Combination therapy with rituximab, low-dose cyclophosphamide, and prednisone for idiopathic membranous nephropathy: a case series

BACKGROUND: Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. METHODS: We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline. Complete remission was defined as a UPCR < 0.3 g/g. Secondary outcomes were serious adverse events and the change in proteinuria, serum creatinine, serum albumin, cholesterol, triglycerides, and immunoglobulin G levels after 1 year of treatment. RESULTS: Over a median follow-up time of 37 (IQR, 34-44) months, 100% of patients achieved partial remission and 93% of patients achieved complete remission at a median time of 2 and 13 months, respectively. After 1 year of treatment, median (IQR) UPCR declined from 8.2 (6.6-11.1) to 0.3 (0.2-0.7) g/g (P < 0.001). Three serious adverse events occurred over 51 patient years. No patients died or progressed to ESKD. CONCLUSIONS: Treatment of idiopathic membranous nephropathy with RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted

Gaugino Condensation in M-theory on S^1/Z_2

In the low energy limit of for M-theory on S^1/Z_2, we calculate the gaugino condensate potential in four dimensions using the background solutions due to Horava. We show that this potential is free of delta-function singularities and has the same form as the potential in the weakly coupled heterotic string. A general flux quantization rule for the three-form field of M-theory on S^1/Z_2 is given and checked in certain limiting cases. This rule is used to fix the free parameter in the potential originating from a zero mode of the form field. Finally, we calculate soft supersymmetry breaking terms. We find that corrections to the Kahler potential and the gauge kinetic function, which can be large in the strongly coupled region, contribute significantly to certain soft terms. In particular, for supersymmetry breaking in the T-modulus direction, the small values of gaugino masses and trilinear couplings that occur in the weakly coupled, large radius regime are enhanced to order m_3/2 in M-theory. The scalar soft masses remain small even, in the strong coupling M-theory limit.Comment: 20 pages, LATE

A floristic survey of Yucca Mountain and vicinity, Nye County, Nevada

A survey of the vascular flora of Yucca Mountain and vicinity, Nye County, Nevada, was conducted from March to June 1994. An annotated checklist of recorded taxa was compiled. Voucher plant specimens were collected and accessioned into the Herbarium at the University of Nevada, Las Vegas. Collection data accompanying these specimens were entered into that herbarium`s electronic data base. Combined results from this survey and the works of other investigators reveal the presence of a total of 325 specific and intraspecific taxa within the area, these allocated to 162 genera and 53 families. Owing to drought conditions prevalent throughout the area, the annual floristic component was largely absent during the period of study, and it is likely much under-represented in the tabulation of results. No taxon currently listed as threatened or endangered under the Endangered Species Act was encountered during this study. Several candidate species for listing under this Act were present, and distributional data for these were recorded. No change in the status of these candidate species is recommended as the result of this survey

RR-Parity Violation in Flavor Changing Neutral Current Processes and Top Quark Decays

We show that supersymmetric $R$-parity breaking ($\not R_p$) interactions always result in Flavor Changing Neutral Current (FCNC) processes. Within a single coupling scheme, these processes can be avoided in either the charge $+2/3$ or the charge $-1/3$ quark sector, but not both. These processes are used to place constraints on \Rp couplings. The constraints on the first and the second generations are better than those existing in the literature. The \Rp interactions may result in new top quark decays. Some of these violate electron-muon universality or produce a surplus of $b$ quark events in $t\bar{t}$ decays. Results from the CDF experiment are used to bound these \Rp couplings.Comment: LaTeX, 20 pages, spelling corrected from origina

Climate impacts associated with reduced diet diversity in children across nineteen countries

It is widely anticipated that climate change will negatively affect both food security and diet diversity. Diet diversity is especially critical for children as it correlates with macro and micronutrient intake important for child development. Despite these anticipated links, little empirical evidence has demonstrated a relationship between diet diversity and climate change, especially across large datasets spanning multiple global regions. Here we use survey data from 19 countries and more than 107,000 children, coupled with 30 years of precipitation and temperature data, to explore the relationship of climate to child diet diversity while controlling for other agroecological, geographic, and socioeconomic factors. We find that higher long-term temperatures are associated with decreases in overall child diet diversity, while higher rainfall in the previous year, compared to the long-term average, is associated with greater diet diversity. Examining six regions individually, we find that five have significant reductions in diet diversity associated with higher temperatures while three have significant increases in diet diversity associated with higher precipitation. In some regions, the statistical effect of climate on diet diversity is comparable to or greater than other common development efforts including those focused on education, improved water and toilets, and poverty reduction. These results suggest that warming temperatures and increasing rainfall variability could have profound short- and long-term impacts on child diet diversity, potentially undermining widespread development interventions aimed at improving food security

Renormalization Group Induced Neutrino Mass in Supersymmetry without R-parity

We study supersymmetric models without R parity and with universal soft supersymmetry breaking terms. We show that as a result of the renormalization group flow of the parameters, a misalignment between the directions in field space of the down-type Higgs vacuum expectation value $v_d$ and of the $\mu$ term is always generated. This misalignment induces a mixing between the neutrinos and the neutralinos, resulting in one massive neutrino. By means of a simple approximate analytical expression, we study the dependence on the different parameters that contribute to the misalignment and to $m_\nu$. In large part of the parameter space this effect dominates over the standard one-loop contributions to $m_\nu$; we estimate 1 MeV \lsim m_\nu \lsim 1 GeV. Laboratory, cosmological and astrophysical constraints imply m_\nu \lsim 100 eV. To be phenomenologically viable, these models must be supplemented with some additional mechanism to ensure approximate alignment and to suppress $m_\nu$.Comment: 21 pages, LaTex. Few points clarified, results unchanged. Final version to appear on Physical Review

Models of Neutrino Masses and Baryogenesis

Majorana masses of the neutrino implies lepton number violation and is intimately related to the lepton asymmetry of the universe, which gets related to the baryon asymmetry of the universe in the presence of the sphalerons during the electroweak phase transition. Assuming that the baryon asymmetry of the universe is generated before the electroweak phase transition, it is possible to dicriminate different classes of models of neutrino masses. While see-saw mechanism and the triplet higgs mechanism are preferred, the Zee-type radiative models and the R-parity breaking models requires additional inputs to generate baryon asymmetry of the universe during the electroweak phase transition.Comment: 27 pages including 5 figures; Review article for Pramana: the Indian Journal of Physic

Low-Scale See-Saw Mechanisms for Light Neutrinos

Alternatives to the see-saw mechanism are explored in supersymmetric models with three right-handed or sterile neutrinos. Tree-level Yukawa couplings can be drastically suppressed in a natural way to give sub-eV Dirac neutrino masses. If, in addition, a B-L gauge symmetry broken at a large scale M_G is introduced, a wider range of possibilities opens up. The value of the right-handed neutrino mass M_R can be easily disentangled from that of M_G. Dirac and Majorana neutrino masses at the eV scale can be generated radiatively through the exchange of sneutrinos and neutralinos. Dirac masses m_D owe their smallness to the pattern of light-heavy scales in the neutralino mass matrix. The smallness of the Majorana masses m_L is linked to a similar see-saw pattern in the sneutrino mass matrix. Two distinct scenarios emerge. In the first, with very small or vanishing M_R, the physical neutrino eigenstates are, for each generation, either two light Majorana states with mixing angle ranging from very small to maximal, depending on the ratio m_D/M_R, or one light Dirac state. In the second scenario, with a large value of M_R, the physical eigenstates are two nearly unmixed Majorana states with masses \sim m_L and \sim M_R. In both cases, the (B-L)-breaking scale M_G is, in general, much smaller than that in the traditional see-saw mechanism.Comment: 31 pages, Latex, references added, version to appear in Phys. Rev.

Neovascularized implantable cell homing encapsulation platform with tunable local immunosuppressant delivery for allogeneic cell transplantation.

Cell encapsulation is an attractive transplantation strategy to treat endocrine disorders. Transplanted cells offer a dynamic and stimulus-responsive system that secretes therapeutics based on patient need. Despite significant advancements, a challenge in allogeneic cell encapsulation is maintaining sufficient oxygen and nutrient exchange, while providing protection from the host immune system. To this end, we developed a subcutaneously implantable dual-reservoir encapsulation system integrating in situ prevascularization and local immunosuppressant delivery, termed NICHE. NICHE structure is 3D-printed in biocompatible polyamide 2200 and comprises of independent cell and drug reservoirs separated by a nanoporous membrane for sustained local release of immunosuppressant. Here we present the development and characterization of NICHE, as well as efficacy validation for allogeneic cell transplantation in an immunocompetent rat model. We established biocompatibility and mechanical stability of NICHE. Further, NICHE vascularization was achieved with the aid of mesenchymal stem cells. Our study demonstrated sustained local elution of immunosuppressant (CTLA4Ig) into the cell reservoir protected transcutaneously-transplanted allogeneic Leydig cells from host immune destruction during a 31-day study, and reduced systemic drug exposure by 12-fold. In summary, NICHE is the first encapsulation platform achieving both in situ vascularization and immunosuppressant delivery, presenting a viable strategy for allogeneic cell transplantation

Multiple Smaller Missions as a Direct Pathway to Mars Sample Return

Recent discoveries by the Mars Exploration Rovers, Mars Express, Mars Odyssey, and Mars Reconnaissance Orbiter spacecraft include multiple, tantalizing astrobiological targets representing both past and present environments on Mars. The most desirable path to Mars Sample Return (MSR) would be to collect and return samples from that site which provides the clearest examples of the variety of rock types considered a high priority for sample return (pristine igneous, sedimentary, and hydrothermal). Here we propose an MSR architecture in which the next steps (potentially launched in 2018) would entail a series of smaller missions, including caching, to multiple landing sites to verify the presence of high priority sample return targets through in situ analyses. This alternative architecture to one flagship-class sample caching mission to a single site would preserve a direct path to MSR as stipulated by the Planetary Decadal Survey, while permitting investigation of diverse deposit types and providing comparison of the site of returned samples to other aqueous environments on early Mar