National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany - study protocol of a mixed-methods project.

BACKGROUND: In the SARS-CoV-2 pandemic, general and specialist Palliative Care (PC) plays an essential role in health care, contributing to symptom control, psycho-social support, and providing support in complex decision making. Numbers of COVID-19 related deaths have recently increased demanding more palliative care input. Also, the pandemic impacts on palliative care for non-COVID-19 patients. Strategies on the care for seriously ill and dying people in pandemic times are lacking. Therefore, the program 'Palliative care in Pandemics' (PallPan) aims to develop and consent a national pandemic plan for the care of seriously ill and dying adults and their informal carers in pandemics including (a) guidance for generalist and specialist palliative care of patients with and without SARS-CoV-2 infections on the micro, meso and macro level, (b) collection and development of information material for an online platform, and (c) identification of variables and research questions on palliative care in pandemics for the national pandemic cohort network (NAPKON). METHODS: Mixed-methods project including ten work packages conducting (online) surveys and qualitative interviews to explore and describe i) experiences and burden of patients (with/without SARS-CoV-2 infection) and their relatives, ii) experiences, challenges and potential solutions of health care professionals, stakeholders and decision makers during the SARS-CoV-2 pandemic. The work package results inform the development of a consensus-based guidance. In addition, best practice examples and relevant literature will be collected and variables for data collection identified. DISCUSSION: For a future "pandemic preparedness" national and international recommendations and concepts for the care of severely ill and dying people are necessary considering both generalist and specialist palliative care in the home care and inpatient setting.

Pitfalls in accelerometer-based measurement of physical activity: The presence of reactivity in an adult population.

When a behavior is monitored, it is likely to change, even if no change may be intended. This phenomenon is known as measurement reactivity. We investigated systematic changes in accelerometer-based measures over the days of monitoring as an indicator of measurement reactivity in an adult population. One hundred seventy-one participants from the general population (65% women; mean age = 55 years, range: 42-65 years) wore accelerometers for 7 consecutive days to measure sedentary behavior and physical activity (PA). Latent growth models were used (a) to investigate changes in accelerometer wear time over the measurement days and (b) to identify measurement reactivity indicated by systematic changes in sedentary time (ST), light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Over the measurement days, participants reduced accelerometer wear time by trend (rate of change [b] = -4.7 min/d, P = .051, Cohen's d = .38), increased ST (b = 2.4 min/d, P = .018, d = .39), and reduced LPA (b = -2.4 min/d, P = .015, d = .38). Participants did not significantly reduce MVPA (P = .537). Our data indicated that accelerometry might generate reactivity. Small effects on ST and LPA were found. Thus, the validity of accelerometer-based data on ST and LPA may be compromised. Systematic changes observed in accelerometer wear time may further bias accelerometer-based measures. MVPA seems to be less altered due to the presence of an accelerometer.

[Rehabilitation Processes in Out- and Inpatient Rehabilitation after Radical Prostatectomy]. / Rehabilitationsprozesse in ambulanter und stationärer Rehabilitation nach radikaler Prostatovesikulektomie.

We evaluated processes in in- and outpatient rehabilitation after radical prostatectomy. Overall, we analyzed motivation and expectations of 119 in- and 719 outpatients (aged≤64) at the beginning of rehabilitation as well as satisfaction and the amount of interventions at the end. Compared to inpatients outpatients had a higher socio-economic status and better physical condition. Both groups reported similar outcomes regarding motivation, expectation and satisfaction. Furthermore in- and outpatients got a comparable amount of interventions, but both groups differed to some extent in regard to the kind of interventions. In- and outpatients are comparable in regard to their received amount of interventions. Discrepancies concerning the kind of interventions are due to differences between in- and outpatients. The results indicate specific patients' characteristics in both settings, but more research is needed to verify these findings.

[Collaborative Goal Setting in Rehabilitation (ParZivar II): Evaluation of an Intervention in Patients with Chronic Back Pain]. / Partizipative Zielvereinbarung in der Rehabilitation (ParZivar II): Evaluation einer Intervention bei Patienten mit chronischen Rückenschmerzen.

OBJECTIVE: The "ParZivar II" project had 2 aims: optimization of the "ParZivar I" intervention by individual coaching of physicians, and evaluation of the optimized intervention. METHODS: The intervention was evaluated in a sequential control group design in 4 rehabilitation facilities with 3 measurement points. A total of n=279 patients with chronic low back pain participated in the study. RESULTS: The optimized intervention shows the potential to statistically significantly improve proximal outcomes (e. g. goal-centric processes or patient-physician interaction). Regarding distal outcomes, no statistically significant differences were found. CONCLUSION: The "ParZivar" intervention is a suitable approach to increase participative goal setting. Due to the complexity of the intervention, problems of dissemination and the potential for improvement in study design, there is a need for further research.

["Active in rehab": development and formative evaluation of a patient education program to increase health literacy of patients with chronic illness]. / "Aktiv in der Reha": Entwicklung und formative Evaluation einer Patientenschulung zur Förderung der Gesundheitskompetenz von chronisch Kranken.

OBJECTIVE: The aim of the article is to describe the development, the process of manualisation and results from the formative evaluation of a patient-oriented patient education program to increase health literacy of patients with chronic illness ("Active in rehab"). METHODS: Themes of the patient education program were extracted from 17 focus groups. An expert meeting was conducted to validate the content of the patient education program. The formative evaluation was based on a questionnaire (N(max) = 295 patients and N(max) = 39 trainers). RESULTS: The patient education program includes 4 modules with 3 themes (bio-psycho-social model, rehabilitation goals, communication competencies). The evaluation of the modules was good to very good. An analysis of free texts and a follow-up survey among trainers helped us to infer important improvements to the patient education program. CONCLUSION: RESULTS from the formative evaluation show that the patient education program meets patients and trainers needs and is accepted.

[Quality of vocational education in speech therapy - development and implementation of a quality assurance programme]. / Therapeutenausbildung auf dem Prüfstand - Entwicklung und Umsetzung eines Verfahrens zur Qualitätssicherung der logopädischen Ausbildung.

The provision of high-quality health-services is only possible if it is based on vocational education of corresponding quality. To promote the quality of vocational education in speech therapy, a quality assurance programme was developed in a scientifically supervised multi-step process. The main goals of the quality assurance programme include: (i) external review of the quality of education by means of well-defined criteria, (ii) certification of schools that meet the requirements, and (iii) provision of feedback to schools about their results. A total of 208 quality indicators cover the essential aspects of vocational education in speech therapy, and apply to the structural, process and outcome quality. These indicators are based on a literature survey as well as on expert opinion, and are calibrated by data. The data are collected by using questionnaires (school management, teachers in speech therapy, students, consecutive patient sample) and are validated by specific document analyses and telephone audits. Each school receives an individual quality report of its achieved results benchmarked to other schools. Since the initial implementation in 2008, a total of 50 schools participated in the quality assurance programme and 41 achieved certification. Therefore, the defined set of quality criteria has been disseminated and utilized by about half of all German schools for vocational education in speech therapy. The evaluation of the data on quality collected across all schools highlights the strengths and weaknesses of vocational education as well as the demands for quality improvement.

[Comprehensibility of patient education in orthopaedic rehabilitation: a qualitative study on patients and providers]. / Verständlichkeit von Patientenschulungen in der orthopädischen Rehabilitation: Qualitative Erhebung bei Rehabilitanden und Schulungsleitern.

STUDY OBJECTIVE: An important requirement for achieving postulated goals in the context of patient education is that patient education be conducted in a way that the patients can understand it. It is the objective of this explorative study to examine how patients and providers evaluate the comprehensibility and patients' comprehension of patient education under routine conditions during orthopaedic rehabilitation. Furthermore, we aim to explore the influencing factors that patients and providers describe as conducive and counterproductive to the comprehensibility of patient education, and the ideas or desires they have as to how patient education can be made more comprehensible. METHODS: We conducted guided focus groups with 50 patients with chronic back pain or osteoarthritis aged between 22 and 71 years (M=50.4, SD=9.4) and 35 patient education providers aged between 26 and 61 years (M=44.9, SD=9.8) in a total of 9 orthopaedic rehabilitation centres. Qualitative analyses of the interview transcripts were conducted according to Mayring's content analytic approach using Atlas.ti software. RESULTS: Patients and providers evaluate patient education as generally comprehensible. The involvement of patients in patient education is reported by both patients and providers as the main conducive factor. Patients describe poor (e. g. superficial or contradictory) information as counterproductive regarding comprehensibility, while providers tend to mention patients' lack of motivation and of taking personal responsibility as hindering patients' comprehension. Patients' and providers' proposals and ideas can be organized in the topics patient education (e. g. stronger reference to patients' everyday life), providers (e. g. improving providers' tutoring skills), information (e. g. more information), patient involvement (e. g. stronger consideration of patients' interests), organization (e. g. smaller groups), and goal clarification (e. g. consideration of patients' expectations). CONCLUSION: Our results reveal that good comprehensibility can be achieved in patient education during routine orthopaedic rehabilitation. They also show the factors that account for good comprehensibility. The counterproductive factors described by patients and providers provide evidence of the factors that may hold potential for improving patient education with regard to comprehensibility.

[Evaluation of a Vocationally Oriented Concept within Inpatient Oncological Rehabilitation]. / Evaluation eines berufsbezogenen Konzepts im Rahmen der stationären onkologischen Rehabilitation.

AIM OF THE STUDY: We evaluated an occupation-related rehabilitation program, which has been designed to enhance the return to work of cancer patients. As return to work plays an important role to get back to normalcy after suffering from cancer, there is a substantial need for support and evaluated programs. METHODS: The study had a quasi-experimental design with an intervention group (IG) and a comparison group (CG). We defined performance-related outcomes (e. g. return to work, self-assessed working capacity), asked patients if they needed further vocational advice and how helpful they estimated the rehabilitation treatment. 1 year after the end of rehabilitation 309 employed patients had completed the study (65%). We addressed our research questions using non-parametric tests, t-tests, analyses of variance and logistic regressions. RESULTS: Of the 309 patients 58% started rehabilitation not later than 14 days after the end of acute treatment while the other 42% had finished their treatments at least some weeks or even months ago. Patients of the IG evaluated the work-related rehabilitation offers significantly better and needed less additional vocational advice after the end of rehabilitation (n. s.). Regarding the patients, who started rehabilitation not later than 14 days after the end of acute treatment (beginning of rehabilitation n=269, 12 months after rehabilitation n=174), the IG achieved a slightly higher return-to-work-rate 12 months after the end of rehabilitation (81% IG, 76% CG, n. s.). Above that the IG estimated their subjective working capacity significantly more often as fully re-established (IG 46%; CG 29%, p=0,030). CONCLUSIONS: A high percentage of the patients return to work (78%). These results show the success of oncological rehabilitation in helping patients to return to work. In addition, the occupation-related rehabilitation program enhances subjective variables as the satisfaction of the patients regarding the information and the improvement of the patients' working-capacity.

[Female patients with fibromyalgia syndrome in somatic and psychosomatic rehabilitation center - an exploratory study on access routes and differences in patient characteristics]. / Fibromyalgiesyndrom-Patientinnen in psychosomatischen und somatischen Rehabilitationseinrichtungen - eine explorative Studie zu Zugangswegen und Unterschieden in Patientenmerkmalen.

STUDY OBJECTIVE: Fibromyalgia syndrome (FMS) is characterized by e. g. chronic, multilocular pain, and mental health problems. In Germany, patients with FMS are treated in somatic and psychosomatic rehabilitation centers - specialized for rheumatic diseases (somatic) or psychosomatic diseases. The aim of this study is to identify the status quo of FMS patients' access routes to the rehabilitation system, and to identify their predictors for being assigned to one or the other indication group. METHOD: Our cohort consists of 197 FMS patients from 3 psychosomatic (M=49.9 years) and 223 FMS patients (M=50.2 years) from 3 somatic rehabilitation centers. At the beginning of rehabilitation, patients filled out a questionnaire packet to identify their access routes to the rehabilitation centers and to record patients' disease-related, psychosocial and socio-demographic characteristics. To analyze the results we used descriptive calculations, calculated bivariate correlations, and conducted binary logistic regression analysis for the prediction of group membership. RESULTS: The access routes of FMS patients to a somatic or a psychosomatic rehabilitation center were often similar. Some items revealed significant group differences, i. e., a higher primary -rejection rate, longer waiting period between application for rehabilitation and its approval, and between the application itself and initiation of psychosomatic rehabilitation in comparison to somatic FMS patients. Prior experience of out-patient psychotherapy, and expectations ("psychological support") for the rehabilitation were predictive patient characteristics for the assignment into a psychosomatic rehabilitation center. Marriage, motivation, and expectations ("physical improvement" and "interaction with other patients") for the rehabilitation were predictive patient characteristics for the assignment in a somatic rehabilitation center. The predictors clarified 32% of the variance of group membership. CONCLUSION: Our results provide initial evidence of how FMS patients access the German rehabilitation system and which of their characteristics are responsible for being assigned to a particular rehabilitation setting.

Symptom burden, psychosocial distress and palliative care needs in heart failure - A cross-sectional explorative pilot study.

BACKGROUND: Beyond guideline-directed treatments aimed at improving cardiac function and prognosis in heart failure (HF), patient-reported outcomes have gained attention. PURPOSE: Using a cross-sectional approach, we assessed symptom burden, psychosocial distress, and potential palliative care (PC) needs in patients with advanced stages of HF. METHODS: At a large tertiary care center, we enrolled HF patients in an exploratory pilot study. Symptom burden and psychosocial distress were assessed using the MIDOS (Minimal Documentation System for Patients in PC) questionnaire and the Distress Thermometer (DT), respectively. The 4-item Patient Health Questionnaire (PHQ-4) was used to screen for anxiety and depression. To assess PC needs, physicians used the "Palliative Care Screening Tool for HF Patients". RESULTS: We included 259 patients, of whom 137 (53%) were enrolled at the Heart Failure Unit (HFU), and 122 (47%) at the outpatient clinic (OC). Mean age was 63 years, 72% were male. New York Heart Association class III or IV symptoms were present in 56%. With a mean 5-year survival 64% (HFU) vs. 69% (OC) calculated by the Seattle Heart Failure Model, estimated prognosis was comparatively good. Symptom burden (MIDOS score 8.0 vs. 5.4, max. 30 points, p < 0.001) and level of distress (DT score 6.0 vs. 4.8, max. 10 points, p < 0.001) were higher in hospitalised patients. Clinically relevant distress was detected in the majority of patients (HFU 76% vs. OC 57%, p = 0.001), and more than one third exhibited at least mild symptoms of depression or anxiety. Screening for PC needs revealed 82% of in- and 52% of outpatients fulfil criteria for specialized palliative support. CONCLUSION: Despite a good prognosis, we found multiple undetected and unaddressed needs in an advanced HF cohort. This study's tools and screening results may help to early explore these needs, to further improve integrated HF care.

[Restrictions in participation in women with fibromyalgia syndrome. An explorative pilot study]. / Beeinträchtigungen der Teilhabe bei Patientinnen mit Fibromyalgiesyndrom. Eine explorative Pilotstudie.

BACKGROUND: Patients with fibromyalgia syndrome are often severely restricted in their ability to participate in everyday activities and in social interaction. The aim of this study was to document female patients' subjectively-perceived limitations in participation and to develop material to generate items for a specific participation questionnaire. MATERIAL AND METHODS: We collected data from 8 groups of women with fibromyalgia syndrome (n=38), and developed a hierarchical system of categories using the patients' statements (ATLAS.ti; Qualitative Data Analysis). RESULTS: Our final group of categories contains 10 superordinate categories. Women with fibromyalgia syndrome often describe restrictions in their relationships with other people, and the impaired ability to engage in social and leisure activities. They speak of difficulties at the workplace, while doing housework, and complain about a lack of understanding and awareness on the part of the general public. CONCLUSION: Fibromyalgia syndrome patients admit to be extremely impaired in a variety of social roles. Their statements have enabled us to develop a questionnaire that reflects the range of factors restricting participation from the patient's perspective.

[Gender-related aspects of returning to work in cancer survivors. A systematic review]. / Geschlechtsspezifische Aspekte der Rückkehr zur Arbeit bei Patientinnen und Patienten mit einer Krebserkrankung. Ein systematisches Review.

Due to improved prognosis most cancer survivors are nowadays able to return to work. This review explored gender-related differences in work-related outcomes after cancer. A systematic search of studies on work-related issues in cancer survivors published between January 2001 and July 2011 was conducted. 44 original publications met the inclusion criteria (adult cancer survivors, focus on work-related outcomes, gender-specific report of results). The results of these studies indicate that impaired work ability is more common among female cancer survivors than among male cancer survivors as well as the reduction of working hours and income losses. Supportive work environments seem to be particularly helpful for the successful and long-lasting re-integration of female survivors. More systematic research and separate analyses for women and men are needed to fully comprehend gender differences in work-related outcomes. Broader knowledge can then be helpful in creating gender-specific return-to-work interventions.

Fluorite-related iridate Pr3IrO7: crystal growth, structure, magnetism, thermodynamic, and optical properties.

Spin-orbit coupling in heavy 5dmetal oxides, in particular, iridates have received tremendous interest in recent years due to the realization of exotic electronic and magnetic phases. Here, we report the synthesis, structural, magnetic, thermodynamic, and optical properties of the ternary iridate Pr3IrO7. Single crystals of Pr3IrO7have been grown by the KF flux method. Structural analysis shows that Pr3IrO7crystallizes in an orthorhombic phase withCmcmsymmetry. The electron energy loss spectroscopy study indicates that Pr is in a 3+ valence state, which implies a 5+ oxidation state of Ir. Magnetization data measured at high and low magnetic fields do not exhibit any bifurcation betweenMZFCandMFC, however, a weak hump inM(T) is observed atT∗∼10.4 K. The specific heat data reveal two maxima at ∼253 and ∼4.8 K. The optical conductivityσ1(ω)spectrum shows 24 infrared-active phonon modes and reveals an insulating behavior with an optical gapΔOPof size ∼500 meV. During cooling down, the temperature-dependent reflectivity spectrum reveals eight extra phonon modes below the structural phase transition (∼253 K). An anomaly is observed at aroundT∗in the temperature evolution of infrared-active mode frequencies suggesting the presence of significant spin-phonon coupling in the system.

Epidermal growth factor receptors: critical mediators of multiple receptor pathways.

Recently, the receptor for epidermal growth factor (EGF) was identified as a downstream element in different signaling pathways. This expanded its classical function as a receptor for EGF-like ligands to a role as mediator of diverse signaling systems and as a switch point of a cellular communication network. In addition, several downstream targets, (e.g. Smad proteins and STATs) into which signals from synergistic and antagonistic signaling pathways converge, were identified.

Molecular targets for breast cancer therapy and prevention.

The recent completion of the human genome sequence has raised great hopes for the discovery of new breast cancer therapies based on newly-discovered genes linked to breast cancer development and progression. Here we describe breast cancer therapies that have emerged from gene-based scientific efforts over the past 20 years and that are now approved for clinical testing or treatment.

Global cancer incidence and mortality caused by behavior and infection.

OBJECTIVE: The objective is to systematically estimate the current cancer incidence and mortality from the six leading cancer types globally and by sub-regions resulting from exposure to known risk factors such as tobacco use, elevated body weight, alcohol consumption, inadequate physical activity, unhealthy diet and infections. METHODS: Cancer incidence, mortality and burden of disease caused by the main cancer risk factors were calculated using comparative risk assessment methods and updated data on mortality and risks. RESULTS: Lung cancer was the most common cancer in men and breast cancer the most common cancer in women, both in terms of incidence and mortality. The five leading behavioral and dietary risks--high body mass index, low fruit and vegetable intake, physical inactivity, tobacco use and alcohol use--were responsible for 24% of new cancer cases and 30% of cancer deaths. Cancers with the largest proportions attributable to preventable risk factors were cervical cancer (100%) and lung cancer (71%). Seventy percent of liver cancers and 60% of stomach cancers were due to infectious agents. A higher proportion of cancer deaths was attributed to infections in low- and middle-income than in high-income countries. CONCLUSIONS: The cancer burden is driven by changes in exposure to influential risk factors and can be influenced by preventive interventions aimed at reducing these exposures.

A pre-registered short-term forecasting study of COVID-19 in Germany and Poland during the second wave.

Disease modelling has had considerable policy impact during the ongoing COVID-19 pandemic, and it is increasingly acknowledged that combining multiple models can improve the reliability of outputs. Here we report insights from ten weeks of collaborative short-term forecasting of COVID-19 in Germany and Poland (12 October-19 December 2020). The study period covers the onset of the second wave in both countries, with tightening non-pharmaceutical interventions (NPIs) and subsequently a decay (Poland) or plateau and renewed increase (Germany) in reported cases. Thirteen independent teams provided probabilistic real-time forecasts of COVID-19 cases and deaths. These were reported for lead times of one to four weeks, with evaluation focused on one- and two-week horizons, which are less affected by changing NPIs. Heterogeneity between forecasts was considerable both in terms of point predictions and forecast spread. Ensemble forecasts showed good relative performance, in particular in terms of coverage, but did not clearly dominate single-model predictions. The study was preregistered and will be followed up in future phases of the pandemic.

Kinetics of binding, endocytosis, and recycling of EGF receptor mutants.

This report describes analysis of factors which regulate the binding of EGF to EGF receptor, receptor internalization, and receptor recycling. Three different methods were used to inhibit high-affinity EGF binding as measured at equilibrium: treatment of cells with an active phorbol ester (PMA), binding of a mAb directed against the EGF receptor (mAb108), and truncation of most of the cytoplasmic domain of the receptor. These treatments reduced the rate at which low concentrations of EGF bound to cells, but did not affect the rate of EGF dissociation. We conclude that high-affinity EGF binding on living cells results from a difference in the apparent on rate of EGF binding. We then used these conditions and cell lines to test for the rate of EGF internalization at different concentrations of EGF. We demonstrate that internalization of the EGF receptor is stimulated roughly 50-fold at saturating concentrations of EGF, but is stimulated an additional two- to threefold at low concentrations (less than 1 nM). Four treatments reduce the rate of internalization of low concentrations of EGF to the rate seen at saturating EGF concentrations. Phorbol ester treatment and mAb108 binding to "wild type" receptor reduce this rate (and reduce high-affinity binding). Point mutation at Lys721 (kinase negative EGF receptor) and point mutation at Thr654 (removing a major site of protein kinase C phosphorylation) reduce the internalization rate, without affecting high-affinity binding. We suggest that while EGF stimulates endocytosis for all receptors, high-affinity receptors bind and are internalized more quickly than low-affinity receptors. Tyrosine kinase activity and the Thr654 region appear necessary for this response.

Separate endocytic pathways of kinase-defective and -active EGF receptor mutants expressed in same cells.

Ligand binding to the membrane receptor for EGF induces its clustering and internalization. Both receptor and ligand are then degraded by lysosomal enzymes. A kinase defective point mutant (K721A) of EGF receptor undergoes internalization similarly to the wild-type receptor. However, while internalized EGF molecules bound to either the wild-type or mutant receptors are degraded, the K721A mutant receptor molecules recycle to the cell surface for reutilization. To investigate the mechanism of receptor trafficking, we have established transfected NIH-3T3 cells coexpressing the kinase-negative mutant (K721A) together with a mutant EGF receptor (CD63) with active kinase. CD63 was chosen because it behaves like wild-type EGF receptor with respect to biological responsiveness and cellular routing but afforded immunological distinction between kinase active and inactive mutants. Although expressed in the same cells, the two receptor mutants followed their separate endocytic itineraries. Like wild-type receptor, the CD63 mutant was downregulated and degraded in response to EFG while the kinase-negative mutant K721A returned to the cell surface for reutilization. Intracellular trafficking of EGF receptor must be determined by a sorting mechanism that specifically recognizes EGF receptor molecules according to their intrinsic kinase activity.

Annexin I is phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor.

We have previously shown that an active epidermal growth factor receptor (EGF-R) kinase is necessary for efficient sorting of the EGF-R to the lysosome, and we have shown that this occurs in the multivesicular body (MVB), where EGF-R are sorted away from recycling receptors by being removed to the internal vesicles of the MVB. The aim of the present study was to identify substrates of the EGF-R kinase associated with MVBs which might play a role in this sorting process. We used a density shift technique to isolate MVBs and show that the major substrates phosphorylated in vitro within MVBs which contain an active EGF-R kinase are the EGF-R itself and annexin I. Annexin I is associated with both plasma membrane and MVBs in a calcium-independent manner but can be phosphorylated in vitro only in MVBs. Phosphorylation of calcium-independent annexin I in isolated MVBs converts it to a form that requires calcium for membrane association. In cells with an active EGF-R kinase the amount of calcium-independent annexin I in MVBs is reduced, suggesting that a phosphorylation-induced conversion of the calcium independent to the calcium-dependent form also occurs in vivo. Our observations, together with the known properties of annexin I in mediating membrane fusion, suggest that inward vesiculation in MVBs is induced by the EGF-R and is mediated by phosphorylated annexin I.