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Biomedical subjects

J Grimm

Publications and source records attributed to J Grimm.

At least 19 recordsLinked to original sources

Upconversion Between 4f-5d Excited States in Tm2+-Doped CsCaCl3, CsCaBr3, and CsCaI3.

Near-infrared to visible upconversion luminescence in CsCaCl3:Tm2+, CsCaBr3:Tm2+ and CsCaI3:Tm2+ is presented and analysed. The upconversion process involves exclusively the 4f-5d excited states of Tm2+, which is a novelty among upconversion materials. The presence of more than one long-lived 4f-5d excited state is the prerequisite for this. Multiple emissions from Tm2+ are observed in the title compounds. This is made possible by the favourable energy structure within the 4f-5d states and the low phonon energies of the materials. The energy positions of the relevant 4f-5d states, and thus the photophysical and light emission properties, are affected by the chemical variation along the series. The upconversion efficiency increases from chloride to iodide and the mechanism is found to be a combination of absorption and energy-transfer steps.

Journal Article↗

[Cell tracking. Principles and applications].

Cell based therapies such as stem cell therapies or adoptive immunotherapies are currently being explored as a potential treatment for a variety of diseases such as Parkinson's disease, diabetes or cancer. However, quantitative and qualitative evaluation of adoptively transferred cells is indispensable for monitoring the efficiency of the treatment. Current approaches mostly analyze transferred cells from peripheral blood, which cannot assess whether transferred cells actually home to and stay in the targeted tissue. Using cell-labeling methods such as direct labeling or transfection with a marker gene in conjunction with various imaging modalities (MRI, optical or nuclear imaging), labeled cells can be followed in vivo in real-time, and their accumulation as well as function in vivo can be monitored and quantified accurately. This method is usually referred to as "cell tracking" or "cell trafficking" and is also being applied in basic biological sciences, exemplified in the evaluation of genes contributing to metastasis. This review focuses on principles of this promising methodology and explains various approaches by highlighting recent examples.

Cell Separation↗

[Current state of molecular imaging research].

The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly non-specific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments.

Animals↗

Mouse models of human non-small-cell lung cancer: raising the bar.

Lung cancer is a devastating disease that presents a challenge to basic research to provide new steps toward therapeutic advances. The cell-type-specific responses to oncogenic mutations that initiate and regulate lung cancer remain poorly defined. A better understanding of the relevant signaling pathways and mechanisms that control therapeutic outcome could also provide new insight. Improved conditional mouse models are now available as tools to improve the understanding of the cellular and molecular origins of adenocarcinoma. These models have already proven their utility in proof-of-principle experiments with new technologies including genomics and imaging. Integrated thinking to apply technological advances while using the appropriate mouse model is likely to facilitate discoveries that will significantly improve lung cancer detection and intervention.

Animals↗

Guidelines on radioiodine therapy for differentiated thyroid carcinoma: impact on clinical practice.

AIM: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing Multicenter Study Differentiated Thyroid Carcinoma (MSDS) were analyzed. PATIENTS, METHODS: Patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pN0/1/x M0/x (UICC, 5th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131I whole-body scintigraphy (WBS) 3-4 months after RIT. RESULTS: Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131I activity for RIT (1-3 vs. 1-4 GBq; +/- 10%), and in 16% and 60% with regard to 131I activity for WBS (100-300 vs. 100-400 MBq; +/- 10%). CONCLUSIONS: The 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes.

Combined Modality Therapy↗

Percutaneous management of occlusive arterial disease associated with vasculitis: a single center experience.

The purpose of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty for occlusive arterial disease associated with vasculitis. Eleven patients (10 women, 1 man; ages 35-82 years) with the diagnosis of vasculitis of the large vessels underwent interventional treatment during intraarterial angiography. The causes included giant cell arteritis (n = 8) and Takayasu arteritis (n = 3). Thirty-three occlusive lesions (including brachiocephalic and renal arteries, and arteries of upper and lower extremities) were treated with balloon angioplasty and/or stent placement. Follow-up included clinical examination, angiography, and color duplex ultrasound. Technical success was 100% (25/25) for stenoses and 50% (4/8) for occlusive lesions, representing all lesions combined from different anatomic locations. Dissection (n = 3) and arterial rupture with retroperitoneal hematoma (n = 1) was found in three patients. During follow-up (mean 12 months), restenoses (n = 8) and re-restenoses (n = 1) occurred in 8 vascular areas. Three of these lesions were treated with repeated PTA (n = 4). The cumulative primary clinical success rate was 67.6%, cumulative secondary success rate 74.4%, and cumulative tertiary success rate 75.9%. Interventional therapy in systemic vasculitis provides promising results in technical success rates and followup. Angioplasty may result in arterial injury, but the rate of complications is low.

Adult↗

[Molecular imaging in rheumatoid arthritis].

Advances in molecular biology and technical developments in the field of imaging are increasingly allowing for non-invasive visualization and quantitation of biological processes at the molecular level. Such technologies, defined as molecular imaging, promise early diagnosis and improved classification of the stage and severity of disease, objective assessment of treatment efficacy, and reliable prognosis based on so-called molecular markers. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes and for drug development. Various different imaging modalities are available, such as conventional radiography (CR), computed tomography (CT), nuclear imaging, magnetic resonance imaging (MRI), ultrasound (US), as well as other methods including fluorescence-based optical imaging. These methods differ with respect to resolution and their potential to gather information at the anatomical, physiological, cellular and molecular level. Therefore, the choice of the imaging modality for molecular imaging depends on the questions that need to be answered. This review discusses the potential of imaging modalities for molecular imaging in rheumatoid arthritis (RA).

Animals↗

[In-vitro comparison of the effectiveness of different high-speed rotatory catheters].

OBJECTIVE: To determine the in vitro effectiveness of the Amplatz and Rotarex catheters for thrombus fragmentation and combined thrombus fragmentation and aspiration. MATERIALS AND METHODS: Clots (n = 100) from 5-day-old porcine blood (8.5 g) were fragmented with the 8F Rotarex trade mark catheter (RR; 40.000 rpm), which was directed with or without a coaxial guide wire (GW 0.020 inch [8 F RR(GW)], GW 0.014 inch [6 F RR(GW)]), and with the 7 F Amplatz catheter (ATD; 150.000 rpm), in an artery flow model (pulsed flow of 700 ml/min) simulating the superficial femoral artery. To increase the wall adherence of the thrombus, an additional equal number of silicon tubes (with an inner diameter of 7 mm) were fitted inside with a metallic mesh (wall-adherent thrombus [WAT]; 6 F RR(WAT), 8 F RR(WAT), 6 F R(WAT-GW), 8 F RR(WAT-GW), ATD(WAT) ). The effluent was passed through a three-step filter system (10 to 1000 micro m; pressure gradient 35 mmHg). RESULTS: Highest effectiveness was found for 8 F RR (no remaining thrombus detectable) compared to 6 F RR (0.08 g) and ATD (0.07 g), with a p < 0.001 for both methods. The aspirated volume was significantly lower when 6 F and 8 F RR were used with a coaxial guide wire (p < 0.001). The total emboli rate for 8 F RR was significantly lower compared to ATD (p < 0.001). Even when working without a guide wire, 8 F RR caused the lowest proportion of emboli (depending on the modification 0.12 % to 1.76 %; compared to all p < 0.05). Emboli rates reached 7.99 % for 6 F RR (compared to all p < 0.001) and were maximal 5.61 % for ATD. CONCLUSIONS: The tested mechanical thrombectomy catheters have a high potential for in vitro thrombectomy with moderate performance differences. In contrast to the guidewire-directed Rotarex fragmentation-aspiration device, the ATD trade mark fragmentation catheter and prototype Rotarex 6 F catheter have a considerable peripheral embolization rate of particles larger than 1000 micro m, probably requiring additional measures for in vivo thrombectomy.

Animals↗

Selective water excitation for faster MR imaging of articular cartilage defects: initial clinical results.

Our objective was to compare a water-excitation (WE) 3D fast low-angle shot (FLASH) MR sequence for faster imaging of articular cartilage defects of the knee to a conventional fat-saturated (FS) 3D FLASH MR sequence. This prospective study included 16 knees of 16 patients with suspected cartilage lesions. The MR imaging in transverse and sagittal planes included (a) FS 3D FLASH (TR/TE: 45 ms/11 ms, scan time 8 min, flip angle 50 degrees), and (b) WE 3D FLASH (TR/TE: 28 ms/11 ms, scan time 4 min 58 s, flip angle 40 degrees). For each sequence signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were quantified. The detected cartilage lesions were evaluated using a semi-quantitative four-scale scoring system (grades 0-III). The data were compared between the sequences using the paired Student's t-test. No statistically significant differences between the sequences were found for SNR, CNR, and cartilage defect grading (p=0.14-0.8). The WE 3D FLASH MR imaging seems to be promising for fast imaging of articular cartilage lesions of the knee.

Cartilage Diseases↗

[Early results with a monorail-stent-balloon device for endovascular treatment of renal artery stenosis].

OBJECTIVE: To evaluate the technical feasibility of a new monorail-stent-balloon device for treatment of renal artery stenosis (RAS). PATIENTS AND METHODS: During a study period of 18 months, 38 patients with proven RAS in 41 cases (hypertension n = 36, renal insufficiency n = 13) and indication for stenting (calicified ostial lesions n = 35, insufficient PTA n = 4, dissection n = 2) were enrolled into this prospective evaluation. Pre-mounted stents (Rx-Herculink(TM) 5 mm = 13, 6 mm = 34, 7 mm = 1) were implanted a transfemoral (n = 35) or transbrachial approach (n = 6). Mean grade and lengths of stenosis measured were 88 % plus minus 10 and 9 mm plus minus 5. RESULTS: Renal stent implantation was technically successful in all cases (100 %). In 7 cases a second stent had to be implanted to cover the entire lesion. The transstenotic pressure drop decreased from 88 mmHg plus minus 10 before to 1 mmHg plus minus 1.8 after the procedure. Remaining stenosis measured 0.7 % plus minus 4.2. Serum creatine levels decreased from 1.9 mm/dl to 1.5 mg/dl (n. s.), blood pressure decreased from 178/94 mmHg to 148/79 mmHg (p < 0.0001) after the intervention. Primary and secondary patency rates at 6 months were 72 % (Standard Error 9.8 %) and 77 (% (Standard Error 9.2 %), respectively. CONCLUSION: With the used monorail-stend-balloon device a technically easy, secure and exact renal stent placement is guaranteed, patency rates are similar to those described in the current literature.

Adult↗

[Alar ligaments: radiological aspects in the diagnosis of patients with whiplash injuries].

Post-traumatic changes of the alar ligaments have been proposed to be the cause of chronic pain in patients after whiplash injury of the cervical spine. In addition to an asymmetric dens position, widening of the atlantodental distance to more than 12 mm can be an indirect sign of an alar ligament rupture. CT is recommended for detection of a avulsion fracture of the occipital condyle. Isolated ruptures of the alar ligaments are best visualized on MRI. In patients with chronic impairments after whiplash injuries changes of the alar ligaments on MRI must be differentiated from normal variants in healthy individuals.

Adult↗

[Sensitivity of MRI in detecting alveolar Infiltrates: Experimental studies].

PURPOSE: An experimental study using porcine lung explants and a dedicated chest phantom to evaluate the signal intensity of artificial alveolar infiltrates with T 1 - and T 2 -weighted MRI sequences. MATERIAL AND METHODS: 10 porcine lung explants were intubated, transferred into the cavity of a MRI-compatible chest phantom and inflated by continuous evacuation of the artificial pleural space. All lungs were examined with MRI at 1.5 T before and after intra-tracheal instillation of either 100 or 200 ml gelatine-stabilised liquid to simulate alveolar infiltrates. MR-examination comprised gradient echo (2D- and 3D-GRE) and fast spin echo sequences (T 2 -TSE and T 2 -HASTE). The signal intensity of lung parenchyma was evaluated at representative cross sections using a standardised scheme. Control studies were acquired with helical CT. RESULTS: The instilled liquid caused patchy confluent alveolar infiltrates resembling the findings in patients with pneumonia or ARDS. CT revealed typical ground-glass opacities. Before the application of the liquid, only T 2 -HASTE and T 2 -TSE displayed lung parenchyma signals with a signal/noise ratio of 3.62 and 1.39, respectively. After application of the liquid, both T 2 -weighted sequences showed clearly visible infiltrates with an increase in signal intensity of approx. 30 % at 100 ml (p < 0.01) and 60 % at 200 ml (p < 0.01). With 2D- and 3D-GRE the infiltrates were not visible, although the lung parenchyma signal increase was statistically significant. On 2D-GRE the increase in signal intensity reached 0.74 % (p = 0.32) after 100 ml and 5.6 % (p < 0.01) after 200 ml (for 3D-GRE: 2.2 % [p = 0.02] at 100 ml and 4.4 % at 200 ml [p < 0.01]). The CT controls revealed a significant increase of lung density of 17 H.E. at 100 ml (p = 0.02) and 75 H.E. at 200 ml (p < 0.01). CONCLUSIONS: MRI with T 2 -weighted sequences detects artificial alveolar infiltrates with high signal intensity and may be a highly sensitive tool to detect pneumonia in patients.

Animals↗

Analysis of artefacts and detail resolution of lung MRI with breath-hold T1-weighted gradient-echo and T2-weighted fast spin-echo sequences with respiratory triggering.

The aim of this study was to evaluate feasibility and limitations of two MR sequences for imaging of the lung using a semi-quantitative rating scale. Ten healthy volunteers were assessed with a breath-hold T1-weighted gradient-recalled-echo (TR/TE=129/2.2 ms, matrix 173 x 256) and a T2-weighted turbo spin-echo (TSE) sequence with respiratory triggering (TR/TE=3000-5000/120 ms, matrix 270 x 512) in axial 6-mm slices. The T1-weighted GRE protocol included a pre-saturation pulse over the mediastinal structures. Artefacts and resolution of vessel/airway structures in each lung segment were evaluated by two observers (10 volunteers, 180 segments). Cardiac and vessel pulsation artefacts predominated on T1-weighted GRE, respiration artefacts on T2-weighted TSE (lingula and middle lobe). Pre-saturation of the mediastinum reduced pulsation artefacts on T1-weighted GRE. T1-weighted GRE images were improved by bright flow signal of vessels, whereas image quality of T2-weighted TSE was reduced by black-blood effects in central parts of the lung. Delineation of lung periphery and the mediastinum was superior with T2-weighted TSE. Segmental/sub-segmental vessels (up to fourth/fifth order) and bronchi (up to third order) were identified. All 180 lung segments were imaged in diagnostic quality with at least one of the two sequences (T1-weighted GRE not diagnostic in 9 of 180, T2-weighted TSE in 4 of 180). Both sequences were found to be complementary: superior identification of gross lung anatomy with T1-weighted GRE and higher detail resolution in the periphery and the mediastinum with T2--weighted TSE.

Adult↗

Sentinel node procedure in Ib cervical cancer: a preliminary series.

The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium(99)m-labelled nanocolloid in each quadrant of the cervix. Dynamic and static images were recorded using a gamma camera. SLNs were identified intraoperatively using a handheld gamma-detection probe. After resection of SLNs a standard radical hysterectomy with pelvic lymph node dissection was performed. Patients and tumour characteristics were compared with sentinel node detection and with final histopathological and immunohistochemical results. Scintigraphy showed focal uptake in 13 of the 14 patients. Intraoperatively we detected 26 sentinel nodes by gamma probe. In 8 of 13 patients, one or more sentinel nodes were identified unilaterally, in 5 women bilaterally. Histologically positive SLNs were found in only 1 patient. We did not find any false-negative SLN in our series. In conclusion identification of sentinel nodes in cervical cancer is feasible with preoperatively administered technetium(99)m-labelled nanocolloid. A larger series will be required to establish sentinel node detection in cervical cancer for further therapy concepts and planning.

Adenocarcinoma↗

Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation.

Docking proteins are substrates of tyrosine kinases and function in the recruitment and assembly of specific signal transduction molecules. Here we found that p62dok family members act as substrates for the c-Ret receptor tyrosine kinase. In addition to dok-1, dok-2, and dok-3, we identified two new family members, dok-4 and dok-5, that can directly associate with Y1062 of c-Ret. Dok-4 and dok-5 constitute a subgroup of dok family members that is coexpressed with c-Ret in various neuronal tissues. Activated c-Ret promotes neurite outgrowth of PC12 cells; for this activity, Y1062 in c-Ret is essential. c-Ret/dok fusion proteins, in which Y1062 of c-Ret is deleted and replaced by the sequences of dok-4 or dok-5, induce ligand-dependent axonal outgrowth of PC12 cells, whereas a c-Ret fusion containing dok-2 sequences does not elicit this response. Dok-4 and dok-5 do not associate with rasGAP or Nck, in contrast to p62dok and dok-2. Moreover, dok-4 and dok-5 enhance c-Ret-dependent activation of mitogen-activated protein kinase. Thus, we have identified a subclass of p62dok proteins that are putative links with downstream effectors of c-Ret in neuronal differentiation.

Adaptor Proteins, Signal Transducing↗

Bioequivalence investigation of high-dose etoposide and etoposide phosphate in lymphoma patients.

PURPOSE: To compare etoposide pharmacokinetics following administration of high-dose etoposide and etoposide phosphate, a water-soluble prodrug of etoposide. Bioequivalence was assessed using a two-treatment randomized crossover design. METHODS: Ten patients with high-risk or relapsed lymphoma were treated with a sequential high-dose chemotherapy. They were randomized to receive either 3 x 400 mg/m2 etoposide or an equimolar amount of etoposide phosphate (as 1-h infusions on three consecutive days) in the first course and the alternative drug in the second course. Serial plasma and ultrafiltered plasma samples were collected and analysed for etoposide by a reversed-phase HPLC method with UV and electrochemical detection. Pharmacokinetic parameters were estimated using a two-compartment model. Bioequivalence was assessed calculating the 90% confidence intervals (CI) for the ratios of the geometric means of AUC(0-infinity) and additionally of Cmax of etoposide derived from etoposide phosphate relative to etoposide in plasma and ultrafiltered plasma as point estimates (level of significance alpha < 0.05). RESULTS: Pharmacokinetic parameters of etoposide were comparable in both treatment arms except that terminal half-life was significantly shorter and apparent Vss in ultrafiltered plasma was significantly larger following administration of the prodrug. The point estimates for AUC(0-infinity) of etoposide derived from etoposide phosphate relative to etoposide were 102.9% and 88.4% for plasma and ultrafiltered plasma, respectively. The 90% CIs were in the range from 80% to 125% where bioequivalence can be assumed. The point estimates of Cmax on day 3 of chemotherapy were 96.5% and 81.7% in plasma and ultrafiltrate with the 90% CI in ultrafiltered plasma being out of the range from 80% to 125%. CONCLUSION: With respect to total drug exposure, represented by AUC(0-infinity), high-dose etoposide phosphate is bioequivalent to high-dose etoposide.

Adult↗

Flow patterns from metallic vascular endoprostheses: in vitro results.

The aim of this study was to determine flow characteristics and pressure gradients of different balloon- and self-expandable stents in an in vitro flow-model. Seven vascular stents (Bridge, Cragg, Memotherm, Palmaz PS 784, Sinus, Symphony, Wallstent), equal in length (60 mm) and diameter (10 mm), were deployed in a closed flow model. The inner diameter of the tube measured 9 mm. Flow at 1.5 and 6 l/min was applied. Flow patterns were visualized by anionic particles illuminated with two helium-neon lasers. Late laminary flow characteristics and pre-/post-stent pressure gradients were determined in either expanded stent, 25 and 50% tube stenosis. Stent implantation induced a decrease of laminary flow when compared with an unstented tube with and without concentric 25% stenosis (p < 0.01) at all flow rates and an increase of pressure gradients when compared with an unstented tube for a flow rate of 6 l/min and all stenoses (p < 0.01). At 1.5 l/min most stents revealed no significant change of pressure gradient, the highest gradient measured 4.0 mmHg. Sinus permitted maximum (expanded: 82.1% and 76.9% at 25% stenosis at 1.5 l/min; p < 0.01) and Palmaz minimum of laminary flow at all flow rates and stenoses (70.2 and 52.4% at 25% stenosis at 1.5 l/min; p < 0.01). At 6 l/min, when completely expanded, Sinus is equal to Bridge and Memotherm; in 25% stenosis Sinus is equal to Bridge, Memotherm, and additionally to Cragg and Wall. None of the endoprostheses revealed laminary flow at 50% stenosis. Inadequate stent deployment bears the risk of creating less laminary flow and pressure gradients. Since flow disturbances and pressure gradients may influence neointimal hyperplasia, stent design and completeness of stent expansion are important factors regarding the appearance of thrombus formation and postinterventional restenosis.

Arteries↗

Evaluation of hydroxyapatite implants in vertebral bodies and extremities by contrast-enhanced magnetic resonance imaging.

This pilot study evaluated hydroxyapatite (HA) implants (Endobon) into bone with magnetic resonance imaging (MRI). Nineteen patients (median age 57 years; range 18-67 years) have been evaluated. Eight received granulated HA into vertebral bodies after trauma, while 11 received HA blocks into extremity bones after trauma (n = 8) or fibrous dysplasia (n = 2). In a 1.5-T MR scanner, transversal T1-weighted, flash, 2-dimensional images were obtained. Signal intensities were measured in regions of interest (ROI) from the centre and periphery of HA, trabecular bone, fat and air before and after gadolinium (Gd) contrast enhancement, and the signal-to-noise ratio (SNR) was calculated. After Gd application the SNR in HA increased significantly, peripherally (11.7 without vs 18.2 with Gd, P = 0.003) more than in the centre (7.9 without vs 11.9 with Gd, P = 0.007). The SNR of the HA was higher in patients with block implants compared with granulated HA (P > 0.008). After Gd application, granulated HA enhances significantly less than HA blocks. During insertion of HA, the granulated form is compressed more and is therefore more compact than the HA block. This might hinder integration into the bone structure and the blood supply. SNR of the HA margin was higher than centrally, which might be due to granulomatous tissue after trauma and/or operation or beginning marginal integration.

Adolescent↗