The transition from school to university in mathematics education research: new trends and ideas from a systematic literature review.

Investigating the transition between educational levels is one of the main themes for the future of mathematics education. In particular, the transition from secondary school to STEM degrees is problematic for the widespread students' difficulties and significant for the implications that it has on students' futures. Knowing and understanding the past is key to imagine the future of a research field. For this reason, this paper reports a systematic review of the literature on the secondary-tertiary transition in Mathematics Education from 2008 to 2021. We constructed two corpuses: one from the proceedings of three international conferences in mathematics education (PME, ICME, and INDRUM) and the other from peer reviewed research papers and book chapters returned by the databases ERIC and Google Scholar. A clear evolution in perspectives since 2008 emerges from the analysis of the two corpuses: the research focus changed from a purely cognitive to a more holistic one, including socio-cultural and - to a lesser extent - affective issues. To this end, a variety of research methods were used, and specific theoretical models were developed in the considered papers. The analysis also highlights a worrisome trend of underrepresentation: very little research comes from large geographical areas such as South America or Africa. We argue that this gap in representation is problematic as research on secondary tertiary transition concerns also consideration of socio-cultural and contextual factors.

Tales from three countries: reflections during COVID-19 for mathematical education in the future.

How can school mathematics prepare citizens for a democratic society? Answers to this question are not static; they change as society and its problems change. The SARS-CoV-2 pandemic with its corresponding disease COVID-19 presents such a problem: what is needed to navigate this complex situation that involves, among other things, mathematics? Using the essay genre, we use three narratives from three countries-Italy, the USA (California), and Germany-to reflect on the goals of teaching mathematics during this crisis and examine aspects of each country's standards for mathematics education. These three stories are framed by the authors' backgrounds, experiences, interests, their country's situation, and response to the pandemic. We first present the three narratives and then examine common issues across them that might provide insights beyond this current crisis, for preparing students to become active citizens. In particular, we focus on three issues: (1) developing a positive mindset toward mathematics to engage with and reflect on real-world problems, (2) improving interdisciplinary connections to the sciences to better understand how science professional practices and insights are similar or different from everyday practices, and (3) considering interpersonal and collective matters beyond the individual.

The oxidative phosphorylation system in mammalian mitochondria.

The chapter provides a review of the state of art of the oxidative phosphorylation system in mammalian mitochondria. The sections of the paper deal with: (i) the respiratory chain as a whole: redox centers of the chain and protonic coupling in oxidative phosphorylation (ii) atomic structure and functional mechanism of protonmotive complexes I, III, IV and V of the oxidative phosphorylation system (iii) biogenesis of oxidative phosphorylation complexes: mitochondrial import of nuclear encoded subunits, assembly of oxidative phosphorylation complexes, transcriptional factors controlling biogenesis of the complexes. This advanced knowledge of the structure, functional mechanism and biogenesis of the oxidative phosphorylation system provides a background to understand the pathological impact of genetic and acquired dysfunctions of mitochondrial oxidative phosphorylation.

Allosteric interactions and proton conducting pathways in proton pumping aa(3) oxidases: heme a as a key coupling element.

In this paper allosteric interactions in protonmotive heme aa(3) terminal oxidases of the respiratory chain are dealt with. The different lines of evidence supporting the key role of H(+)/e(-) coupling (redox Bohr effect) at the low spin heme a in the proton pump of the bovine oxidase are summarized. Results are presented showing that the I-R54M mutation in P. denitrificans aa(3) oxidase, which decreases by more than 200mV the E(m) of heme a, inhibits proton pumping. Mutational amino acid replacement in proton channels, at the negative (N) side of membrane-inserted prokaryotic aa(3) oxidases, as well as Zn(2+) binding at this site in the bovine oxidase, uncouples proton pumping. This effect appears to result from alteration of the structural/functional device, closer to the positive, opposite (P) surface, which separates pumped protons from those consumed in the reduction of O(2) to 2 H(2)O.

Inhibition of proton pumping in membrane reconstituted bovine heart cytochrome c oxidase by zinc binding at the inner matrix side.

A study is presented on the effect of zinc binding at the matrix side, on the proton pump of purified liposome reconstituted bovine heart cytochrome c oxidase (COV). Internally trapped Zn(2+) resulted in 50% decoupling of the proton pump at level flow. Analysis of the pH dependence of inhibition by internal Zn(2+) of proton release in the oxidative and reductive phases of the catalytic cycle of cytochrome c oxidase indicates that Zn(2+) suppresses two of the four proton pumping steps in the cycle, those taking place when the 2 OH(-) produced in the reduction of O(2) at the binuclear center are protonated to 2 H(2)O. This decoupling effect could be associated with Zn(2+) induced conformational alteration of an acid/base cluster linked to heme a(3).

Redox Bohr effects and the role of heme a in the proton pump of bovine heart cytochrome c oxidase.

Structural and functional observations are reviewed which provide evidence for a central role of redox Bohr effect linked to the low-spin heme a in the proton pump of bovine heart cytochrome c oxidase. Data on the membrane sidedness of Bohr protons linked to anaerobic oxido-reduction of the individual metal centers in the liposome reconstituted oxidase are analysed. Redox Bohr protons coupled to anaerobic oxido-reduction of heme a (and Cu(A)) and Cu(B) exhibit membrane vectoriality, i.e. protons are taken up from the inner space upon reduction of these centers and released in the outer space upon their oxidation. Redox Bohr protons coupled to anaerobic oxido-reduction of heme a(3) do not, on the contrary, exhibit vectorial nature: protons are exchanged only with the outer space. A model of the proton pump of the oxidase, in which redox Bohr protons linked to the low-spin heme a play a central role, is described. This article is part of a Special Issue entitled: Allosteric cooperativity in respiratory proteins.

Prospective cytomegalovirus monitoring during first-line chemotherapy in patients with acute myeloid leukemia.

Little is known about the incidence and clinical impact of cytomegalovirus (CMV) infection in patients with acute myeloid leukemia at the time of diagnosis and during chemotherapy. The aims of the present study were to assess prospectively the incidence of active CMV infection in 69 consecutive patients with acute myeloid leukemia and to describe the outcomes of treatment. pp65 antigenemia was monitored at diagnosis, post-induction and post-consolidation chemotherapy, and whenever CMV reactivation was suspected. Patients with pp65 antigenemia received pre-emptive anti-CMV treatment. Fifty-nine patients achieved complete remission. Baseline CMV serology results were available for 56 of the 59 patients: 52 patients (93%) were IgG positive. The overall incidence of pp65 antigenemia in patients in complete remission after chemotherapy was 35% (21/59): 9 patients after induction and 12 post-consolidation. Sixteen of the 21 pp65-positive patients received anti-CMV treatment: 15 as pre-emptive therapy and 1 for interstitial CMV pneumonitis. Five patients received no anti-CMV treatment and did not develop CMV disease. Patients with pp65 antigenemia had more hospital admissions (2.57 vs. 2.16; P = 0.009), while patients with >10 pp65-positive cells had more clinical complications (8/9 vs. 2/12; P = 0.002). In conclusion, patients with acute myeloid leukemia receiving chemotherapy should be monitored for active CMV infection. CMV reactivation in these patients was associated with an increased number of hospital admissions, and high levels of pp65 antigenemia were associated with more clinical complications. Controlled studies are needed to assess the relevance of pre-emptive anti-CMV therapy in patients with acute myeloid leukemia receiving chemotherapy.

Clinically driven diagnostic antifungal approach in neutropenic patients: a prospective feasibility study.

PURPOSE: Preemptive strategies in neutropenic patients based on serum galactomannan (GM) -guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening. PATIENTS AND METHODS: Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions. RESULTS: Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found. CONCLUSION: A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.

Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFalpha therapy.

BACKGROUND: Cytomegalovirus infection and disease is associated with poor prognosis and steroid refractoriness in inflammatory bowel disease patients. The unfavourable effect of steroids and immunosuppressive therapy on CMV infection is well known but few data are available concerning anti-TNFalpha therapy (Infliximab). Aim of the study was to evaluate the presence and severity of CMV infection and disease in Infliximab-treated IBD patients. PATIENTS AND METHODS: The severity of active CMV infection and disease was assessed in 11 consecutive patients with ileocolonic/colonic disease and 4 patients with ulcerative colitis before and after a standard 3-infusion course of Infliximab. Active CMV infection was evaluated by serology and diagnosed by means of pp65-antigenemia (pp65 AG), and quantification of CMV DNA isolated from biopsy specimens of colonic tissue. CMV disease was assessed on haematoxylin/eosin-stained colonic biopsies and immunohistochemical stains. RESULTS: Of the 11 patients, nine were CMV seropositive. As far as concerns CMV infection, only one patient had positive pp65 AG, before and after Infliximab. CMV DNA was detected in the colonic biopsies of three patients. In 2, CMV DNA persisted also after therapy with 410 and 1300 copies/microg of DNA, respectively, albeit with no evidence of worsening of the colonic disease. In the remaining patient, CMV DNA load became undetectable. Conventional histology and immunohistochemical stains were negative for CMV in all the patients, without evidence of CMV disease. CONCLUSIONS: Active CMV infection did not progress to disease following Infliximab therapy. Although these preliminary observations require confirmation, the response to Infliximab therapy does not appear to be influenced by, or influence the course of, CMV infection/disease.

Improving outcomes of acute invasive Aspergillus rhinosinusitis in patients with hematologic malignancies or aplastic anemia: the role of voriconazole.

We evaluated the outcomes of patients with hematologic diseases diagnosed with acute invasive Aspergillus rhinosinusitis comparing a group of patients diagnosed after voriconazole was available at our center with a historical group of patients diagnosed before voriconazole was available. Voriconazole use was associated with a decrease in mortality and earlier clinical response.

CODOX-M/IVAC (NCI 89-C-41) in children and adolescents with Burkitt's leukemia/lymphoma and large B-cell lymphomas: a 15-year monocentric experience.

During the last 15 years, we have used the National Cancer Institute (NCI) 89-C-41 protocol in patients aged younger than 21 years with Burkitt's leukemia/lymphoma (BLL) and diffuse large B-cell lymphoma (DLBCL). According to the Magrath staging system, patients were classified as low and high risk. Low-risk received three cycles of the CODOX-M regimen; high-risk patients received four alternating cycles with the CODOX-M and IVAC regimens. Thirty-five patients entered the study: 32 (91%) achieved complete remission (CR); three were non-responders and died and one patient died in CR. Two responders relapsed after 2 months and one presented early B acute lymphoblastic leukemia 33 months from the end of therapy. The 5-year overall survival and event free-survival are 83% and 80%, respectively. No late toxicity was registered. In our experience with a median follow-up of 11 years, the NCI 89-C-41 protocol has confirmed its high cure rate in BLL and DLBCL children and adolescents.

The inhibitory binding site(s) of Zn2+ in cytochrome c oxidase.

EXAFS analysis of Zn binding site(s) in bovine-heart cytochrome c oxidase and characterization of the inhibitory effect of internal zinc on respiratory activity and proton pumping of the liposome reconstituted oxidase are presented. EXAFS identifies tetrahedral coordination site(s) for Zn(2+) with two N-histidine imidazoles, one N-histidine imidazol or N-lysine and one O-COOH (glutamate or aspartate), possibly located at the entry site of the proton conducting D pathway in the oxidase and involved in inhibition of the oxygen reduction catalysis and proton pumping by internally trapped zinc.

A prospective study comparing quantitative Cytomegalovirus (CMV) polymerase chain reaction in plasma and pp65 antigenemia assay in monitoring patients after allogeneic stem cell transplantation.

BACKGROUND: Low levels of Cytomegalovirus (CMV) viral load are frequently detected following allogeneic stem cell transplantation (SCT) and CMV disease may still develop in some allogeneic SCT patients who have negative pp65-antigenemia (pp65-Ag) or undetectable DNA. Pp65Ag is a sensitive method to diagnose CMV infection. Quantitative CMV-DNA PCR assay in plasma has been proposed to monitor CMV infection in SCT patients. We evaluated the clinical utility of pp65Ag and PCR assay in plasma of SCT recipients. METHODS: In a prospective longitudinal study, 38 consecutive patients at risk of CMV infection (donor and/or recipient CMV seropositive) were weekly monitored for CMV infection by both quantitative CMV-PCR in plasma (COBAS AMPLICOR CMV MONITOR) and pp65 Ag, during the first 100 days after SCT. RESULTS: A total of 534 blood samples were simultaneously analysed for pp65Ag and PCR. Overall, 28/38 patients (74%) had active CMV infection within 100 days from SCT. In 16 patients, CMV was first detected by pp65 Ag alone; in 5 patients by both methods and in 6 by PCR assay alone; one patient had CMV biopsy-proven intestinal disease without pp65Ag and PCR assays positivity before CMV disease. Overall, three patients developed intestinal CMV disease (7.9%): one had negative both pp65Ag and PCR assays before CMV disease, one had disease and concomitant positivity of both methods, while in the remaining patient, only pp65Ag was positive before CMV disease. CONCLUSION: Plasma PCR(COBAS AMPLICOR CMV MONITOR) and pp65Ag assays were effective in detecting CMV infection, however, discordance between both methods were frequently observed. Plasma PCR and pp65Ag assays may be complementary for diagnosis and management of CMV infection.

Aspergillus galactomannan enzyme-linked immunosorbent assay cross-reactivity caused by invasive Geotrichum capitatum.

We report three cases of invasive Geotrichum capitatum infection in patients with acute leukemia for which an enzyme-linked immunosorbent assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of aspergillosis. Supernatants obtained from suspensions of 17 G. capitatum strains gave positive reactions with the Aspergillus galactomannan ELISA. These clinical and laboratory data seem to suggest that G. capitatum produces a soluble antigen that is cross-reactive with Aspergillus galactomannan.

Concerted involvement of cooperative proton-electron linkage and water production in the proton pump of cytochrome c oxidase.

In cytochrome c oxidase, oxido-reductions of heme a/Cu(A) and heme a3/Cu(B) are cooperatively linked to proton transfer at acid/base groups in the enzyme. H+/e- cooperative linkage at Fe(a3)/Cu(B) is envisaged to be involved in proton pump mechanisms confined to the binuclear center. Models have also been proposed which involve a role in proton pumping of cooperative H+/e- linkage at heme a (and Cu(A)). Observations will be presented on: (i) proton consumption in the reduction of molecular oxygen to H2O in soluble bovine heart cytochrome c oxidase; (ii) proton release/uptake associated with anaerobic oxidation/reduction of heme a/Cu(A) and heme a3/Cu(B) in the soluble oxidase; (iii) H+ release in the external phase (i.e. H+ pumping) associated with the oxidative (R-->O transition), reductive (O-->R transition) and a full catalytic cycle (R-->O-->R transition) of membrane-reconstituted cytochrome c oxidase. A model is presented in which cooperative H+/e- linkage at heme a/Cu(A) and heme a3/Cu(B) with acid/base clusters, C1 and C2 respectively, and protonmotive steps of the reduction of O2 to water are involved in proton pumping.

Candida guilliermondii fungemia in patients with hematologic malignancies.

The microbiological, clinical, and epidemiological features of most non-Candida albicans Candida species are well known, but much less is known about species such as Candida guilliermondii, an uncommon pathogen causing a variety of deep-seated infections in immunocompromised hosts. To characterize C. guilliermondii fungemia in patients with hematological malignancies and its susceptibility to antifungal drugs, all cases of C. guilliermondii fungemia diagnosed in our department between 1983 and 2005 were retrospectively analyzed and the literature was reviewed. C. guilliermondii caused 29/243 (11.7%) candidemia episodes diagnosed during the study period. Central venous catheters were the documented sources of candidemia in 19/29 episodes (65.5%), and invasive tissue infections were documented in 2 (6.9%). In the remaining eight, the catheter was not removed and the source of the fungemia remained obscure. Seven episodes ended in death, but only one could be attributed to invasive C. guilliermondii infection. Molecular typing data reveal no evidence of common infection sources. Isolates displayed high rates of in vitro susceptibility to amphotericin B (100%), voriconazole (95%), and fluconazole (90%) and lower rates of in vitro susceptibility to flucytosine (86%), itraconazole (76%), and caspofungin (33%). Our literature review confirms that C. guilliermondii is a significantly more frequent cause of candidemia among cancer patients compared with the general hospital population. It accounted for <1% of the total number of Candida bloodstream isolates reported in the articles we reviewed, with higher rates in Europe (1.4%) and Asia (1.8%) compared with North America (0.3%).

pH dependence of proton translocation in the oxidative and reductive phases of the catalytic cycle of cytochrome c oxidase. The role of H2O produced at the oxygen-reduction site.

A study is presented on the pH dependence of proton translocation in the oxidative and reductive phases of the catalytic cycle of purified cytochrome c oxidase (COX) from beef heart reconstituted in phospholipid vesicles (COV). Protons were shown to be released from COV both in the oxidative and reductive phases. In the oxidation by O2 of the fully reduced oxidase, the H+/COX ratio for proton release from COV (R --> O transition) decreased from approximately 2.4 at pH 6.5 to approximately 1.8 at pH 8.5. In the direct reduction of the fully oxidized enzyme (O --> R transition), the H+/COX ratio for proton release from COV increased from approximately 0.3 at pH 6.5 to approximately 1.6 at pH 8.5. Anaerobic oxidation by ferricyanide of the fully reduced oxidase, reconstituted in COV or in the soluble case, resulted in H+ release which exhibited, in both cases, an H+/COX ratio of 1.7-1.9 in the pH range 6.5-8.5. This H+ release associated with ferricyanide oxidation of the oxidase, in the absence of oxygen, originates evidently from deprotonation of acidic groups in the enzyme cooperatively linked to the redox state of the metal centers (redox Bohr protons). The additional H+ release (O2 versus ferricyanide oxidation) approaching 1 H+/COX at pH < or = 6.5 is associated with the reduction of O2 by the reduced metal centers. At pH > or = 8.5, this additional proton release takes place in the reductive phase of the catalytic cycle of the oxidase. The H+/COX ratio for proton release from COV in the overall catalytic cycle, oxidation by O2 of the fully reduced oxidase directly followed by re-reduction (R --> O --> R transition), exhibited a bell-shaped pH dependence approaching 4 at pH 7.2. A mechanism for the involvement in the proton pump of the oxidase of H+/e- cooperative coupling at the metal centers (redox Bohr effects) and protonmotive steps of reduction of O2 to H2O is presented.

Pulmonary infections complicating hematological disorders.

Pulmonary infections are second in importance only to septicemia as a cause of infectious morbidity and mortality in patients with hematological disorders. The differential diagnosis of the pneumonitis syndrome includes not only infection but also a multitude of noninfectious causes. In addition, the diagnosis may be difficult, owing to the subtlety of the clinical signs as a consequence of the impaired inflammatory response. Radiographic findings are often nonspecific, and invasive procedures and microbiological exams are required to establish the cause of pulmonary disease and to choose a specific therapy. However, invasive diagnostic procedures are often precluded by the poor general conditions and (particularly in acute leukemia patients) by concurrent thrombocytopenia. The approach to all infectious complications, including those of the lower respiratory tract, in immunocompromised patients with hematological diseases, is based on aggressive prevention strategies and the empirical administration of broad-spectrum antimicrobials eventually followed by a clinically or microbiologically guided treatment modification. With regard to the antimicrobial treatment, given the variety of infectious and noninfectious causes of pulmonary infiltrates in patients with hematological diseases, the diversity of the underlying immunocompromised state, and the spectrum of clinical findings, no single general therapeutic algorithm can be applied.