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\"This book presents recent advancements in positive psychology, specifically its application across broad areas of current interest. Chapters include submissions from various international authors in the field and cover discussion and presentation of relevant research, theories, and applications. The volume covers topics such as CBT, Psychotherapy, Coaching, Workplaces, Aging, Education, Leadership, Emotion, Interventions, Measurement, Technology, Design, Health, Relationships, Experiences, Communities. With the growing interest in the applications of positive psychology across diverse fields within psychology and beyond, this book will make a worthwhile contribution to the field. It will also fill the current need for a volume that highlights specifically the various recent advancements in positive psychology into diverse fields and as such will be of benefit to a wide range of professionals, including psychologists, educators, clinicians, therapists, and many others.\" -- Publisher's website.

Arsenic trioxide (ATO) is presently the most active single agent in the treatment of acute promyelocytic leukemia (APL). This review provides insights into the mode of action and the pharmacological properties of ATO, and summarizes the most relevant results of more than 20 treatment studies in relapsed or newly diagnosed APL published between 1997 and 2011. ATO acts by targeting multiple pathways in APL leading to apoptosis and myeloid differentiation. It induces complete remission without myelosuppression and causes only few adverse effects. In relapsed APL, ATO-based salvage therapy has been able to induce long-lasting remissions and possible cure in 50–81% of patients. In newly diagnosed APL, two main strategies are currently pursued. ATO is either included into induction therapy with the aim to minimize or eliminate chemotherapy, or it is incorporated as an additive into established first-line concepts with all- trans -retinoic acid and chemotherapy to reinforce their anti-leukemic efficacy. Recent results suggest a high efficacy of ATO in both concepts. In conclusion, experimental research and clinical studies have made contributions toward a better understanding of the molecular mechanisms induced by ATO in APL cells and have established this historic substance as an important candidate for the further improvement of APL therapy.

To explore the molecular profile and its prognostic implication in systemic mastocytosis (SM), we analyzed the mutation status of granulocyte–macrophage colony-forming progenitor cells (CFU-GM) in patients with KIT D816V + indolent SM (ISM, n =4), smoldering SM (SSM, n =2), aggressive SM (ASM, n =1), SM with associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n =5) and ASM-AHNMD ( n =7). All patients with (A)SM-AHNMD ( n =12) carried 1–4 (median 3) additional mutations in 11 genes tested, most frequently TET2 , SRSF2 , ASXL1 , CBL and EZH2 . In multi-mutated (A)SM-AHNMD, KIT D816V + single-cell-derived CFU-GM colonies were identified in 8/12 patients (median 60%, range 0–95). Additional mutations were identified in CFU-GM colonies in all patients, and logical hierarchy analysis indicated that mutations in TET2 , SRSF2 and ASXL1 preceded KIT D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were exclusively KIT D816V − . These data indicate that (a) (A)SM-AHNMD is a multi-mutated neoplasm, (b) mutations in TET2 , SRSF2 or ASXL1 precede KIT D816V in ASM-AHNMD, (c) KIT D816V is thus a phenotype modifier toward SM and (d) KIT D816V or other mutations are rare in CFU-GM colonies of ISM/SSM patients, which might explain at least in part their better prognosis.

Invasive pulmonary aspergillosis (IPA) is an emerging and life-threatening infectious disease in patients admitted to the intensive care unit (ICU). Most diagnostic studies are conducted in hematological patients and results cannot readily be transferred to ICU patients lacking classical host factors. In a multicenter, prospective clinical trial including 44 ICU patients, hematological (n = 14) and non-hematological patients (n = 30), concurrent serum and bronchoalveolar lavage (BAL) samples were analyzed by conventional culture, galactomannan (GM), 1-3-beta-D-glucan (BDG) as well as an Aspergillus specific nested polymerase chain reaction (PCR). Nine patients (20%) had putative IPA according to AspICU classification. GM and PCR showed superior performance in BAL with sensitivity/specificity of 56%/94% and 44%/94% compared to 33%/97% and 11%/94% in serum. Despite better sensitivity of 89%, BDG showed poor specificity of only 31% (BAL) and 26% (serum). Combination of GM and PCR (BAL) with BDG (serum) resulted in 100% sensitivity, but also reduced specificity to 23%. Whereas mean GM levels were significantly higher in hematological patients BDG and PCR did not differ between hematological and non-hematological patients. Under present clinical conditions test combinations integrating both BAL and blood samples are advantageous. BDG might best serve as possible indicator for ruling out IPA. ClinicalTrials.gov Identifier: NCT01695499. First posted: September 28, 2012, last update posted: May 8, 2017. •Combination of galactomannan (GM), beta-d-glucan (BDG) and Aspergillus PCR•Test combinations showed superior compared to single tests•Combining bronchoalveolar lavage and serum samples is beneficial•Low specificity of BDG limits its diagnostic value in intensive care patients•GM levels were significantly higher in hematological patients

Most efforts to characterize the size and composition of the mantle that complements the continental crust have assumed that the mid‐ocean ridge basalt (MORB) source is the incompatible‐element depleted residue of continental crust extraction. The use of Nd isotopes to model this process led to the conclusion that the “depleted MORB reservoir” is confined to the upper ∼30% of the mantle, leaving the lower mantle in a more “primitive” state. Here, we use Nb/U and Ta/U to evaluate mass and composition of the mantle reservoir residual to continent extraction and find that it exceeds 60% of the total mantle. Thus, the (Nb, Ta)/U‐based mass balance conflicts with the ε(Nd)‐based mass balance, and this invalidates the classical 3‐reservoir silicate Earth model (continental crust, depleted mantle, and primitive mantle). Including the combined MORB + ocean island basalt (OIB) sources in the ε(Nd)‐based mass balance does not reconcile the conflict as it would require their average ε(Nd) to be ≤3.0, much lower than observed MORB + OIB ε(Nd) averages. We resolve this conflict by invoking an additional, “early enriched reservoir” (EER), formed prior to extraction of significant continental crust, but now hidden or lost. This EER differs from EERs previously invoked by having no Nb‐Ta anomaly. We suggest that it originated as an early mafic crust, which had unfractionated (Nb, Ta)/U but fractionated Sm/Nd ratios. The corresponding “early depleted” reservoir generated the present‐day continental crust and the “residual mantle” MORB‐OIB reservoir, which occupies at least 63% of the present‐day mantle and is only moderately depleted in incompatible trace elements. Plain Language Summary The Earth's continental crust makes up only about half a percent of Earth's mass, but it contains a large portion of its total budget of uranium and thorium, which produce much of Earth's interior heat. In making the crust, these elements have been extracted via melts and volcanism from Earth's mantle. But what portion of the mantle was involved in making the continents? Previously, geochemists concluded that only its uppermost 30% was involved, leaving the lower two‐thirds of the mantle essentially untouched. The measure used for this estimate has been the difference in the isotope ratios of neodymium, 143Nd/144Nd, between crust and mantle. However, when we use an alternative measure for the same calculation, namely the ratio of niobium to uranium, Nb/U, we find the depleted mantle fraction to be greater than 60%. We therefore need an Earth model that involves an additional “reservoir” with crust‐like Nd isotopes but mantle‐like Nb/U. We model this as an early Earth basaltic crust, which may have been lost to space, or may now be hidden at the base of the mantle. A buried ancient crust might well explain the large density/temperature anomalies recently discovered at the base of the mantle by seismologists. Key Points A new assessment of the depleted mantle (DM) mass (>63%) based on (Nb, Ta)/U conflicts with conventional estimates using Nd isotopes (<50%) This invalidates the classic 3‐reservoir silicate Earth (continental crust, DM, and primitive mantle) The observable, present‐day mantle was permanently depleted by segregation or loss of an early enriched reservoir

Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. Results: (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P =0.001); (iii) at 3 months, a 6% BCR-ABL IS cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P =0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

CO 2 is considered to play a key role in the melting of the deep upper mantle, and carbonated silicate melts have been widely predicted by partial melting experiments to exist at mantle depths of greater than 80 km. However, such melts have not been shown to exist in nature. Thus, the relationship between CO 2 and the origin of silicate melts is highly speculative. Here we present geochemical analyses of rocks sampled from the South China Sea, at the Integrated Ocean Discovery Program Site U1431. We identify natural carbonated silicate melts, which are enriched in light rare earth elements and depleted in Nb and Ta, and show that they were continuously transformed to alkali basalts that are less enriched in light rare earth elements and enriched in Nb and Ta. This shows that carbonated silicate melts can survive in the shallow mantle and penetrate through the hot asthenosphere. Carbonated silicate melts were converted to alkali basaltic melts through reactions with the lithospheric mantle, during which precipitation of apatite accounts for reduction of light rare earth elements and genesis of positive Nb–Ta anomalies. We propose that an extremely thin lithosphere (less than 20 km in the South China Sea) facilitates extrusion of the carbonated silicate melts, whereas a thickened lithosphere tends to modify carbonated silicate melt to alkali basalt. Carbonated silicate melts are expected to exist in the mantle, but have been elusive in nature. Geochemical analyses of rocks from the South China Sea identify such melts formed in the mantle and erupted at the surface through thin lithosphere.

Aberrant aggregation of the RNA-binding protein TDP-43 in neurons is a hallmark of frontotemporal lobar degeneration caused by haploinsufficiency in the gene encoding progranulin 1 , 2 . However, the mechanism leading to TDP-43 proteinopathy remains unclear. Here we use single-nucleus RNA sequencing to show that progranulin deficiency promotes microglial transition from a homeostatic to a disease-specific state that causes endolysosomal dysfunction and neurodegeneration in mice. These defects persist even when Grn −/− microglia are cultured ex vivo. In addition, single-nucleus RNA sequencing reveals selective loss of excitatory neurons at disease end-stage, which is characterized by prominent nuclear and cytoplasmic TDP-43 granules and nuclear pore defects. Remarkably, conditioned media from Grn −/− microglia are sufficient to promote TDP-43 granule formation, nuclear pore defects and cell death in excitatory neurons via the complement activation pathway. Consistent with these results, deletion of the genes encoding C1qa and C3 mitigates microglial toxicity and rescues TDP-43 proteinopathy and neurodegeneration. These results uncover previously unappreciated contributions of chronic microglial toxicity to TDP-43 proteinopathy during neurodegeneration. In the absence of progranulin, microglia enter a disease-specific state that causes endolysosomal dysfunction and neurodegeneration, and these microglia promote TDP-43 granule formation, nuclear pore defects and cell death specifically in excitatory neurons via the complement activation pathway.

Invasive pulmonary aspergillosis (IPA) is one of the major complications in immunocompromised patients. The mainstay of diagnostic imaging is non-enhanced chest-computed-tomography (CT), for which various non-specific signs for IPA have been described. However, contrast-enhanced CT pulmonary angiography (CTPA) has shown promising results, as the vessel occlusion sign (VOS) seems to be more sensitive and specific for IPA in hematologic patients. The aim of this study was to evaluate the diagnostic accuracy of CTPA in a larger cohort including non-hematologic immunocompromised patients. CTPA studies of 78 consecutive immunocompromised patients with proven/probable IPA were analyzed. 45 immunocompromised patients without IPA served as a control group. Diagnostic performance of CTPA-detected VOS and of radiological signs that do not require contrast-media were analyzed. Of 12 evaluable radiological signs, five were found to be significantly associated with IPA. The VOS showed the highest diagnostic performance with a sensitivity of 0.94, specificity of 0.71 and a diagnostic odds-ratio of 36.8. Regression analysis revealed the two strongest independent radiological predictors for IPA to be the VOS and the halo sign. The VOS is highly suggestive for IPA in immunocompromised patients in general. Thus, contrast-enhanced CTPA superior over non-contrast_enhanced chest-CT in patients with suspected IPA.

Carbonate, the major carbon reservoir on Earth’s surface, can enter into the mantle by subduction. However, evidence for recycled surficial carbonates in the deep mantle is still scarce. Ocean island basalts from Cook-Austral islands and St. Helena Island, widely called HIMU basalts because of their high μ =  238 U/ 204 Pb sources, are thought to be fed by mantle plumes originating in the lower mantle. Here we report exceptionally high δ 66 Zn values (δ 66 Zn = 0.38 ± 0.03‰) of these HIMU lavas relative to most published data for oceanic basalts (δ 66 Zn = 0.31 ± 0.10‰), which requires a source contributed by isotopically heavy recycled surficial carbonates. During subduction of the oceanic lithosphere, melting of mixed surficial carbonates and basaltic crust in the deep mantle generates carbonatite melts, which metasomatizes the nearby mantle and the resultant carbonated mantle ultimately evolves into a high-δ 66 Zn HIMU source. High-δ 66 Zn signatures of HIMU basalts, therefore, demonstrate that carbonates can be transported into Earth’s deep mantle. Zhang et al. perform high-precision zinc (Zn) isotopic analysis on lavas from St. Helena Island in the Atlantic, and Cook-Austral Islands in the Pacific, and confirm that ancient superficial carbonates were transported into the deep mantle billions of years ago.