Successful Use of Interferon-Gamma for Refractory Disseminated Candida Tropicalis Infection in a Pediatric Patient with Acute Myeloid Leukemia and Heterozygous CARD9 Mutation

Invasive fungal infections remain among the most frequent severe and fatal complications of oncology, despite effective antifungal agents. Genetic aberrations may additionally increase the individual patient’s susceptibility to invasive mycosis, with the need for an intensified treatment, such as adjunctive immunotherapy combined with standard antifungal medication. Interferon-gamma (IFN-γ) as an immunostimulatory agent may represent a promising surrogate to reactivate the cytotoxic activity of macrophages in patients with ‘blind spots’. We report the case of a pediatric patient with AML and disseminated candida tropicalis infection, bearing a heterozygous CARD9 mutation, who was treated successfully with combined IFN-γ and conventional antifungal therapy

Impact of Rotational Twin Boundaries and Lattice Mismatch on III-V Nanowire Growth

Pseudomorphic planar III-V transition layers greatly facilitate the epitaxial integration of vapor liquid solid grown III-V nanowires (NW) on Si(111) substrates. Heteroepitaxial (111) layer growth, however, is commonly accompanied by the formation of rotational twins. We find that rotational twin boundaries (RTBs), which intersect the surface of GaP/Si(111) heterosubstrates, generally cause horizontal NW growth and may even suppress NW growth entirely. Away from RTBs, the NW growth direction switches from horizontal to vertical in the case of homoepitaxial GaP NWs, whereas heteroepitaxial GaAs NWs continue growing horizontally. To understand this rich phenomenology, we develop a model based on classical nucleation theory. Independent of the occurrence of RTBs and specific transition layers, our model can generally explain the prevalent observation of horizontal III V NW growth-in lattice mismatched systems and the high crystal quality of horizontal nanowires.This work was financially supported by the BMBF (Project No. 03SF0404A) and partly by the Spanish Ministry of Economy (Project TEC2014-54260-C3-2-P). C.K. and L.W. acknowledge the Thuringia Graduate School for Photovoltaics “Photograd” for financial support. The authors would like to thank A. Paszuk and A. Nagelein for valuable discussions as well as A. Muller and M. Biester for technical support, T. Nieszner for supporting the determination of the spatial direction of NWs, and D. Roßberg for preparing the TEM lamella

Laser-induced acceleration of Helium ions from unpolarized gas jets

In order to develop a laser-driven spin-polarized ³He-ion beam source available for nuclear-physics experiments as well as for the investigation of polarized nuclear fusion, several challenges have to be overcome. Apart from the provision of a properly polarized ³He gas-jet target, one of the biggest milestones is the demonstration of the general feasibility of laser-induced ion acceleration out of gas-jet targets. Of particular importance is the knowledge about the main ion-emission angles as well as the achievable ion-energy spectra (dependent on the optimal set of laser and target parameters). We report on the results of such a feasibility study performed at PHELIX, GSI Darmstadt. Both ³He- and ⁴He-gas jets (ngas ∼ 10¹⁹ cm⁻³) were illuminated with high-intensity laser pulses, IL ∼ O (10¹⁹ W cm⁻²). The main ion-emission angles could be identified (±90° with respect to the laser-propagation direction) and the ion-energy spectra for all ion species could be extracted: for the optimal laser and target parameters, the high-energy cut-offs for He ²⁺,¹⁺ ions were 4.65 MeV (with a normalized energy uncertainty of Δ ɛ​ ɛ​⁻¹ = 0.033) and 3.27 MeV (Δ ɛ​ ɛ​⁻¹= 0.055), respectively

Personalized Medicine for Pediatric AML: New Targeted StrategiesTopics in Anti-Cancer Research

Acute myeloid leukemia is a heterogeneous group of diseases accounting for 15- 20% of all tumors diagnosed in children under 15 years of age. The past few decades have yielded remarkable improvements in long-term outcomes for children with acute myeloid leukemia. A better risk-group stratification of patients based upon clinical and biologic features, a more effective use of anti-leukemic agents and enormous improvements in supportive care have increased the probability of cure by approximately 60%. The increase in our understanding of the biology of this disease has resulted in the development of molecularly targeted therapies that are potentially more effective and less toxic than the standard approaches. We here review novel molecularly targeted drugs for the treatment of childhood acute myeloid leukemia such as monoclonal antibodies, inhibitors of signalling molecules, proteasome inhibitors and epigenetic agents. For these recently patented agents, we also provide a detailed analysis of the published preclinical data and the clinical trials that have been completed

Molluscum contagiosum infection on a congenital intermediate melanocytic naevus

A 2-year-old girl presented with a 3-month history of several small painless papules, growing on the surface of an abdominal congenital melanocytic naevus (MN). Her mother noted that the lesions were significantly increasing in number and size. There was no history of trauma and her medical and family histories were unremarkable. Physical examination revealed multiple skin-coloured, translucent, glossy, dome-shaped papules, ranging from 1 to 3\u2005mm, localised exclusively on the surface of a macular, smooth, light to dark brown, non-hypertrichotic congenital intermediate MN (2 74\u2005cm) (see figure 1). The dermoscopic examination of the papules suggested the diagnosis of molluscum contagiosum (MC), which was histologically confirmed. MC is a common viral skin infection, which is seldom associated with other skin diseases (eg, epidermoid cyst and nevocellular naevus).1 The localisation of MC on an MN is extremely rare, and only a few case reports have been published in the literature until now; in all reported cases, the lesions are strictly confined to the MN and did not affect the remaining skin.2 ,3 A possible explanation of the occurrence of viral lesions on an MN may be represented by the Meyerson\u2019s phenomenon, an eczematous reaction occurring in MN.4 We could hypothesise that this resulted in a barrier dysfunction predisposing the patient to develop MC locally. Even though congenital intermediate MN is recognised to have a low malignancy potential during childhood,5 melanoma can develop. Therefore, the physician should be aware of the appearance of MC superinfection on MN, but the occurrence of new lesions within a congenital MN requires a dermatological evaluatio

T-Cell-Replete Versus ex vivo T-Cell-Depleted Haploidentical Haematopoietic Stem Cell Transplantation in Children With Acute Lymphoblastic Leukaemia and Other Haematological Malignancies

Allogeneic haematopoietic stem cell transplantation (HSCT) represents a potentially curative option for children with high-risk or refractory/relapsed leukaemias. Traditional donor hierarchy favours a human leukocyte antigen (HLA)-matched sibling donor (MSD) over an HLA-matched unrelated donor (MUD), followed by alternative donors such as haploidentical donors or unrelated cord blood. However, haploidentical HSCT (hHSCT) may be entailed with significant advantages: besides a potentially increased graft-vs.-leukaemia effect, the immediate availability of a relative as well as the possibility of a second donation for additional cellular therapies may impact on outcome. The key question in hHSCT is how, and how deeply, to deplete donor T-cells. More T cells in the graft confer faster immune reconstitution with consecutively lower infection rates, however, greater numbers of T-cells might be associated with higher rates of graft-vs.-host disease (GvHD). Two different methods for reduction of alloreactivity have been established: in vivo T-cell suppression and ex vivo T-cell depletion (TCD). Ex vivo TCD of the graft uses either positive selection or negative depletion of graft cells before infusion. In contrast, T-cell-repleted grafts consisting of non-manipulated bone marrow or peripheral blood grafts require intense in vivo GvHD prophylaxis. There are two major T-cell replete protocols: one is based on post-transplantation cyclophosphamide (PTCy), while the other is based on anti-thymocyte globulin (ATG; Beijing protocol). Published data do not show an unequivocal benefit for one of these three platforms in terms of overall survival, non-relapse mortality or disease recurrence. In this review, we discuss the pros and cons of these three different approaches to hHSCT with an emphasis on the significance of the existing data for children with acute lymphoblastic leukaemia

Impact of N Incorporation on VLS Growth of GaP(N) Nanowires Utilizing UDMH

Abstract III–V nanowires (NWs) possess great potential for use in future semiconductor technology. Alloying with dilute amounts of nitrogen provides further flexibility in tuning their material properties. In this study, we report on successful in situ nitrogen incorporation into GaP(N) NWs during growth via the Au-catalyzed vapor-liquid-solid (VLS) mechanism. The impact of the nitrogen precursur unsymmetrical dimethyl hydrazine (UDMH) on morphology was found to be overall beneficial as it strongly reduces tapering. Analysis of the crystal structure of NWs with and without N reveals zinc blende structure with an intermediate amount of stacking faults (SF). Interestingly, N incorporation leads to segments completely free of SFs, which are related to dislocations transverse to the growth direction

Towards a Laser-driven polarized 3He Ion-Beam Source

In order to investigate the polarization degree of laser-accelerated 3He ions from a pre-polarized 3He gas-jet target, several challenges have to be overcome beforehand. One of these includes the demonstration of the feasibility of laser-induced ion acceleration out of gas-jet targets. In particular, the ion-emission angles as well as the ion-energy spectra have to be determined for future polarization measurements. Such an experiment was performed at the PHELIX Petawatt Laser Facility, GSI Darmstadt. As laser target, both 4He, and in a second step, unpolarized 3He gas were applied