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.

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.

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.

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.

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

BACKGROUND: The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. METHODS: We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). RESULTS: An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. CONCLUSIONS: Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known.

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.

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.

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.

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.

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.

The role of real-time ultrasonography in predicting esophageal varices in hemophiliacs co-infected with hepatitis C and human immunodeficiency virus.

BACKGROUND AND OBJECTIVES: Endoscopic procedures are the gold standard for the diagnosis of esophageal varices but these invasive methods are complex to perform in hemophilic patients co-infected with hepatitis C virus/human immunodeficiency virus (HCV/HIV). Real-time ultrasonography has been reported to be an effective, non-invasive procedure able to monitor patients with chronic liver disease and to give useful information for the diagnosis of liver cirrhosis, portal hypertension and the presence of esophageal varices. DESIGN AND METHODS: Seventy patients with severe hemophilia were evaluated by esophago-gastro-duodenoscopy (EGDS) and ultrasonography; 40 had HCV/HIV co-infection and 30, comparable for age and HCV exposure time, were HCV+/HIV-. Hepatic longitudinal diameter, splenic longitudinal diameter, portal vein diameter and the average speed of portal flow were measured. The congestion index was calculated. RESULTS: Thirteen out of 40 (32.5%) HCV/HIV coinfected patients had esophageal varices. None out of 30 HCV+/HIV- patients had esophageal varices (p< 0.001). Univariate analysis showed that the 13 HCV/HIV coinfected patients with esophageal varices had significantly higher hepatic longitudinal diameter (p=0.006), splenic longitudinal diameter (p=0.0002), portal vein diameter (p=0.0005) and congestion index (p=0.0001) than did the remaining 27 HCV/HIV coinfected patients. The stepwise logistic regression analysis indicated that, of the various ultrasonographic parameters evaluated, splenic longitudinal diameter and portal vein diameter had the greatest diagnostic efficiency in diagnosing a high proportion of patients with esophageal varices. The diagnostic efficiency of the combined criterion expressed by the area under the ROC curve was 0.8803. Interpretation and Conclusions. Real-time ultrasonography, by evaluation of splenic longitudinal diameter and portal vein diameter, is an effective non-invasive technique able to classify correctly a large proportion of HCV/HIV co-infected hemophilic patients with esophageal varices.

High rate of human herpesvirus-8 seroprevalence in thalassemic patients in Italy.

BACKGROUND: The potential risk of acquiring infection by the novel human herpesvirus-8 (HHV-8) through blood derivatives is still debated. OBJECTIVES: In the present study, we determined HHV-8 seroprevalence in beta-thalassemic patients living in Italy. STUDY DESIGN: We have analysed 86 patients from Sardinia, an island characterised by a high diffusion of HHV-8, as well as 33 thalassemics from the area of Rome, where a lower rate of HHV-8 infection has been reported. These data have been compared with HHV-8 seroprevalence found in healthy controls living in the same areas of the assayed patients. RESULTS AND CONCLUSIONS: A three-fold increase in HHV-8 seroprevalence was found among thalassemic patients when compared to control groups taken from the same regions (17.6% versus 5.1%). This risk factor was statistically significant when considering the Sardinians alone (P = 0.01) and the entire population analysed in the present survey (P = 0.0006). In the Roman area also an increased seroprevalence in thalassemic subjects was found (12.1% versus 4.6%) but it was not statistically significant (P = 0.2). HHV-8 is sporadically present in the blood of healthy individuals and it is unknown whether the virus eventually present in donors' blood is completely cleared by the treatments which blood undergoes before red cells are transfused. Based on these considerations, we hypothesise that multiply transfused subjects living in areas at high HHV-8 prevalence present an increased risk of being infected.

Staphylococcus aureus bacteremia in patients with hematologic malignancies: a retrospective case-control study.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus bacteremia (SAB) continues to be a major problem related to both community and nosocomially acquired infection. Nevertheless few data are presently available in literature about this infection in patients with hematologic malignancies. DESIGN AND METHODS: The purpose of this retrospective study was to report further data on the clinical characteristics and outcome of patients with SAB. All episodes of SAB occurring between January 1997 and June 2001 were identified and defined by analysis of the patients' clinical records. RESULTS: The nosocomial mortality rate was only 3.5% and no patient developed secondary complications. Comparison between neutropenic hematologic patients with SAB and neutropenic hematologic patients with Gram-negative bacteremia (GNB) revealed an higher mortality in the latter group (p=0.03); furthermore, severe sepsis and septic shock were more frequent in patients with GNB (p<0.001). Comparison between neutropenic patients with hematologic malignancies and non-neutropenic ones with other underlying diseases revealed significantly higher morbidity and mortality rates in the latter group. Non neutropenic patients seemed to be more susceptible to both early complications, such as severe sepsis or septic shock (p=0.002) and to later ones, such as endocarditis and metastatic abscesses (p=0.02). INTERPRETATION AND CONCLUSIONS: Our results seem to suggest that SAB in patients with hematologic malignancies is often a low inoculum infection associated with negligible morbidity and mortality rates, especially when adequate antistaphylococcal therapy is administered promptly.

Mucormycosis in hematologic patients.

BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients affected by hematologic malignancies who developed mucormycosis and to ascertain the factors which influenced the outcome following mycotic infection. DESIGN AND METHODS: This was a retrospective study conducted over a 15-year period (1987-2001). The study included 59 patients with hematologic malignancies with a proven or probable mucormycosis admitted in 18 Hematology Divisions in tertiary care or university hospitals. RESULTS: The most frequent sites of infection were lung (64%) and orbito-sinus-facial (24%); cerebral involvement observed in 19% of cases was always associated with other sites of infection. Antifungal treatment was empirically administered in 49 patients (83%); 7 patients underwent radical surgical debridement (12%). Therapy was successful for only 18 patients (37%). Forty-seven patients died within 3 months of the diagnosis of fungal infection: the cause of death was mucormycosis in 41 patients (87%) and progression of hematologic disease in 6 patients (13%). At univariate analysis, the factors that correlated with a positive outcome from infection were the following: male sex, amphotericin B treatment, neutrophil recovery from post-chemotherapy aplasia. At multivariate analysis, the only factor that significantly correlated with recovery from infection was the liposomal amphotericin B treatment. INTERPRETATION AND CONCLUSIONS: Mucormycosis is a rare filamentous fungal infection that occurs most frequently in neutropenic patients with acute leukemia. It does not seem to have increased in recent years. Although a reduction of mortality has been observed recently, the mortality rate still remains high. Extensive and aggressive diagnostic and therapeutic procedures are essential in order to improve the prognosis in these patients.

Cryptococcosis in patients with hematologic malignancies. A report from GIMEMA-infection.

BACKGROUND AND OBJECTIVES: Cryptococcosis is an important cause of morbidity and death in immunocompromised patients. The aim of this study was to evaluate clinical and laboratory characteristics, and outcome of patients with cryptococcosis complicating hematologic diseases. DESIGN AND METHODS: This was a retrospective study, conducted over a ten-year period (1993-2002) in 21 hematology divisions, in tertiary care or university hospitals. RESULTS: This study evaluated 17 patients with hematologic diseases who developed cryptococcosis. Possible risk factors recognized before the onset of the infection were: administration of steroids for the underlying malignancy (6 patients), diabetes mellitus (4 patients), cutaneous lesions (2 patients) and autoimmune disease, hepatic cirrhosis, chronic renal failure and exposure to pigeons (1 patient each). Five patients received prophylaxis, consisting of fluconazole in 2 cases. Fever, neurological and respiratory signs developed according to the primary sites of infection (5 blood, 5 central nervous system, 4 lung, and 1 each in gut, skin and mouth). Diagnosis was made by positive microbiological culture, antigen detection in serum or cerebrospinal fluid, or polymerase chain reaction. All patients started specific treatment (fluconazole, 7 patients; amphotericin-B deoxycolate or liposomal amphotericin-B, 10 patients). Two patients died from cryptococcosis within 30 days after diagnosis. INTERPRETATION AND CONCLUSIONS: Cryptococcosis in patients with hematologic malignancies is a rare complication. In neutropenic patients, it is less fatal than other fungal infections (i.e. aspergillosis or candidemia). Specific treatment, started promptly, positively influences the outcome.