Youth Perspectives on the Effects of a Family-centered Media Literacy Intervention to Encourage Healthier Eating.

A pretest-posttest field test with control group (N = 189 parent-child dyads) tested a structural model representing youths' (ages 9-14) perspectives to examine the efficacy of a family-centered, media literacy-oriented intervention promoting fruit and vegetable consumption. The intervention facilitated critical discussion about nutrition and media, mentored by the parent. Results showed that youths' increases in fruit and vegetable consumption flowed from parent-child discussion of nutrition labels, which was predicted by child-initiated discussion, critical thinking about media sources, and critical thinking about media content. Multivariate analyses revealed that the intervention was productive for all participating age groups and for all dependent variables. The results suggest that a developmental progression from critical thinking about source to critical thinking about content affects behavior change and can be catalyzed through media literacy education and encouragement to discuss media messages (i.e. practice) with parents.

Effects of Family-Centered Media Literacy Training on Family Nutrition Outcomes.

Parents frustrated about food marketing influences need media management skills to challenge marketing messages and interpret factual content. We tested a media literacy-based, family-centered intervention to reduce effects of appealing, but unrealistic, food marketing. We hypothesized that participation would facilitate family discussion that improves the home dietary environment and increases youth consumption of fruits and vegetables. Parent-child (age 9-14) dyads (N = 189) participated in a matched-group, pretest/posttest field experiment testing a 6-week media literacy-based curriculum. Hypothesis testing employed multiple analysis of covariance and Bayesian multigroup structural equation modeling (MGSEM). Improved nutrition outcomes for parents included talk with youth about food nutrition labels (d = 0.343) and ratio of healthy to unhealthy food in home (d = 0.232); youth improved talk with parent about food nutrition labels (d = 0.211), vegetables eaten yesterday (d = 0.264), and fruit eaten yesterday (d = 1.386). Bayesian MGSEM revealed that in the intervention group, 12 of 17 tested paths were significant (p < .05), compared with only 4 in the control group, with average effect size magnitudes of 0.236 and 0.113, respectively. Media literacy education can empower parents and improve youths' critical thinking to reduce negative effects of food marketing on families and improve use of media to obtain nutrition information that aids dietary choices. This approach reduces the risk for reactance from youth who like media and resist limiting media use, while helping families use media together to make better nutrition decisions.

Clash of the Primary Motivations: Motivated Processing of Emotionally Experienced Content in Fear Appeals About Obesity Prevention.

This study examined individuals' physiological and cognitive responses to different types of emotionally experienced content located in obesity prevention fear appeals. Results suggested that experienced valence impacted individuals' attention and memory as a function of experienced arousal level. Local content that created coactive highly arousing experiences received the most attention, though visual recognition suggested these messages were more difficult to encode. Local content that created negative moderately arousing experiences was best encoded. Global message evaluation data suggest that moderately arousing messages with a change in experienced valence may prove to be most effective, as they ensure attention and good memory while keeping high self-reported interest, and a high level of perceived severity of obesity. Implications and suggestions for future research are discussed.

Atezolizumab in platinum-treated locally advanced or metastatic urothelial carcinoma: post-progression outcomes from the phase II IMvigor210 study.

BACKGROUND: Conventional criteria for tumor progression may not fully reflect the clinical benefit of immunotherapy or appropriately guide treatment decisions. The phase II IMvigor210 study demonstrated the efficacy and safety of atezolizumab, a programmed death-ligand 1-directed antibody, in patients with platinum-treated locally advanced or metastatic urothelial carcinoma. Patients could continue atezolizumab beyond Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 progression at the investigator's discretion: this analysis assessed post-progression outcomes in these patients. PATIENTS AND METHODS: Patients were treated with atezolizumab 1200 mg i.v. every 3 weeks until loss of clinical benefit. Efficacy and safety outcomes in patients who experienced RECIST v1.1 progression and did, or did not, continue atezolizumab were analyzed descriptively. RESULTS: In total, 220 patients who experienced progression from the overall cohort (n = 310) were analyzed: 137 continued atezolizumab for ≥ 1 dose after progression, 19 received other systemic therapy, and 64 received no further systemic therapy. Compared with those who discontinued, patients continuing atezolizumab beyond progression were more likely to have had a baseline Eastern Cooperative Oncology Group performance status of 0 (43.1% versus 31.3%), less likely to have had baseline liver metastases (27.0% versus 41.0%), and more likely to have had an initial response to atezolizumab (responses in 11.7% versus 1.2%). Five patients (3.6%) continuing atezolizumab after progression had subsequent responses compared with baseline measurements. Median post-progression overall survival was 8.6 months in patients continuing atezolizumab, 6.8 months in those receiving another treatment, and 1.2 months in those receiving no further treatment. Atezolizumab exposure-adjusted adverse event frequencies were generally similar before and following progression. CONCLUSION: In this single-arm study, patients who continued atezolizumab beyond RECIST v1.1 progression derived prolonged clinical benefit without additional safety signals. Identification of patients most likely to benefit from atezolizumab beyond progression remains an important challenge in the management of metastatic urothelial carcinoma. CLINICALTRIALS.GOV ID: NCT02108652.

Plasmonic modulator with >170 GHz bandwidth demonstrated at 100 GBd NRZ.

We demonstrate a plasmonic Mach-Zehnder (MZ) modulator with a flat frequency response exceeding 170 GHz. The modulator comprises two phase modulators exploiting the Pockels effect of an organic electro-optic material in plasmonic slot waveguides. We further show modulation at 100 GBd NRZ and 60 GBd PAM-4. The electrical drive signals were generated using a 100 GSa/s digital to analog converter (DAC). The high-speed and small-scale devices are relevant for next-generation optical interconnects.

Aspiration and dysphagia screening in acute stroke - the Gugging Swallowing Screen revisited.

BACKGROUND AND PURPOSE: The Gugging Swallowing Screen (GUSS) is a tool to screen aspiration risk in acute stroke. We aimed to replicate its validity in a larger second cohort of patients with acute stroke, including the more severe with a National Institutes of Health Stroke Scale (NIHSS) ≥ 15. METHODS: In a prospective, double-blind design, the GUSS was validated with the Fiberoptic Endoscopic Evaluation of Swallowing scale. Patients were categorized into different stroke severities as assessed by the NIHSS, and the diagnostic properties were calculated separately for each subgroup. RESULTS: A total of 100 patients with acute stroke were evaluated consecutively at a mean 1.7 ± 2.2 days after stroke. With the GUSS cut-off value of 14 points, the GUSS screened aspiration risk with a 96.5% sensitivity and 55.8% specificity (area under the curve, 0.76; 95% CI, 0.67-0.84), which corresponded well with the original publication. In the NIHSS < 5 group, the sensitivity and specificity levels were 71.4% and 88.8%, respectively. In the NIHSS ≥ 15 group, these levels changed to 100% and 20%, respectively. The high failure rate in completing the first part of the GUSS in the latter group was related to the low specificity. Diet recommendations following the GUSS were more conservative than those after Fiberoptic Endoscopic Evaluation of Swallowing. In particular, the GUSS overestimated the need for nasogastric tube feeding. CONCLUSIONS: This is the first time that a swallowing screening tool for patients with acute stroke has been revalidated in a larger population from another stroke center. The validity of a swallow screening test may vary according to different stroke severities.

(18) F-FDG PET/CT for initial staging in breast cancer patients - Is there a relevant impact on treatment planning compared to conventional staging modalities?

OBJECTIVE: To evaluate the impact of whole-body (18) F-FDG PET/CT on initial staging of breast cancer in comparison to conventional staging modalities. METHODS: This study included 102 breast cancer patients, 101 patients were eligible for evaluation. Preoperative whole-body staging with PET/CT was performed in patients with clinical stage ≥ T2 tumours or positive local lymph nodes (n = 91). Postoperative PET/CT was performed in patients without these criteria but positive sentinel lymph node biopsy (n = 10). All patients underwent PET/CT and a conventional staging algorithm, which included bone scan, chest X-ray and abdominal ultrasound. PET/CT findings were compared to conventional staging and the impact on therapeutic management was evaluated. RESULTS: PET/CT led to an upgrade of the N or M stage in overall 19 patients (19 %) and newly identified manifestation of breast cancer in two patients (2 %). PET/CT findings caused a change in treatment of 11 patients (11 %). This is within the range of recent studies, all applying conventional inclusion criteria based on the initial T and N status. CONCLUSIONS: PET/CT has a relevant impact on initial staging and treatment of breast cancer when compared to conventional modalities. Further studies should assess inclusion criteria beyond the conventional T and N status, e.g. tumour grading and receptor status. KEY POINTS: • PET/CT may be relevant in staging breast cancer patients at higher risk for metastases • PET/CT may modify the N and M stage in multiple patients • PET/CT may impact treatment planning in breast cancer patients.

[Value of galactography for the diagnostic work-up of pathological nipple discharge in multimodal breast diagnostics. Part 2: a systematic review of the literature]. / Stellenwert der Galaktographie zur Abklärung pathologischer Sekretion in der komplementären Mammadiagnostik. Teil 2: Eine systematische Literaturanalyse.

BACKGROUND: The survey results of a previous study showed that galactography is now rarely used in Germany and newer methods are applied. The evidential value of galactography should be established and opposed to the evidential value of ultrasound (US) and magnetic resonance mammography (MRM). MATERIALS AND METHODS: A search was carried out in PubMed and Cochrane involving studies written in English or German. The level of evidence was measured according to the Oxford Centre for Evidence-based Medicine. RESULTS: A total of 19 studies were included, 14 with results on galactography, 10 on US and 5 on MRM. Almost all studies were retrospective with an evidence assigned to level 3b or lower. The results on the diagnostic values showed a very wide range. Because of very variable numbers of cases and consideration of various pathologies, the studies are only comparable to a limited extent. CONCLUSION: Galactography, US and MRM all show a weak level of evidence and no superiority of a particular method can be derived. Therefore, galactography can no longer be considered as a mandatory standard in modern multimodal imaging of the breast. Recommendations for the diagnostic work-up of pathological nipple discharge have to be included in current guidelines and must consider these facts.

T-DOpE probes reveal sensitivity of hippocampal oscillations to cannabinoids in behaving mice.

Understanding the neural basis of behavior requires monitoring and manipulating combinations of physiological elements and their interactions in behaving animals. We developed a thermal tapering process enabling fabrication of low-cost, flexible probes combining ultrafine features: dense electrodes, optical waveguides, and microfluidic channels. Furthermore, we developed a semi-automated backend connection allowing scalable assembly. We demonstrate T-DOpE (Tapered Drug delivery, Optical stimulation, and Electrophysiology) probes achieve in single neuron-scale devices (1) high-fidelity electrophysiological recording (2) focal drug delivery and (3) optical stimulation. The device tip can be miniaturized (as small as 50 µm) to minimize tissue damage while the ~20 times larger backend allows for industrial-scale connectorization. T-DOpE probes implanted in mouse hippocampus revealed canonical neuronal activity at the level of local field potentials (LFP) and neural spiking. Taking advantage of the triple-functionality of these probes, we monitored LFP while manipulating cannabinoid receptors (CB1R; microfluidic agonist delivery) and CA1 neuronal activity (optogenetics). Focal infusion of CB1R agonist downregulated theta and sharp wave-ripple oscillations (SPW-Rs). Furthermore, we found that CB1R activation reduces sharp wave-ripples by impairing the innate SPW-R-generating ability of the CA1 circuit.

Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations dynamically coupled with hippocampal rhythms across brain states.

The granular retrosplenial cortex (gRSC) exhibits high-frequency oscillations (HFOs; ∼150 Hz), which can be driven by a hippocampus-subiculum pathway. How the cellular-synaptic and laminar organization of gRSC facilitates HFOs is unknown. Here, we probe gRSC HFO generation and coupling with hippocampal rhythms using focal optogenetics and silicon-probe recordings in behaving mice. ChR2-mediated excitation of CaMKII-expressing cells in L2/3 or L5 induces HFOs, but spontaneous HFOs are found only in L2/3, where HFO power is highest. HFOs couple to CA1 sharp wave-ripples (SPW-Rs) during rest and the descending phase of theta. gRSC HFO current sources and sinks are the same for events during both SPW-Rs and theta oscillations. Independent component analysis shows that high gamma (50-100 Hz) in CA1 stratum lacunosum moleculare is comodulated with HFO power. HFOs may thus facilitate interregional communication of a multisynaptic loop between the gRSC, hippocampus, and medial entorhinal cortex during distinct brain and behavioral states.

Performance evaluation of a new fourth-generation HIV combination antigen-antibody assay.

Education and diagnostic tests capable of early detection represent our most effective means of preventing transmission of human immunodeficiency virus (HIV). The importance of early detection is underlined by studies demonstrating increased life expectancy following early initiation of antiviral treatment. The Elecsys(®) HIV combi PT assay is a fourth-generation antigen-antibody combination assay developed to allow earlier detection of seroconversion, and to have increased sensitivity and improved specificity. We aimed to determine how early the assay could detect infection compared with existing assays; whether all HIV variants could be detected; and the assay's specificity using samples from blood donors, routine specimens, and patients with potential cross-reacting factors. Samples were identified as positive by the Elecsys(®) assay 4.9 days after a positive polymerase chain reaction result (as determined by the panel supplier), which was earlier than the 5.3-7.1 days observed with comparators. The analytical sensitivity of the Elecsys(®) HIV combi PT assay for the HIV-1 p24 antigen was 1.05 IU/mL, which compares favorably with the comparator assays. In addition, the Elecsys(®) assay identified all screened HIV subtypes and displayed greater sensitivity to HIV-2 homologous antigen and antibodies to HIV-1 E and O and HIV-2 than the other assays. Overall, the specificity of the Elecsys(®) assay was 99.88 % using samples from blood donors and 99.81 % when analyzing unselected samples. Potential cross-reacting factors did not interfere with assay performance. The Elecsys(®) HIV combi PT assay is a sensitive and specific assay that has been granted the CE mark according to Directive 2009/886/EC.

Direct search for a ferromagnetic phase in a heavily overdoped nonsuperconducting copper oxide.

The doping of charge carriers into the CuO(2) planes of copper oxide Mott insulators causes a gradual destruction of antiferromagnetism and the emergence of high-temperature superconductivity. Optimal superconductivity is achieved at a doping concentration p beyond which further increases in doping cause a weakening and eventual disappearance of superconductivity. A potential explanation for this demise is that ferromagnetic fluctuations compete with superconductivity in the overdoped regime. In this case, a ferromagnetic phase at very low temperatures is predicted to exist beyond the doping concentration at which superconductivity disappears. Here we report on a direct examination of this scenario in overdoped La(2-x)Sr(x)CuO(4) using the technique of muon spin relaxation. We detect the onset of static magnetic moments of electronic origin at low temperature in the heavily overdoped nonsuperconducting region. However, the magnetism does not exist in a commensurate long-range ordered state. Instead it appears as a dilute concentration of static magnetic moments. This finding places severe restrictions on the form of ferromagnetism that may exist in the overdoped regime. Although an extrinsic impurity cannot be absolutely ruled out as the source of the magnetism that does occur, the results presented here lend support to electronic band calculations that predict the occurrence of weak localized ferromagnetism at high doping.

[Value of galactography for the diagnostic work-up of pathological nipple discharge in multimodal breast diagnostics : Part 1: An online survey among German breast care centers.] / Stellenwert der Galaktographie zur Abklärung pathologischer Sekretion in der komplementären Mammadiagnostik : Teil 1: Eine Onlineumfrage an den deutschen Brustzentren.

PURPOSE: Galactography has been used in cases of pathological discharge for decades. Meanwhile other methods, such as high-resolution ultrasound (US) and magnetic resonance mammography (MRM) have been established for modern multimodal breast imaging. A survey among certified German breast care centers aimed to investigate to what extent galactography is currently used and whether newer techniques in multimodal imaging are preferred. MATERIALS AND METHODS: An anonymous online survey was carried out nationwide and open to 342 radiology units in certified German breast care centers. RESULTS: A total of 177 units (52 %) participated in the survey of which 13 % generally do not provide galactography, 33 % conduct a maximum of 5 galactographies per year, 24 % conduct 6-10, 18 % 11-20, 8 % 21-50 and 5 % 51-100. Of the participants 53 % give first priority to US and prefer galactography to MRM in stepwise diagnosis and 32 % prefer MRM to galactography. Only 4 % use galactography initially. CONCLUSION: Currently galactography is no longer a mandatory standard and newer methods are preferred. The evidential value of galactography in comparison to other techniques should be established on the basis of the literature. The second part of this paper will deal with this question.

Granular retrosplenial cortex layer 2/3 generates high-frequency oscillations coupled with hippocampal theta and gamma in online states or sharp-wave ripples in offline states.

Neuronal oscillations support information transfer by temporally aligning the activity of anatomically distributed 'writer' and 'reader' cell assemblies. High-frequency oscillations (HFOs) such as hippocampal CA1 sharp-wave ripples (SWRs; 100-250 Hz) are sufficiently fast to initiate synaptic plasticity between assemblies and are required for memory consolidation. HFOs are observed in parietal and midline cortices including granular retrosplenial cortex (gRSC). In 'offline' brain states (e.g. quiet wakefulness) gRSC HFOs co-occur with CA1 SWRs, while in 'online' states (e.g. ambulation) HFOs persist with the emergence of theta oscillations. The mechanisms of gRSC HFO oscillations, specifically whether the gRSC can intrinsically generate HFOs, and which layers support HFOs across states, remain unclear. We addressed these issues in behaving mice using optogenetic excitation in individual layers of the gRSC and high density silicon-probe recordings across gRSC layers and hippocampus CA1. Optogenetically induced HFOs (iHFOs) could be elicited by depolarizing excitatory neurons with 100 ms half-sine wave pulses in layer 2/3 (L2/3) or layer 5 (L5) though L5 iHFOs were of lower power than in L2/3. Critically, spontaneous HFOs were only observed in L2/3 and never in L5. Intra-laminar monosynaptic connectivity between excitatory and inhibitory neurons was similar across layers, suggesting other factors restrict HFOs to L2/3. To compare HFOs in online versus offline states we analyzed, separately, HFOs that did or did not co-occur with CA1 SWRs. Using current-source density analysis we found uniform synaptic inputs to L2/3 during all gRSC HFOs, suggesting layer-specific inputs may dictate the localization of HFOs to L2/3. HFOs occurring without SWRs were aligned with the descending phase of both gRSC and CA1 theta oscillations and were coherent with CA1 high frequency gamma oscillations (50-80 Hz). These results demonstrate that gRSC can internally generate HFOs without rhythmic inputs and that HFOs occur exclusively in L2/3, coupled to distinct hippocampal oscillations in online versus offline states.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial.

OBJECTIVE: To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). DESIGN: In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. RESULTS: Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. CONCLUSION: In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

Nanoplasma dynamics of single large xenon clusters irradiated with superintense x-ray pulses from the linac coherent light source free-electron laser.

The plasma dynamics of single mesoscopic Xe particles irradiated with intense femtosecond x-ray pulses exceeding 10(16) W/cm2 from the Linac Coherent Light Source free-electron laser are investigated. Simultaneous recording of diffraction patterns and ion spectra allows eliminating the influence of the laser focal volume intensity and particle size distribution. The data show that for clusters illuminated with intense x-ray pulses, highly charged ionization fragments in a narrow distribution are created and that the nanoplasma recombination is efficiently suppressed.

Intrarenal resistance index as a prognostic parameter in patients with liver cirrhosis compared with other hepatic scoring systems.

BACKGROUND AND AIMS: Patients with advanced liver cirrhosis who develop renal dysfunction have a poor prognosis. Elevated intrarenal resistance indices (RIs) due to renal vascular constriction have been described before in cirrhotic patients. In the current study, we prospectively investigated the course of intrarenal RIs and compared their prognostic impact with those of the Model for End-Stage Liver Disease (MELD) and the Child-Pugh scores. METHODS: Sixty-three patients with liver cirrhosis underwent a baseline visit which included a sonographic examination and laboratory tests. Forty-four patients were prospectively monitored. The end points were death or survival at the day of the follow-up visit. RESULTS: In 28 patients, a follow-up visit was performed after 22 ± 8 months (group 1). Sixteen patients died during follow-up after 12 ± 8 months (group 2). Group 2 patients showed a significantly higher baseline RI (0.76 ± 0.05) than group 1 patients (RI = 0.72 ± 0.06; p < 0.05). As shown by receiver operating characteristic analysis, the RI and the MELD score achieved similar sensitivity and specificity [area under the curve (AUC): 0.722; 95% confidence interval (95% CI): 0.575-0.873 vs. AUC: 0.724; 95% CI: 0.575-0.873, z = 0.029, n.s.] in predicting survival and were superior to the Child-Pugh score (AUC: 0.677; 96% CI: 0.518-0.837). CONCLUSION: The RI is not inferior in sensitivity and specificity to the MELD score. Cirrhotic patients with elevated RIs have impaired short- and long-term survival. The RI may help identify high-risk patients that require special therapeutic care.

Ventricular assist devices in acute heart failure.

In Western countries, the incidence of acute heart failure has been growing rapidly and is associated with increased incidence of mortality. Acute heart failure encompasses an extended spectrum of clinical presentation. From these, cardiogenic shock remains its most dramatic entity and is burdened by a dismal prognosis. As the initial therapeutic armamentarium (pressor agents, non-invasive or invasive ventilation using positive end-expiratory pressure, treatment of the damaging agent, ultrafiltration and intra-aortic balloon counterpulsation) might be soon overcome, implantation of mechanical ventricular assistance should be considered. Constant technical improvements have allowed quick and percutaneous implantation of such left ventricular assistance devices (LVADs). Herein, we review the technical characteristics and clinical data of the percutaneous LVADs currently available in Europe for treatment of overt cardiogenic shock.

Magnetism and disorder effects on muon spin rotation measurements of the magnetic penetration depth in iron-arsenic superconductors.

It is shown that attempts to accurately deduce the magnetic penetration depth λ of overdoped BaFe(1.82)Co(0.18)As2 single crystals by transverse-field muon spin rotation (TF µSR) are thwarted by field-induced magnetic order and strong vortex-lattice disorder. We explain how substantial deviations from the magnetic field distribution of a nearly perfect vortex lattice by one or both of these factors is also significant for other iron-arsenic superconductors, and this introduces considerable uncertainty in the values of λ obtained by TF µSR.

Transport from the endoplasmic reticulum to the Golgi.

Two crucial aspects of transport vesicle function have recently been reconstituted using purified proteins and chemically defined lipid bilayers. The reconstituted steps are the assembly of a polymeric protein coat on the cytosolic surface of the membrane, and bilayer fusion based on the pairing of proteins in the vesicle and target membrane. These advances now set the stage to address major unresolved questions of how vesicle budding and vesicle fusion are regulated, how specific cargo molecules are incorporated into vesicles, and how vesicles find their target membrane.