Anzeige
Mehr »
Mittwoch, 27.08.2025 - Börsentäglich über 12.000 News
Patentschutz bis in die 2040er - Biotech-Geheimtipp vor möglichem Fast-Track-Durchbruch in den USA!
Anzeige

Indizes

Kurs

%
News
24 h / 7 T
Aufrufe
7 Tage

Aktien

Kurs

%
News
24 h / 7 T
Aufrufe
7 Tage

Xetra-Orderbuch

Fonds

Kurs

%

Devisen

Kurs

%

Rohstoffe

Kurs

%

Themen

Kurs

%

Erweiterte Suche
PR Newswire
386 Leser
Artikel bewerten:
(2)

DelveInsight Business Research, LLP: Glioblastoma Multiforme Market to Grow Significantly at a CAGR of 13.1% During the Forecast Period (2022-2032) | DelveInsight

The glioblastoma multiforme market is expected to witness a significant positive shift owing to the positive outcomes of the several products during the developmental stage by key players such as Bayer, VBL Therapeutics, AstraZeneca, DNAtrix, Kintara Pharmaceuticals, Chimerix, Karyopharm, VBI Vaccines, Kazia Therapeutics, Aivita Biomedical, Medicenna Therapeutics, Immunomic Therapeutics, Istari Oncology, Inovio Pharmaceuticals, Northwest Biotherapeutics, and others.

LAS VEGAS, Nov. 28, 2022 /PRNewswire/ -- DelveInsight's Glioblastoma Multiforme Market Insights report includes a comprehensive understanding of current treatment practices, glioblastoma multiforme emerging drugs, market share of individual therapies, and current and forecasted market size from 2019 to 2032, segmented into 7MM [the United States, the EU-4 (Italy, Spain, France, and Germany), the United Kingdom, and Japan].

DelveInsight_Logo

Key Takeaways from the Glioblastoma Multiforme Market Report

  • As per DelveInsight analysis, the glioblastoma multiforme market size in the 7MM was approximately USD 799 million in 2021.
  • According to the assessment done by DelveInsight, the estimated total glioblastoma multiforme incident cases in the 7MM were approximately 32.5K in 2021.
  • Leading glioblastoma multiforme companies such as Bayer, Chimerix, Aivita Biomedical, Denovo Biopharma, Northwest Biotherapeutics, VBL Therapeutics, Laminar Pharmaceuticals, MedImmune, DNAtrix, Immunomic Therapeutics, Imvax, MimiVax, CNS Pharmaceuticals, Epitopoietic Research Corporation (ERC), Istari Oncology, SonALAsense, Kintara Therapeutics, Bristol Myers Squibb, Medicenna Therapeutics, BioMimetix, Eisai and Merck Sharp & Dohme, Kazia Therapeutics, Oblato, Genenta Science, Enterome, Inovio Pharmaceuticals, Karyopharm Therapeutics, Forma Therapeutics, VBI Vaccines, TME Pharma, Novocure, Genentech, Daiichi Sankyo, Novartis, and others are developing novel glioblastoma drugs that can be available in the glioblastoma multiforme market in the coming years.
  • The promising glioblastoma multiforme therapies in the pipeline include Regorafenib, ONC201, AV-GBM-1, Enzastaurin (DB-102), DCVax-L, LAM561 (2-OHOA), Tasadenoturev (DNX-2401), ITI-1000 (pp65 DC Vaccine), SurVaxM, Berubicin, GLIOVAC (Sitoiganap), Lerapolturev + Pembrolizumab, VAL-083 (dianhydrogalactitol), MDNA55, Paxalisib (GDC-0084), Temferon, EO2401, INO-5401 + INO-9012 + LIBTAYO (cemiplimab), Delytact (Teserpaturev/DS-1647), TAFINLAR + MEKINIST, VBI-1901, and others.
  • The current therapeutic landscape of GBM in the United States is driven by the current treatment paradigm, which includes therapies such as radiation, bevacizumab, temozolomide, and OPTUNE, as mono or combination therapies, as well as several other systemic therapies.
  • In October 2022, NovAccess Global's TLR-AD1 Orphan Drug Application was approved by the FDA. The FDA broadens the scope of the company's submission, accelerating the path to immunotherapy for glioblastoma.
  • In October 2022, Black Diamond Therapeutics announced the presentation of three posters reporting new preclinical data on BDTX-1535 and BDTX-4933 at the 34th European Organization for Research and Treatment of Cancer-National Cancer Institute-American Association for Cancer Research (EORTC-NCI-AACR) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.
  • In October 2022, Oblato, a Korean subsidiary of HLB Therapeutics, announced that it has completed enrollment of recurrent GBM patients in Phase II clinical trial with its proprietary compound OKN-007 in the United States.
  • In August 2022,Northwest Biotherapeutics announced that the Pediatric Investigation Plan (PIP) had been approved by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). The company's approved PIP includes two clinical trials: one for newly diagnosed pediatric HGG, and one for recurrent pediatric HGG. In each of the two pediatric trials, 24 patients will be treated with DCVax-L on the same treatment schedule as in the company's Phase III trial in adult glioblastoma patients.
  • In June 2022, Novartis announced that the US FDA had granted TAFINLAR (dabrafenib) + MEKINIST (trametinib) accelerated approval for the treatment of advanced tumors with the "BRAF V600E" mutation. The approval includes use in both adult and pediatric (over the age of six) high- and low-grade glioma patients with this mutation whose tumors progressed after prior treatment.
  • In May 2022, Kintara Therapeutics announced that the VAL-083 treatment arm in the GBM adaptive global innovative learning environment (GBM AGILE) registrational Phase II/III clinical trial for GBM had activated its first European site.
  • In November 2021, Chimerix announced positive data in recurrent H3 K27M-mutant Diffuse Midline Glioma to be presented at the Society for Neuro-Oncology Annual Meeting.

Discover which therapies are expected to grab the major glioblastoma multiforme market share @Glioblastoma Multiforme Market Report

Glioblastoma Multiforme Overview

Glioblastoma, also known as glioblastoma multiforme is a cancer that can develop in the brain or spinal cord. Glioblastoma develops from astrocytes, which are nerve cell-feeding cells. It can occur at any age, but it is more common in the elderly. It can make headaches, nausea, vomiting, and seizures worse. The causes of glioblastoma are unknown.

Glioblastoma symptoms vary depending on tumor type, size, location, and growth rate. Headache, nausea or vomiting, confusion or deterioration in brain function, memory loss, personality changes or irritability, and difficulty balancing are all common glioblastoma symptoms. Computed tomography (CT or CAT scan) and magnetic resonance imaging (MRI) are two diagnostic tools used for glioblastoma diagnosis. Glioblastoma treatments may slow cancer progression and alleviate symptoms.

Glioblastoma Multiforme Epidemiology Segmentation

DelveInsight estimates that there were approximately 32.5Kincident cases of glioblastoma multiforme in the 7MM in 2021.

Among the EU-4 countries, the incident population of GBM was found to be the maximum in Germany in 2021.

The glioblastoma multiforme market report proffers epidemiological analysis for the study period 2019-2032 in the 7MM segmented into:

  • Total Incident Cases
  • Gender-specific Incident Cases
  • Type-specific Incident Cases
  • Age-specific Incident Cases
  • Incident Cases based on Primary Site of GBM
  • Incident Cases based on Histologic Classification of GBM

Download the report to understand which factors are driving glioblastoma multiforme epidemiology trends @Glioblastoma Multiforme Epidemiological Insights

Glioblastoma Multiforme Treatment Market

Glioblastoma multiforme is typically treated with a combination of surgery, chemotherapy, radiation, or stereotactic radiosurgery. Although rarely used alone, surgery is usually one of the most important aspects of glioblastoma treatment. Because glioblastomas grow so quickly, they are frequently difficult to remove completely. As a result, surgery is performed to achieve the best possible safe resection - removing as much of the tumor as possible while preserving brain function and sparing healthy tissues. Following surgery, residual cancer cells can be targeted with additional treatments such as chemotherapy or radiation therapy. Once the tumor's diagnosis or name is determined, radiation therapy and chemotherapy are usually administered.

These are known as adjuvant glioblastoma treatments. Because this multispecialty approach can have several side effects, steroids are frequently used as an additional component of glioblastoma treatment to help alleviate the side effects of other therapies.

Chemotherapy is a common type of glioblastoma treatment. Patients typically begin chemotherapy 2-4 weeks after surgery, at the same time as or shortly after radiation therapy. When a tumor cannot be surgically removed, chemotherapy is sometimes used as the primary glioblastoma treatment.

Cytotoxic drugs include Carmustine (BCNU), Lomustine (CCNU), or Gleostine (Generic), Gliadel wafer (biodegradable discs infused with BCNU), Temozolomide (Temodar), Cisplatin, Carboplatin, Etoposide, and Irinotecan.

To know more about glioblastoma treatment options, visit @Glioblastoma Treatment Drugs

Glioblastoma Multiforme Pipeline Therapies and Key Companies

  • Regorafenib: Bayer
  • ONC201: Chimerix
  • AV-GBM-1: Aivita Biomedical
  • Enzastaurin (DB-102): Denovo Biopharma
  • DCVax-L: Northwest Biotherapeutics
  • Ofranergene Obadenovec (VB-111): VBL Therapeutics
  • LAM561 (2-OHOA): Laminar Pharmaceuticals
  • MEDI4736 (durvalumab): MedImmune
  • Tasadenoturev (DNX-2401): DNAtrix
  • ITI-1000 (pp65 DC Vaccine): Immunomic Therapeutics
  • IGV-001: Imvax
  • SurVaxM: MimiVax
  • Berubicin: CNS Pharmaceuticals
  • GLIOVAC (Sitoiganap): Epitopoietic Research Corporation (ERC)
  • Lerapolturev + Pembrolizumab: Istari Oncology
  • SONALA-001 + Exablate 2.0 Device: SonALAsense
  • VAL-083 (dianhydrogalactitol): Kintara Therapeutics
  • Pomalidomide: Bristol Myers Squibb
  • MDNA55: Medicenna Therapeutics
  • BMX-001: BioMimetix
  • Lenvatinib ± Pembrolizumab: Eisai and Merck Sharp & Dohme
  • Paxalisib (GDC-0084): Kazia Therapeutics
  • OKN-007: Oblato
  • Temferon: Genenta Science
  • EO2401: Enterome
  • INO-5401 + INO-9012 + LIBTAYO (cemiplimab): Inovio Pharmaceuticals
  • Selinexor (KPT-330): Karyopharm Therapeutics
  • Olutasidenib (FT-2102): Forma Therapeutics
  • VBI-1901: VBI Vaccines
  • Olaptesed pegol (NOX-A12): TME Pharma

Learn more about the glioblastoma FDA-approved drugs @Drugs for Glioblastoma Treatment

Glioblastoma Multiforme Market Dynamics

The dynamics of glioblastoma multiforme market is predicted to change in the coming years owing to the improvement in the research and development activities so that glioblastoma multiforme market will comprise of efficient glioblastoma treatment options. Moreover, the anticipated launch of emerging therapies during the forecast period is further expected to fuel the glioblastoma multiforme market growth.

Furthermore, vaccine approaches are appealing as adjuvant therapy for solid tumors because they can generate long-term immune surveillance against cancer cells. MimiVax (SurVaxM), Immunomic Therapeutics (ITI-1000), and IMVAX (IGV-001) are among the companies developing therapeutic vaccines for glioblastoma multiforme.

Forbye, the introduction of bevacizumab biosimilars has resulted in a decrease in the cost burden. Numerous failed clinical trials indicate that combination therapies are likely to be the most promising method of glioblastoma treatment, with an emphasis on drug design and pharmacokinetic properties. Furthermore, better prognostic markers would allow physicians to diagnose and treat GBM earlier, potentially preventing disease progression and thereby boosting the glioblastoma multiforme market growth.

However, several factors are impeding the growth of the glioblastoma multiforme market. There is a lack of a reliable biomarker that can aid in the diagnosis, patient stratification, recurrence detection, and therapy response. As a result, biomarkers are required to overcome the disease's complexity and allow for minimally invasive detection and analysis.

As the glioblastoma multiforme market lacks an effective strategy for curing GBM, the survival rate of patients diagnosed with GBM remains low. Even after using approved therapies, GBM patients have a low survival rate.

Furthermore, gliomas' molecular and cellular complexity severely limits diagnosis and treatment. This is exacerbated by significant intertumoral and intratumoral heterogeneity, which has a negative impact on the ability to develop effective and reliable disease biomarkers. Hence these factors mentioned above may hinder the growth of the glioblastoma multiforme market.

Report Metrics

Details

Study Period

2019-2032

Coverage

7MM [The United States, the EU-4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]

Base Year

2021

Glioblastoma Multiforme Market CAGR

13.1 %

Glioblastoma Multiforme Market Size in 2021

USD 799 million

Key Glioblastoma Multiforme Companies

Bayer, Chimerix, Aivita Biomedical, Denovo Biopharma, Northwest Biotherapeutics, VBL Therapeutics, Laminar Pharmaceuticals, MedImmune, DNAtrix, Immunomic Therapeutics, Imvax, MimiVax, CNS Pharmaceuticals, Epitopoietic Research Corporation (ERC), Istari Oncology, SonALAsense, Kintara Therapeutics, Bristol Myers Squibb, Medicenna Therapeutics, BioMimetix, Eisai and Merck Sharp & Dohme, Kazia Therapeutics, Oblato, Genenta Science, Enterome, Inovio Pharmaceuticals, Karyopharm Therapeutics, Forma Therapeutics, VBI Vaccines, TME Pharma, Novocure Limited, Genentech, Daiichi Sankyo, Novartis, and others

Key Pipeline Glioblastoma MultiformeTherapies

Regorafenib, ONC201, AV-GBM-1, Enzastaurin (DB-102), DCVax-L, Ofranergene Obadenovec (VB-111), LAM561 (2-OHOA), MEDI4736 (durvalumab), Tasadenoturev (DNX-2401), ITI-1000 (pp65 DC Vaccine), IGV-001, SurVaxM, Berubicin, GLIOVAC (Sitoiganap), Lerapolturev + Pembrolizumab, SONALA-001 + Exablate 2.0 Device, VAL-083 (dianhydrogalactitol), Pomalidomide, MDNA55, BMX-001, Lenvatinib ± Pembrolizumab, Paxalisib (GDC-0084), OKN-007, Temferon, EO2401, INO-5401+ INO-9012+ LIBTAYO (cemiplimab), Selinexor (KPT-330), Olutasidenib (FT-2102), VBI-1901, NOX-A12/olaptesed pegol, and others

Scope of the Glioblastoma Multiforme Market Report

  • Therapeutic Assessment: Glioblastoma Multiforme current marketed and emerging therapies
  • Glioblastoma Multiforme Market Dynamics: Glioblastoma Multiforme market drivers and barriers
  • Competitive Intelligence Analysis: SWOT analysis, PESTLE analysis, Porter's five forces, BCG Matrix, Market entry strategies
  • Unmet Needs, KOL's views, Analyst's views, Glioblastoma Multiforme Market Access and Reimbursement

Discover more about glioblastoma drugs in development @Glioblastoma Clinical Trials

Table of Contents

1

Key Insights

2

Report Introduction

3

Glioblastoma Multiforme Market Overview at a Glance

3.1

Market Share (%) Distribution of GBM in 2019 by Countries

3.2

Market Share (%) Distribution of GBM in 2032 by Countries

4

Epidemiology and Market Forecast Methodology

5

Executive Summary of Glioblastoma Multiforme (GBM)

6

Key Events

7

SWOT Analysis

8

Disease Background and Overview: Glioblastoma Multiforme

8.1

Introduction

8.2

Classification of Glioblastoma Multiforme

8.3

Glioblastoma Types

8.4

Symptoms

8.5

Pathophysiology

8.6

Inheritance of Glioblastoma Multiforme

8.7

Molecular Classification

8.8

Diagnosis of Glioblastoma Multiforme

9

Treatment

9.1

Surgery

9.2

Chemotherapy

9.3

Radiation

9.4

Others

9.5

Management of Symptoms with Medication

9.6

Treatment Algorithm

10

Guidelines and Recommendations from Different Organizations

11

Epidemiology and Patient Population

11.1

Key Findings

11.2

Total Incident Cases of GBM in the 7MM

11.3

Assumptions and Rationale

11.4

United States

11.4.1

Total Incident Cases of GBM in the United States

11.4.2

Gender-specific Incidence Cases of GBM in the United States

11.4.3

Type-specific Incidence Cases of GBM in the United States

11.4.4

Age-specific Incidence Cases of GBM in the United States

11.4.5

Incident Cases based on Primary Site of GBM in the United States

11.4.6

Incident Cases based on Histologic Classification of GBM Tumor in the United States

11.5

EU-4 and UK

11.5.1

Total Incident Cases of GBM in the EU-4 and the UK

11.5.2

Gender-specific Incidence Cases of GBM in the EU-4 and the UK

11.5.3

Type-specific Incidence Cases of GBM in the EU-4 and the UK

11.5.4

Age-specific Incidence Cases of GBM in the EU-4 and the UK

11.5.5

Incident Cases Based on Primary Site of GBM in the EU-4 and the UK

11.5.6

Incident Cases based on Histologic Classification of GBM Tumor in the EU-4 and the UK

11.6

Japan

11.6.1

Total Incident Cases of GBM in Japan

11.6.2

Gender-specific Incidence Cases of GBM in Japan

11.6.3

Type-specific Incidence Cases of GBM in Japan

11.6.4

Age-specific Incidence Cases of GBM in Japan

11.6.5

Incident Cases based on Primary Site of GBM in Japan

11.6.6

Incident Cases based on Histologic Classification of GBM in Japan

12

Patient Journey

13

Key Endpoints in Glioblastoma Multiforme

14

Marketed Products

14.1

Key Competitors

15

Emerging Drugs

15.1

Key Competitors

16

GBM: Seven Major Market Analysis

16.1

Key Findings

16.2

Market Outlook

16.3

Key Market Forecast Assumptions

16.4

Attribute Analysis

16.5

Total Market Size of GBM in the 7MM

16.6

United States Market Size

16.6.1

Total Market size of GBM in the United States

16.6.2

Market Size of GBM by Current and Emerging Therapies in the United States

16.7

EU-4 and UK Market Size

16.7.1

Total Market size of GBM in the EU-4 and the UK

16.7.2

Market Size of GBM by Current and Emerging Therapies in the EU-4 and the UK

16.8

Japan Market Size

16.8.1

Total Market size of GBM in Japan

16.8.2

Market Size of GBM by Current and Emerging Therapies in Japan

17

KOL Views

18

Unmet Needs

19

Market Access and Reimbursement

19.1

United States

19.2

Europe

19.3

Japan

20

Appendix

20.1

Bibliography

20.2

Report Methodology

21

DelveInsight Capabilities

22

Disclaimer

23

About DelveInsight

Related Reports

Glioblastoma Multiforme Epidemiology Forecast

Glioblastoma Multiforme Epidemiology Forecast - 2032 report delivers an in-depth understanding of the disease, historical and forecasted glioblastoma multiforme epidemiology in the 7MM, i.e., the United States, EU-4 (Germany, Spain, Italy, and France), the United Kingdom, and Japan.

Glioblastoma Multiforme Pipeline

Glioblastoma Multiforme Pipeline Insight - 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key glioblastoma multiforme companies, including CNS Pharmaceutical, Pfizer, Roche, Autotelic Therapeutics, among others.

Recurrent Glioblastoma Market

Recurrent Glioblastoma Market Insights, Epidemiology, and Market Forecast - 2032 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key recurrent glioblastoma companies including Genenta Science, CNS Pharmaceutical, Pfizer, Roche, among others.

Recurrent Glioblastoma Pipeline

Recurrent Glioblastoma Pipeline Insight - 2022 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key recurrent glioblastoma companies, including Genenta Science, CNS Pharmaceutical, Pfizer, Roche, among others.

Recurrent Glioblastoma Epidemiology Forecast

Recurrent Glioblastoma Epidemiology Forecast - 2032 report delivers an in-depth understanding of the disease, historical, and forecasted recurrent glioblastoma epidemiology in the 7MM, i.e., the United States, EU-4 (Germany, Spain, Italy, and France), the United Kingdom, and Japan.

Other Trending Reports

Goitre Market | Thymus Cancer Market | US Healthcare Outlook Report | Venous Stenosis Market | Negative Pressure Wound Therapy Systems Market | Metrorrhagia Market | Dysfunctional Uterine Bleeding Market | Hypereosinophilic Syndrome Market | Age-related Vision Dysfunction Market | Dental Lasers Market | CRISPR Therapies Pipeline Insight | Cell And Gene Therapy For Multiple Myeloma Market | Drug Hypersensitivity Market | Dysthymia Market | Persistent Depressive Disorder Market | Cancer Vaccines Market | Weight Loss/Weight Management (Obesity) Market | Food Allergy Market | Obsessive-Compulsive Disorder Market | Tumor Ablation Market | Physiotherapy Equipment Market | CAR-T Pipeline Insight | Anti-hypertension Market | Radiofrequency Ablation Devices Market | Global Messenger RNA (mRNA)-based Vaccines and Therapeutics Market | Gastro Intestinal Bleeding Market | Trastuzumab Biosimilars Insight | Varicose Veins Market | Germ Cell Tumor Market | Intracardiac Echocardiography Devices Market | India Healthcare Outlook Report | Crows Feet Market Insight | Seborrhoeic Dermatitis Market | Injectable Drug Delivery Devices Market | Structural Heart Devices Market | Substance (Drug) Abuse Market

About DelveInsight

DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve.

Connect with us on LinkedIn|Facebook|Twitter

Additionally, get in touch with our business executive to explore @Healthcare Due Diligence Services

Contact Us

Shruti Thakur
info@delveinsight.com
+1(919)321-6187
www.delveinsight.com

Logo: https://mma.prnewswire.com/media/1082265/DelveInsight_Logo.jpg

Cision View original content:https://www.prnewswire.co.uk/news-releases/glioblastoma-multiforme-market-to-grow-significantly-at-a-cagr-of-13-1-during-the-forecast-period-20222032--delveinsight-301687839.html

© 2022 PR Newswire
Tech-Aktien mit Crash-Tendenzen
Künstliche Intelligenz, Magnificent Seven, Tech-Euphorie – seit Monaten scheint an der Börse nur eine Richtung zu existieren: nach oben. Doch hinter den Rekordkursen lauert eine gefährliche Wahrheit. Die Bewertungen vieler Tech-Schwergewichte haben historische Extremniveaus erreicht. Shiller-KGV bei 39, Buffett-Indikator auf Allzeithoch – schon in der Dotcom-Ära war der Markt kaum teurer.

Hinzu kommen euphorische Anlegerstimmung, IPO-Hypes ohne Substanz, kreditfinanzierte Wertpapierkäufe in Rekordhöhe und charttechnische Warnsignale, die Erinnerungen an 2000 und 2021 wecken. Gleichzeitig drücken geopolitische Risiken, Trumps aggressive Zollpolitik und saisonale Börsenschwäche auf die Perspektiven.

Die Gefahr: Aus der schleichenden Korrektur könnte ein rasanter Crash werden – und der könnte vor allem überbewertete KI- und Chipwerte hart treffen.

In unserem kostenlosen Spezial-Report zeigen wir Ihnen, welche Tech-Aktien am stärksten gefährdet sind und wie Sie Ihr Depot vor dem Platzen der Blase schützen könnten.

Holen Sie sich den neuesten Report!

Dieses exklusive Angebot gilt aber nur für kurze Zeit! Daher jetzt downloaden!
Werbehinweise: Die Billigung des Basisprospekts durch die BaFin ist nicht als ihre Befürwortung der angebotenen Wertpapiere zu verstehen. Wir empfehlen Interessenten und potenziellen Anlegern den Basisprospekt und die Endgültigen Bedingungen zu lesen, bevor sie eine Anlageentscheidung treffen, um sich möglichst umfassend zu informieren, insbesondere über die potenziellen Risiken und Chancen des Wertpapiers. Sie sind im Begriff, ein Produkt zu erwerben, das nicht einfach ist und schwer zu verstehen sein kann.