injury., Methods: Limiting dilutions of CMV-seropositive or -seronegative donor-derived T cells were stimulated with CMV-infected or uninfected allogeneic ECs in the presence of interleukin-2. T-cell proliferation was monitored by assay of [3H]thymidine incorporation and stimulated T cells were tested for lytic activity against CMV-infected or uninfected radiolabeled EC targets by 51Cr release assay. Natural killer (NK) cell activity was examined by incubating freshly isolated peripheral blood mononuclear cells with 51Cr-labeled targets, followed by assay of radiolabel release., Results: CMV-infected ECs were resistant to T cell- and NK-mediated cytolysis regardless of donor serostatus, nature of stimulation, or level of T-cell proliferation. In contrast, although uninfected ECs were unharmed by NK cells, these targets experienced significant lysis by T cells stimulated with either uninfected or CMV-infected ECs., Conclusions: These results implicate CMV-infected graft endothelium as a persistent source of infectious virus, a chronic stimulus for potentially destructive host inflammatory activity, and a potential trigger for the generation of lytic injury to uninfected bystander endothelia, suggesting multiple mechanisms by which this virus might perturb equilibrium at the graft/host interface.

The practice of clinical and experimental transplantation continues to evolve at a rapid pace. To appreciate the current transplant practices, it is first necessary to review transplant immunology in its proper context, ie, as a component of the complex series of events that promote the repair of damaged tissues. These processes are generally categorized as inflammation, immunity, and tissue repair/reinforcement. In general, there are 3 forms of graft rejection: hyperacute, acute, and chronic rejection. All 3 forms of graft rejection represent pathologic consequences of one or more of these repair-related processes. The various graft rejection responses also illustrate several complex immunologic principles that need to be considered. These include the definition of an alloantigen, the structure and function of major histocompatibility complex molecules, and the behavior of antigen-presenting cells and alloreactive T cells. This review combines these concepts and principles into a discussion of the 3 forms of graft rejection, each of which is addressed at the level of histopathology, pathobiology, incidence, and clinical strategies.

We retrospectively compared the clinical and financial impact of a final cross-match by T cell flow cytometry (FXM) versus conventional complement-dependent cytotoxicity (CXM) in consecutive primary cadaveric kidney (K) and primary simultaneous cadaveric pancreas-kidney (SPK) transplant recipients. Mean follow-up was 14 months for both the K (range, 5-22 months) and SPK (range, 5-22 months) recipients. There were no instances of a positive CXM result if the FXM result was negative. However, 18 of the 102 (18%) K recipients and 11 of the 66 (17%) SPK recipients were FXM positive, CXM negative, but no grafts lost to hyperacute rejection in this group. In addition, patient survival, graft survival, incidence of acute rejection, and kidney and pancreas function (immediate and late) were not different in the FXM-positive versus the FXM-negative groups. Charges for the CXM and FXM methods were compared over a 6-month period. During that period, the FXM charges averaged $583 less per recipient than the CXM charges (58% reduction in charges), and the time required to perform the FXM method was 50% of that required for the CXM method. These results demonstrate that a clinical pathway for primary transplantation that utilizes the FXM rather than the CXM final cross-match is clinically safe, with no adverse effect on posttransplant outcome, reduces organ preservation time by shortening the waiting period for the final cross-match results, and significantly reduces the tissue typing charges. However, about 9% of all primary K and SPK recipients will be FXM positive, CXM negative on final cross-match and will be unnecessarily denied a transplant. In this study, we describe a method to identify these patients so that they can be tested by traditional CXM to avoid being denied access to donor organs.

Purpose: This retrospective study was undertaken to: (a) determine the prognostic significance of pretreatment and 1-year nadir serum prostate specific antigen (PSA) levels in organ-confined carcinoma of the prostate treated with ultrasound-guided radioactive 125I seed implantation; (b) determine the factors associated with postimplant morbidity and whether modification of the technique would reduce morbidity; (c) evaluate the local control rate and disease-free survival of patients undergoing seed implantation., Methods and Materials: From October 1988 through December 1992, 142 patients with organ-confined adenocarcinoma of the prostate and a Gleason score < or = 7 underwent ultrasound-guided radioactive 125I seed implantation as an alternative to radical prostatectomy. Patients were considered to have persistent or progressive disease if there was evidence of local progression on digital exam, or if there were two consecutive increases in the PSA level. Patients suspected of persistent or progressive disease underwent restaging to include CT scan of the pelvis, bone scan, and ultrasound-guided prostate biopsy. Patients with increasing PSA levels in which active disease could not be confirmed were considered biochemical failures with occult systemic disease and were offered hormone ablation., Results: With 1-6-year follow-up, median 30 months, the relapse patterns were prostate 4 (2.8%), bone 4 (2.8%), rising PSA 16 (11%). Pretreatment PSA level correlated with subsequent recurrence; pretreatment PSA < or = 4 (0), 4.1 to 10 (14%), 10.1 to 20 (21%), 20.1 to 50 (58%). Disease free survival at 2 years was 90% and at 5 years 76%. Nadir PSA (nPSA) at 1 year also correlated with recurrence: nPSA < or = 1 (3%), nPSA 1 < or = 4 (50%), and nPSA > or = 4 (100%). Seed implantation was well tolerated with 31% of patients experiencing RTOG morbidity > or = Grade 2, which typically consisted of transient radiation urethritis, which resolved with conservative measures. Eleven (8%) experienced RTOG morbidity > or = Grade 3. There was no correlation between number of seeds or total millicuries implanted and subsequent morbidity. However, reduction in the periurethral seed intensity reduced > or = Grade 3 morbidity from 11 to 4%., Conclusion: Ultrasound-guided radioactive seed implantation provides excellent local control of 97%, with a median 30 month follow-up. Morbidity is comparable to other curative modalities and by modifying Blasko's technique to reduce radioactive seed strength in the periurethral area, significant morbidity is rare. Pretreatment PSA and the nadir PSA at 1 year are important predictors of subsequent disease outcome. With a liberal definition of systemic recurrence as two consecutive increases in PSA levels, the 5-year disease-free survival is 76%.

The MLR is used clinically as a functional assay for genetic HLA disparity. Traditionally this test relies on [3H]thymidine incorporation to detect T-cell proliferation as an indicator of alloantigenicity. Environmental and administrative concerns regarding radioisotope use and disposal have encouraged the development of sensitive, nonradioactive assay for T-cell alloactivation. We describe a nonradioactive alternative to the clinical MLR which uses an IL-2-dependent cell line, CTLL20.3, and MTT reduction to detect IL-2 accumulation in MLC SNs as an index of T-cell alloactivation. We first determined (a) the optimal number of CTLL20.3 cells for the assay, (b) the optimal time of SN analysis for IL-2, and (c) additional manipulations that significantly increase the assay sensitivity for IL-2. Using this assay system with patient lymphocyte combinations, we demonstrated that the CTLL20.3-MTT assays correlate well with the [3H]thymidine assays of T-cell proliferation for the detection of MHC incompatibility. Indeed, the CTLL20.3-MTT assay may be slightly more sensitive than the traditional clinical MLR.