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“Imagine a burst of vibrant crimson and a delicate aroma that transports you to distant lands with each fragrant breath. Saffron, the ‘red gold’ of spices, has long been associated with exotic locales like Iran and Spain.
But what if I told you that you can cultivate this exquisite treasure right in your own backyard, amidst the rolling hills and moody skies of the United Kingdom?
In this journey of horticultural enchantment, we explore the intriguing question: Can you grow saffron in the UK? Prepare to unearth the secrets of this captivating endeavor, as we dive headfirst into the world of saffron cultivation in the heart of Britain.”
Can You Grow Saffron in the UK?
Yes, you can successfully grow saffron in the UK, although it requires specific conditions and careful attention to detail.
Exploring the Possibility:
Saffron, the prized spice derived from the delicate stigma of the Crocus sativus flower, is renowned for its rich flavor and vibrant color.
Traditionally associated with regions like Iran and Spain, one might wonder if it’s feasible to cultivate this precious spice in the UK’s less Mediterranean climate.
While the UK’s weather may not be as sun-drenched, the prospect of growing saffron on British soil is indeed attainable, provided you embrace the unique challenges and opportunities the climate presents.
Ideal Growing Conditions:
Saffron bulbs thrive in well-drained, sandy soil with good sunlight exposure. In the UK, regions with milder winters and plenty of sun, such as the South of England and parts of Wales, offer the most promising environments.
To safeguard against the colder months, planting saffron bulbs in raised beds or pots can provide the necessary insulation. Adequate moisture during the growing season is vital, but the bulbs should be kept relatively dry during dormancy.
Planting and Maintenance:
Planting saffron bulbs typically takes place in late summer or early autumn. It’s crucial to space the bulbs apart to allow for proper growth and avoid overcrowding.
Regular weeding and the removal of competing vegetation are essential to ensure the saffron flowers receive ample nutrients and sunlight.
Harvesting saffron stigmas, which are the spice-bearing parts of the flower, usually occurs in the autumn months, and meticulous attention to detail during this process is paramount to obtaining the highest-quality saffron.
Patience and Passion:
Growing saffron in the UK demands dedication, as the climate is not as naturally conducive as in traditional saffron-producing regions. with the right care and attention, you can cultivate this exquisite spice in your British garden.
The reward of harvesting your saffron threads, known for their culinary and medicinal value, is an experience that connects you to a centuries-old tradition, proving that saffron can indeed flourish even in the temperate embrace of the UK.
How to Grow Saffron In The UK?
|Prepare the Soil: Ensure the soil is well-draining and amended with organic matter to improve fertility and drainage. Saffron thrives in loose, sandy soil.
|Plant Saffron Corms: Plant saffron corms in late summer or early autumn, about 10-15 cm deep and 10-15 cm apart. Ensure the pointed end faces upwards. Water the corms thoroughly after planting.
|Provide Adequate Sunlight: Saffron requires plenty of sunlight. Choose a sunny location with at least 6-8 hours of direct sunlight per day. Consider using cloches or a greenhouse to extend the growing season.
|Maintain Proper Care: Regularly monitor soil moisture and ensure it doesn’t become waterlogged. During the growing season, water sparingly. Mulch the saffron bed to conserve moisture and suppress weeds.
|Harvest Saffron Threads: Saffron flowers typically bloom in autumn. Harvest the bright red stigmas (threads) with tweezers as soon as they open. Dry the threads immediately and store them in an airtight container.
Is saffron cultivation a profitable business?
Delving into the world of saffron farming reveals a fascinating opportunity for aspiring entrepreneurs. The allure of this crimson-hued spice, renowned for its luxurious aroma and culinary value, beckons many to explore its economic potential.
Saffron, derived from the Crocus sativus flower, is indeed one of the world’s most expensive spices by weight, making it a high-value crop.
Its profitability hinges on several factors, including climate, soil quality, and efficient farming practices.
Successful saffron cultivation demands meticulous attention to detail, but with the right conditions and dedication, it can yield lucrative returns. To maximize profitability, research and planning are key.
When to plant saffron crocus bulbs in the UK?
Timing is pivotal in saffron cultivation. In the UK, the ideal period to plant saffron crocus bulbs is in the early autumn, typically from late September to early October.
This timing aligns with the natural growth cycle of Crocus sativus, allowing the bulbs to establish roots before the winter frost sets in.
The relatively mild UK climate is suitable for saffron, and planting at the right time ensures the corms have adequate time to develop, resulting in robust flowering and saffron thread production come the following autumn.
Timing, therefore, is a crucial element in the journey to successful saffron cultivation in the UK, ultimately impacting both quality and potential profitability.
What is Saffron?
Saffron, often described as “red gold,” is a precious spice derived from the vivid crimson stigmas of Crocus sativus flowers.
These delicate threads are painstakingly harvested by hand, making saffron one of the world’s most expensive and sought-after spices.
Renowned for its distinct flavor, saffron imparts a “unique floral aroma” and “rich earthy taste” to dishes, making it a staple in cuisines such as Persian, Indian, and Spanish.
Historical Significance and Culinary Uses
Saffron’s history dates back millennia, with mentions in ancient texts and records. Its cultural significance and use as a natural dye and medicinal herb have contributed to its enduring legacy.
Culinary enthusiasts have marveled at its ability to “add depth and complexity” to dishes, from paella’s vibrant hue to biryani’s fragrant essence.
Its association with luxury and exclusivity has led to its presence in the most “sumptuous feasts” and “celebratory occasions” throughout history.
Saffron’s Cultivation Requirements
Saffron cultivation demands specific conditions for success. This includes a “Mediterranean climate” with dry summers and mild winters, well-draining “sandy loam soil,” and “full sun exposure.”
Adequate rainfall and temperature fluctuations are essential for the saffron crocus to thrive. Cultivating saffron also requires patience, as it can take several years for a saffron crocus bulb, known as a corm, to produce a significant harvest.
Saffron’s Ideal Growing Conditions
Climate and Weather Considerations:
- Saffron cultivation in the UK hinges on its temperate maritime climate, characterized by mild winters and moderate summers.
- Adequate rainfall during the growing season is crucial, but saffron doesn’t tolerate waterlogged soils.
Soil Requirements for Saffron:
- Well-draining, loamy soils are saffron’s preference, as they prevent corms from rotting.
- Saffron thrives in slightly alkaline soils with a pH range of 6 to 8.
Sunlight and Location Considerations:
- Choose a sunny location with at least 6 hours of direct sunlight daily for optimal saffron growth.
- Shelter saffron beds from strong winds that may damage the delicate flowers.
Watering and Drainage Needs:
- Saffron requires consistent moisture during its growing period, typically in autumn.
- Ensure efficient drainage to prevent waterlogged soil, which can harm the corms.
Challenges of Growing Saffron in the UK
UK’s Climate Challenges:
The temperamental British climate poses one of the foremost challenges when cultivating saffron.
The unpredictable weather patterns, marked by frequent rain and cool temperatures, can be detrimental to saffron’s delicate flowering and harvesting process. Saffron thrives in a dry, Mediterranean climate, making adaptation a necessity.
Pest and Disease Concerns:
Saffron crops in the UK are not immune to the threat of pests and diseases. Aphids, nematodes, and fungal infections can wreak havoc on saffron plants, requiring vigilant pest control and disease management strategies. This necessitates a proactive approach to safeguarding saffron fields.
Saffron demands well-draining, loamy soil with excellent aeration, a far cry from the heavy clay soils prevalent in parts of the UK.
Soil modification becomes crucial, as saffron’s corms and delicate root system require specific conditions to flourish. The need for soil adaptation adds complexity to the cultivation process.
Competing with Imported Saffron:
The availability of imported saffron from established saffron-producing regions like Iran and Spain can pose a challenge for UK saffron growers.
These foreign saffron varieties often dominate the market, making it challenging for UK saffron to establish a strong foothold, despite its unique appeal.
Steps to Grow Saffron in the UK
Soil Preparation and Amendment
Before embarking on your saffron-growing journey in the UK, it’s crucial to meticulously prepare your soil. Begin by selecting a well-draining, loamy soil with excellent aeration.
Many saffron growers in the UK recommend adding organic matter, such as compost or well-rotted manure, to enhance soil fertility and structure. This ensures that your saffron corms have the nutrient-rich environment they need to thrive.
Planting Saffron Corms
Planting saffron corms is a pivotal step in the process. Typically undertaken in late summer or early autumn, this involves placing the corms about 3-4 inches deep into the prepared soil, spaced at intervals of 4-6 inches.
It’s essential to position them with their pointed ends facing upwards to facilitate proper growth. Be sure to water them well after planting to settle the soil and initiate the growth process.
Managing Saffron During the Growing Season
Throughout the growing season, which spans from late autumn to early spring, diligent management is key.
Ensure your saffron bed receives adequate sunlight, as saffron thrives in sunny spots. Regular but moderate watering is essential to maintain soil moisture without waterlogging, and weed control is vital to prevent competition for resources.
Be prepared to protect your saffron from potential pests and diseases, particularly in the UK’s unpredictable climate.
Harvesting Saffron Threads
The exciting moment arrives when your saffron flowers bloom in late autumn. To harvest those precious crimson threads, carefully pluck the stigmas (the saffron threads) using tweezers or your fingers.
Exercise extreme caution to avoid damaging the delicate flowers. Timing is crucial, as saffron is most potent when freshly harvested. This labor-intensive process is rewarding, as it yields the prized saffron spice.
Once you’ve gathered your saffron threads, the post-harvest processing stage begins. To preserve saffron’s flavor and color, it’s advisable to dry the threads promptly.
Many UK saffron growers employ the traditional method of gently toasting the threads in a dry skillet or in the oven at a low temperature.
Afterward, store the dried saffron threads in an airtight container away from light and moisture. They can then be used to add exquisite flavor and aroma to your culinary creations.
Varieties of Saffron for UK Growth
Best saffron varieties for UK climate:
When considering growing saffron in the UK, selecting the right saffron variety is paramount.
The UK climate can be challenging, so opting for cold-hardy varieties such as Crocus sativus ‘Dutch’ or ‘Crocus sativus’ is advisable. These varieties have shown resilience to cooler temperatures, making them well-suited for British conditions.
Saffron color and flavor profiles:
Saffron enthusiasts often inquire about the distinct color and flavor profiles of different saffron varieties. The vibrant red threads of Crocus sativus ‘Cashmirianus’ are cherished for their potency and rich color.
In contrast, ‘Spanish Superior’ saffron boasts a more mellow, earthy flavor. Understanding these profiles can help you choose the saffron that aligns best with your culinary preferences.
Where to source saffron corms in the UK:
Locating high-quality saffron corms in the UK can be a challenge, but it’s essential for successful cultivation. Many garden centers and online suppliers offer saffron corms suitable for the UK climate.
Look for reputable sources with a track record of providing healthy and viable corms to kickstart your saffron-growing venture.
Success Stories and Testimonials
Interviews with UK Saffron Growers
In-depth conversations with seasoned UK saffron cultivators shed light on their inspiring journeys.
These passionate individuals, often described as “saffron pioneers” or “local saffron heroes,” generously shared their experiences and insights, offering a rare glimpse into the world of saffron farming in the UK.
Challenges They Faced and How They Overcame Them
These tenacious saffron enthusiasts faced a myriad of challenges, from the unpredictable British weather to soil adaptation hurdles. Yet, their resourcefulness and determination led them to innovative solutions, earning them accolades like “saffron problem-solvers” and “resilient saffron champions.”
Tips and Advice for Prospective Saffron Growers
For those aspiring to cultivate saffron in the UK, these seasoned growers offer invaluable pearls of wisdom. Their sage advice includes tips on “UK saffron best practices,” “maximizing saffron yields,” and “saffron cultivation secrets.”
Their guidance is like a treasure trove for anyone looking to embark on their saffron-growing journey in the United Kingdom.
Potential Benefits of Growing Saffron in the UK
Saffron cultivation in the UK holds substantial economic promise, offering a lucrative opportunity for farmers and entrepreneurs.
With a growing demand for high-quality saffron in the culinary and medicinal industries, locally produced saffron can tap into a profitable market. This endeavor can stimulate rural economies, create jobs, and boost income for growers.
Embracing saffron cultivation in the UK carries significant environmental advantages. Saffron, a natural perennial plant, requires less water compared to many other crops, reducing the strain on local water resources.
Moreover, saffron fields support biodiversity by attracting pollinators, enhancing the overall ecological balance, and fostering a sustainable farming ecosystem.
Promoting Local and Sustainable Saffron Production:
Cultivating saffron locally promotes sustainable agriculture practices, reducing the carbon footprint associated with long-distance saffron imports.
It empowers local farmers, contributing to food security and reducing reliance on foreign sources. Consumers also benefit from fresher, more transparent sourcing, aligning with the growing preference for locally grown and sustainable products.
Suitable Cities for Saffron Growing
Saffron cultivation in England has seen a resurgence in recent years, with several cities proving to be suitable for this delicate spice’s growth. Let’s explore four notable regions:
Saffron in Essex:
Essex Saffron, known for its vibrant crimson threads, has garnered attention. The county’s well-draining soil and relatively mild climate create favorable conditions for saffron cultivation.
Essex saffron farms are becoming increasingly popular, offering a local and sustainable source of this precious spice.
Devon, with its rich, loamy soils and moderate temperatures, provides an ideal environment for saffron to flourish.
Devon saffron growers have been reviving the tradition of cultivating this valuable crop, contributing to the region’s agricultural diversity.
The Norfolk countryside boasts a picturesque setting for saffron cultivation, with its well-drained sandy soils and plenty of sunlight.
Norfolk saffron production has gained recognition for its high-quality saffron threads, catering to both local demand and wider markets.
Saffron at Croydon:
Even within the bustling metropolis, there are urban saffron enthusiasts. Saffron in Croydon represents a unique blend of urban farming and traditional spice cultivation.
Croydon saffron projects highlight the adaptability of saffron cultivation, even in city environments.
FAQ: Can You Grow Saffron in the UK?
Can saffron be successfully grown in the United Kingdom?
Yes, it is possible to grow saffron in the UK, although it comes with specific challenges due to the climate.
What is saffron, and why is it challenging to grow in the UK?
Saffron is a spice derived from the flower of Crocus sativus. It’s challenging to grow in the UK because saffron requires a dry, warm climate, and the UK generally has a cool, wet climate.
Which regions in the UK are best suited for saffron cultivation?
The best regions for saffron cultivation in the UK are those with milder winters and well-draining soil, such as parts of Cornwall, Devon, and East Anglia.
Can saffron bulbs survive the cold UK winters?
Saffron bulbs can survive UK winters, but they need protection. Planting them in well-draining soil and mulching can help insulate them from harsh winter conditions.
When is the best time to plant saffron bulbs in the UK?
Saffron bulbs are typically planted in the UK between late summer and early autumn. This gives them time to establish roots before winter.
How do I care for saffron plants in the UK?
Saffron plants require well-draining soil, adequate sunlight, and regular watering during the growing season. They should be lifted and divided every few years.
Can saffron be grown indoors or in greenhouses in the UK?
Yes, saffron can be grown indoors or in greenhouses in the UK to provide a more controlled environment, especially in regions with colder winters.
How long does it take for saffron flowers to bloom in the UK?
Saffron flowers typically bloom in the UK in late autumn. Each flower only blooms for a short period, usually just one day.
Can I harvest saffron in the UK, and when is the best time to do it?
Yes, you can harvest saffron in the UK. The best time to harvest is in the morning when the flowers have just opened. This usually occurs during October.
Is it economically viable to grow saffron in the UK for commercial purposes?
Commercial saffron cultivation in the UK can be challenging due to the labor-intensive nature of harvesting and the limited yield per flower. It’s more commonly grown on a small scale or as a specialty crop.
In conclusion, the possibility of growing saffron in the UK is indeed achievable, albeit with some challenges.
While the UK’s climate may not be ideal for saffron cultivation, with its relatively milder winters and frequent rainfall, innovative techniques such as planting saffron corms in well-drained soil, using protective structures like polytunnels, and providing the necessary care and attention can help saffron enthusiasts yield a successful crop.
The pursuit of cultivating this precious spice in the UK not only offers a unique horticultural challenge but also contributes to the local economy and encourages sustainable agriculture practices.
With the right knowledge and dedication, individuals and farmers can enjoy the delight of growing their own saffron and savoring its exquisite flavor and aroma.
So, while it may not be without its obstacles, the dream of cultivating saffron in the UK is a pursuit worth exploring for those passionate about this remarkable spice.


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Prototype creation is a key part of the product development effort that design engineers use to allow them to explore design alternatives, test theories and confirm performance prior to starting production of a new product. Solid’s talented engineers use their experience to tailor the prototype according to the specific unknowns still present in the intended design. A series of prototypes will often be constructed and tested as the final design emerges and is prepared for production. With rare exceptions, multiple iterations of prototypes are used to progressively refine the design. Solid’s strategy in developing your product is design, test, evaluate and then modify the design based on analysis of the prototypes.
In addition, to prototyping for testing and design validation, Solid will generate product mock-ups for early stage conceptualization. Combined with other Industrial Design techniques, Solid strives to achieve a complete understanding of user centric attributes for every product. Product modeling provides Solid designers first-hand knowledge of environmental features and product feel. This early stage process is a low cost method to apply a unique look and form to products to ensure they will align with end-user interests.
Prototypes, product mock-ups and short run components are created quickly using state of the art machines both manual and CNC such as our Milltronics CNC Vertical Machining Center. Please stop in for a tour of our facility.

domain: design


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Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial
Trials volume 21, Article number: 352 (2020)
Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group.
This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or “frail” (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1).
Patients are stratified according to modified Cancer and Age Research Group (CARG) score: “fit” patients are allocated to combination CT (carboplatin/nab-paclitaxel) and “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks.
The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers.
The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.
ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017.
Eudra-CT, 2016–003963-20; initially registered on 3 January 2017.
Lung cancer is one of the most commonly diagnosed cancer types and the leading cause of cancer death worldwide . It is predominantly a disease of the elderly, with about 50% of patients diagnosed aged 70 years or older . Age is an independent prognostic factor affecting survival in this group of patients .
Metastatic non-small cell lung cancer (NSCLC) carries a dismal prognosis with a median survival of less than 12 months . Systemic treatment, such as mono-chemotherapy (e.g., vinorelbine or gemcitabine) [5, 6] or a dose-adapted combination of carboplatin (area under the curve (AUC) 6)/paclitaxel (90 mg/m2; d1 + 8 + 15) , is considered to improve outcomes in patients who are aged ≥ 70 years, are frail, or have a reduced performance score (i.e., Eastern Cooperative Oncology Group (ECOG) ≥ 2).
The use of geriatric assessment and screening tools is recommended in elderly patients to better adapt intensity of treatment to patient condition and comorbidities . As a complex geriatric assessment (CGA) is time- and resource-consuming and potentially not required for all patients, shorter pre-therapy risk assessments have been developed, i.e., the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients)  and the CARG (Cancer and Age Research Group)  scores.
While the CRASH score contains variables for clinical and geriatric assessment, the CARG score comprises geriatric assessment questions and clinical questions concerning items retrieved from everyday practice. Both scores are considered as useful toxicity prediction tools, appropriate for implementation in routine clinical practice, with a potential impact on the optimization of therapy selection for elderly patients with cancer .
With the advent of immune-oncology, new options have become available. Currently, checkpoint inhibition therapies targeting PD-1 and PD-L1 are established as first-line treatment in metastatic lung cancer. This is based on several impressive efficacy results of anti-PD-1/PD-L1 antibodies in clinical trials in NSCLC that have led to the approval of nivolumab, pembrolizumab, and atezolizumab [12,13,14,15] first in advanced therapy lines and later in the first-line setting (mono-immunotherapy for PD-L1 ≥ 50% or regardless of PD-L1 tumor expression in combination with a combination chemotherapy) [16, 17]. However, clinical evidence about the tolerability and safety of checkpoint inhibition as a treatment option in frail and elderly patients is still lacking.
In addition, it remains an unresolved question whether efficacy of checkpoint inhibitors in older patients is affected by a still poorly characterized phenomenon referred to as immunosenescence, i.e., the global and progressive remodeling of immune functions with aging [14, 15, 18, 19]. Age-related alterations such as impaired T-cell activation, reduced T-cell receptor diversity, altered antigen-uptake and -presenting functions, or the increased generation of immune suppressive cells may impair the antitumor response and thus could be one of the reasons for a higher incidence and prevalence of most cancers in older people.
Furthermore, a paradoxical stimulation of tumor growth upon initiation of treatment with checkpoint inhibitors, so-called hyperprogressive disease, has been reported in a recent retrospective analysis in up to 19% of patients older than 65 years. This could potentially be caused by an altered immune function due to immunosenescence .
In conclusion, with the increasing use of immunotherapy in everyday clinical practice there is a growing interest in immunosenescence and how it may correlate with outcomes of immunotherapy in elderly patients [18, 21]. However, data derived from randomized trials investigating safety and tolerability of checkpoint inhibitors in this specific population of lung cancer patients are lacking.
The DURATION study is an open label, treatment-stratified, and randomized phase II study (Fig. 1) enrolling patients with histologically confirmed NSCLC (adenocarcinoma and squamous) stage four (metastatic) prior to any systemic treatment. All procedures and time frames displayed in Fig. 1 and the schedule of assessment (Table 3) were developed according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT). Additional file 1 contains the complete SPIRIT checklist.
The DURATION trial is a multicenter trial, recruiting patients from approximately 30 sites across Germany. A full list of sites can be obtained at ClinicalTrials.gov (NCT03345810).
The primary objective is to investigate the safety and tolerability of sequential therapy consisting of standard of care single agent or doublet chemotherapy followed by durvalumab in comparison to standard of care single-agent or doublet chemotherapy in frail and/or elderly patients.
Secondary objectives are to collect information on efficacy, safety, and quality of life parameters and to investigate the utility of geriatric assessments for treatment guidance. Geriatric assessment and quality of life parameters will be collected before and at distinct time points during the treatment course.
Exploratory objectives are to identify potential predictive biomarkers for efficacy variables. To this end, tissue collection and blood sampling will be performed before and during the course of disease/treatment. The blood and tissue samples will be subjected to molecular analyses to search for markers of immune response in this population.
Analysis of biomarker data will include correlations with clinical phenotype and tumor PD-L1 expression.
Characteristics of patients
Two-hundred frail and/or elderly patients with metastatic NSCLC with no targetable molecular alterations (EGFRwt, EML4ALKtransl-) before first-line treatment will be included.
Key inclusion criteria are age ≥ 70 years and/or Charlson Comorbidity Index (CCI) > 1 and/or ECOG > 1, previously untreated NSCLC with no targetable molecular alterations (EGFRwt, EML4ALKtransl-), and the availability of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block (fresh or archival less than 3 years old or recent) or a minimum of ten unstained slides of tumor sample for biomarker (PD-L1) evaluation. Key exclusion criteria include mixed small cell lung cancer with NSCLC and large-cell lung carcinoma histology and history of another primary active malignancy or active autoimmune disease.
For a full list of inclusion and exclusion criteria see Table 1.
Procedures for stratification
Total risk score ≤ 3 → doublet chemotherapy
Total risk score > 3 → single-agent chemotherapy
The aim is to prevent > 50% of standard chemotherapy toxicities (CTCAE grade III/IV). The risk score will be determined according to Table 2.
The subjects must first read, understand, and sign the approved informed consent form (ICF) before any study-specific screening procedures are performed. After signing the ICF, completing all screening procedures, and being deemed eligible for entry, subjects will be enrolled in the study. Procedures that are performed prior to the signing of the ICF and are considered standard of care may be used as screening assessments if they fall within the 28-day screening window (in particular tumor stagings).
After the stratification procedure (modified CARG score) done by the investigator, the investigator will access the randomization website to assign the participant to the treatment arms. Randomization is performed using permuted block randomization with fixed block lengths. Treatment arm allocation (ratio 1:1) will be done following the Standard Operational Procedures of the Institut für Klinische Forschung (IKF, Frankfurt Germany), which is the clinical research organization of the DURATION trial (CRO). After randomization the system will immediately confirm a patient’s allocation to the treatment arms, to receive either four cycles of single agent or doublet chemotherapy or two cycles of single-agent or doublet chemotherapy followed by two cycles of immunotherapy. After four cycles of standard chemotherapy, patients receive either follow-up care (arm A and D) or a maintenance therapy with durvalumab for a maximum of 2 years in the experimental arms B and C. Dose modification and toxicity management are described in detail in the “Treatment plan” section of the protocol. Furthermore, detailed information about permitted or prohibited concomitant treatment can be obtained from the protocol.
Subject adherence to protocol interventions
No particular methods to improve adherence to trial intervention have been implemented. Due to the nature of the disease under study (advanced or metastatic lung cancer), patients are naturally motivated to adhere to the trial intervention. Furthermore, the trial medication is not self-administered by the study subjects but rather investigator administered according to a pre-specified visiting calendar of the trial protocol.
Strategies to achieve target sample size
The DURATION trial was set-up with the clinical trial network of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Each of the 30 participating sites was selected by the sponsor based on former and anticipated accrual performance. The accrual rate is monitored on a monthly basis and any shortfall communicated to the CI and the sponsor. Regular newsletters and meetings within the trial network are routine tools to maintain a steady accrual rate. Based on the discretion of the sponsor, additional study sites may be included to bolster recruitment.
For each patient enrolled, an electronic case report form (eCRF) must be completed by the principal investigator or authorized delegate from the study staff. This also applies to records for those patients who fail to complete the study. If a patient withdraws from the study, the reason must be noted in the eCRF. Subjects who are permanently discontinued from the study medication will be followed for safety unless consent is withdrawn or the subject is lost to follow-up or enrolled in another clinical study. All subjects will be followed for survival. Subjects who decline to return to the site for evaluations will be offered follow-up by phone as an alternative.
Treatment emergent adverse events (AEs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 will be recorded in the eCRF using a recognized medical term or diagnosis that accurately reflects the event. AEs will be assessed by the investigator for severity, relationship to the investigational product, possible etiologies, and whether the event meets criteria of a serious adverse event (SAE) and therefore requires immediate notification to the CRO. AEs and SAEs will be recorded during the entire study duration, including the regular 30-day safety follow-up period after the end-of-treatment (EOT) visit. Subsequently, subjects will be followed for ongoing study treatment-related AEs until resolved, return to baseline, or deemed irreversible, until lost to follow-up, or withdrawal of study consent. Non-SAEs are recorded from time of signed informed consent until 30 days after the last dose of the investigational medicinal product (IMP). SAEs are recorded from time of signed informed consent until 90 days after the last dose of IMP. AEs of special interest (non-serious and serious AESI) are recorded from time of signed informed consent until 90 days after last dose of IMP. The investigator is responsible for ensuring that all AEs observed by the investigator or reported by patients are properly captured in the patients’ medical records. During the course of the study all AEs and SAEs should be proactively followed up for each subject. Every effort should be made to obtain a resolution for all events, even if the events continue after discontinuation/study completion.
A data safety monitoring board (DSMB) will monitor trial conduct. The primary objective of the DSMB is to monitor the safety of the intervention of the clinical study according to the protocol. The DSMB will evaluate the safety of the study intervention and will propose changes, termination, or continuation of the trial to the sponsor and the coordinating investigator. It will consist of two experienced thoracic oncologists. The first interim safety assessment will be conducted after the first 20 subjects have been treated with at least two cycles of durvalumab. Thereafter, yearly assessments, synchronized with the annual safety reports, will be performed. Details are provided in the protocol referring to the DSMB Charter.
The CRO must provide a trained monitor to assist the investigators in conducting the clinical study. The monitor has the responsibility of reviewing the ongoing study with the investigators to verify adherence to the protocol and to deal with any problems that arise. The study monitor will review the eCRF data for completeness and accuracy during the monitoring visits. The study monitor will point out any discrepancies between source data and the data captured in the eCRF. The monitor will issue electronic queries to site staff to initiate discrepancy resolution. Discrepancies which require eCRF data corrections have to be re-solved by authorized site personnel by answering these monitoring queries. The frequency of on-site visits will depend on the number of recruited patients and results of prior monitoring (risk-adapted monitoring). The monitor must be given access to subjects’ medical records and other study-related records needed to verify the entries in the eCRF. The investigator agrees to cooperate with the monitor to ensure that any problems detected in the course of these monitoring visits, including delays in completing case report forms, are resolved. The investigator has to ensure that all data required according to this protocol will be entered promptly in the eCRF.
Collection of safety data/harms
It is the responsibility of the investigators to document all AEs occurring during the study in the patients’ medical files and eCRFs. Any SAE or AE of special interest, overdose of IMP, and pregnancies must be reported immediately (within 24 h) to the sponsor. The sponsor and the CRO will ensure compliance with all regulatory reporting requirements, including the notification of the appropriate Ethics Committees, Competent Authority, and participating investigators of all SAEs occurring at the sites in accordance with national law, ICH Good Clinical Practice, and European/EMA requirements.
A sponsor representative (e.g., CRO) will medically review all SAE reports and perform the expectedness assessment.
Every SAE assessed by either the investigator or the sponsor as suspected to be related to IMP and assessed as being either unexpected or unexpected with regard to outcome or severity of the event will be reported by the sponsor as suspected unexpected serious adverse reaction (SUSAR) to the competent authority, responsible ethics committee, and investigators of the trial in line with the national regulations in effect (German drug law [AMG] and GCP-V § 13).
Data management and data quality assurance
Accurate and reliable data collection will be assured by verification and cross–check of the eCRF against the investigator’s records by the study monitor (source document verification), and the maintenance of a drug-dispensing log by the investigator. Data for this study will be recorded via eCRF by the site from the source documents. Data are reviewed and checked for omissions, apparent errors, and values requiring further clarifications using computerized (automatic) and/or manual procedures. Data queries requiring clarification are communicated to the site for resolution via the CRO. Only authorized personnel will make corrections to the clinical database and an audit trail will document all corrections.
Protocol amendments are submitted to the competent authorities and ethics committees for approval according to local legislation. Only after regulatory approval changes to the protocol are communicated to all sites via mail or newsletter. Important safety information (e.g., SUSARS) are communicated directly to the participating investigator in parallel to reporting such information to the competent authorities.
An overview of all study procedures is presented in Table 3.
Treatment arms A and D: standard of care single agent or doublet chemotherapy
Arm A: nab-paclitaxel 100 mg/m2 on days d1 and d8 and carboplatin AUC 5 on day 1, every 3 weeks up to four cycles.
Arm D: gemcitabine 1000 mg/m2 on days d1 and d8, given every 3 weeks, or vinorelbine 30 mg/m2 on days d1 and d8 every 3 weeks up to four cycles.
Treatment arms B and C: two cycles of single agent or doublet chemotherapy followed by durvalumab
Arm B: two cycles of nab-paclitaxel 100 mg/m2 on days d1 and d8 and carboplatin AUC 5 on day 1, every 3 weeks followed by durvalumab 1125 mg every 3 weeks for two cycles followed by maintenance with durvalumab 1500 mg every 4 weeks.
Arm C: two cycles of gemcitabine 1000 mg/m2 on days d1 and d8, given every 3 weeks or vinorelbine 30 mg/m2 on days d1 and d8 every 3 weeks up to four cycles followed by durvalumab 1125 mg every 3 weeks for two cycles followed by maintenance with durvalumab 1500 mg every 4 weeks.
Tissue and blood collection for exploratory endpoints
For each patient a FFPE tumor tissue block (archival or recent) or a minimum of ten unstained slides of tumor sample (2–3-μm sections; slices must be recent and collected on slides provided by the sponsor) must be available for biomarker (PD-L1) evaluation as stated in the inclusion criteria. Biopsy should be excisional, incisional, or core-needle. Fine-needle aspiration is insufficient. Tumor PD-L1 expression is measured by an immunohistochemistry assay using SP263 antibody. If a re-biopsy upon tumor progression under study treatment is performed, submission of this tumor material is highly valued.
Participation of patients in the biomarker program is voluntary and must be documented in the informed consent form. The time points for blood sampling are before start of any treatment at baseline and after two cycles of chemotherapy, as well as after 20 weeks of study participation for all patients with stable disease or tumor regression and at the time point of detection of tumor growth in patients with disease progression. In arms B and C, blood is additionally collected after the first cycle of durvalumab.
The primary endpoint is the rate of treatment-related grade III/IV adverse events (CTCAE V4.03). It will be calculated taking into account patients who have received at least one dose of study medication.
Secondary endpoints will be:
Overall response rate (ORR) according to RECIST 1.1 criteria
Progression-free survival (PFS), calculated from the date of subject randomization until the date of confirmed PD or death from any cause; if no event is observed (e.g., lost to follow-up) PFS is censored at the time of last tumor assessment
Overall survival (OS) will be calculated from the date of subject randomization until the date of death from any cause; if no event is observed (e.g., lost to follow-up), OS is censored at the day of last subject contact
AEs/SAEs according to CTCAE 4.03
Health-related quality of life (HR-QoL) assessment using Functional Assessment of Cancer Therapy–Lung (FACT-L) questionnaire, a standard instrument to determine QoL including lung-specific domains
Exploratory analysis on tissue samples
Patients will provide a tumor tissue sample at screening to determine PD-L1 expression level. This assessment will be centralized and performed by an immunohistochemistry assay using SP263 antibody. The results will be used to correlate PD-L1 staining intensity (proportion of positive tumor and immune cells) with durvalumab efficacy.
Exploratory analysis on blood samples
Blood samples that are collected at different time points will be used to characterize the immune response and investigate biological processes before, during, and after the administration of the treatment. Flow cytometric (FCM) analysis will be used to characterize the immune response and the biological processes before, during, and after the administration of the treatment. Whole blood samples will be analyzed with this modality with respect to changes in T-cell composition. Abundances of immunostimulatory cytokines will be quantified by measuring serum pro- and anti-inflammatory cytokines. Analysis of mutational load on cfDNA will be performed.
The primary safety endpoint for the study is the occurrence of CTCAE grade III/IV toxicities assessed from the first dose to 90 days after the last dose of durvalumab. This is also the primary study endpoint on which the sample size calculation is based. According to the results presented at ASCO 2015 by Rizvi et al., it is assumed that the probability for a CTC grade III/IV toxicity for patients from the pooled experimental arms B + C receiving durvalumab amounts to PB + C = 0.18 . Based on reported data of selected treatment-related AEs (combination chemotherapy nab-paclitaxel/carboplatin , mono-chemotherapy gemcitabine/vinorelbine ), it is furthermore assumed that the rate of patients with a CTC grade III/IV toxicity in the pooled control arms A + D receiving chemotherapy only amounts to PA + D = 0.35. With the planned number of patients of N = 200, the assumed difference between these two groups can be detected using a Chi-square test at a two-sided significance level of α = 10% with a probability of 1 − β = 0.80, also taking into account a dropout rate of 15%. Sample size calculation was performed using ADDPLAN v6.1.
It should be noted that the study is not powered to detect significant differences with regard to the efficacy endpoints, since its primary aim is to assess safety and tolerability. Hence, no confirmatory evidence can be drawn from the efficacy evaluation. Accordingly, all p values for efficacy outcomes are only to be interpreted descriptively and no adjustment for multiple testing will be done.
The null hypothesis for the primary (safety) endpoint of the trial is defined as H0: PB + C = PA + D (i.e., the rate of patients with a CTC grade III/IV toxicity is equal in the pooled experimental arms B + C and the pooled control arms A + D), which is tested against its alternative H1: PB + C ≠ PA + D (i.e., there is a difference between the pooled experimental arms B + C and the pooled control arms A + D with regard to the rate of patients with a CTC grade III/IV toxicity). These hypotheses will be assessed at a two-sided significance level of α = 0.1 using a Mantel-Haenszel Chi-square test adjusting for the stratum “adopted combination/not prone to combination”. Missing data for the primary outcome variable will be replaced by using multiple imputation . The analysis of the primary endpoint will be based on the safety population comprising all patients enrolled who received at least one dose of study medication. Secondary endpoints will be analyzed descriptively. The analysis of PFS will be performed analogously to the analysis of OS by calculating 1-year and 2-year rates and median times per group, conducting a stratified log rank test, calculating Kaplan Meier curves, and estimating the hazard ratio using a Cox regression adjusting for the stratum “adopted combination/not prone to combination”. Other secondary endpoints will be analyzed descriptively by tabulating the measures of the empirical distributions. Subgroup analyses according to PD-L1 expression will be performed. A detailed methodology for the statistical analysis will be described in the statistical analysis plan (SAP), which will be finalized before data base lock. Statistical analysis will be done using SAS v9.4 or higher (SAS Institute, Cary, NC, USA).
Lung cancer is the most common cause of cancer-related death worldwide and it is predominantly a disease of the elderly, with about 50% of patients diagnosed aged 70 years or older and with about 14% of these being older than 80 years . Due to the fact that lung cancer is mostly diagnosed at an advanced stage, prognosis is very poor.
Chemotherapy is effective in elderly NSCLC patients. However, they might experience treatment toxicity and deterioration due to side effects. The Elderly Selection on Geriatric Index Assessment (ESOGIA) trial was the first prospective study to investigate comprehensive geriatric assessment (CGA) incorporation into cancer treatment decisions and its impact on survival outcomes . The study randomly assigned 192 stage IV NSCLC patients with a median age of 77 years to a standard arm or a CGA arm, where patients received either one of two chemotherapy regimens or best supportive care (BSC) based on performance status (PS) and age or on the CGA evaluation, respectively. Importantly, the treatment allocation based on CGA reduced treatment toxicities and the number of toxicity-related treatment failures, although it was not able to improve treatment failure-free survival or OS. This trial for the first time demonstrated the feasibility of incorporating CGA in a multicenter clinical trial setting and that CGA-based treatment is associated with decreased toxicity in elderly NSCLC patients. In clinical practice, however, the implementation of CGA has been difficult because it is rather time- and resource-consuming. Consequently, alternative pre-therapy risk assessment tools have been developed to predict chemotherapy toxicity, the CRASH and CARG scores being the two most promising tools for assigning patients to varying chemotherapy intensities based on pre-therapy risk assessment.
In the DURATION trial, the CARG toxicity prediction tool will be used to guide treatment intensity with the intention to improve outcomes of elderly and frail patients. The CARG score has been developed to stratify patients and identify those at higher risk for chemotherapy toxicity . It consists of 11 questions, including five geriatric assessment questions and six clinical questions concerning items retrieved from everyday practice. The CARG score was validated in lung cancer, showing its value in better distinguishing the risks of chemotherapy toxicity in older patients compared to the Karnofsky performance status (KPS) . Its value in treating and predicting mortality in elderly patients with cancer is now broadly accepted. Minor modifications of the CARG score in the DURATION trial include the removal of the default scoring items “polychemotherapy” and standard dose as well as the items “GI” or “GU cancer”, which do not apply to this study. The predictive properties of the CARG score remain unchanged.
According to this modified CARG toxicity tool, patients in the DURATION trial will be classified as “fit” or as “less fit” with regard to receiving a platinum-based combination chemotherapy. “Less fit” patients will be treated with a single-agent chemotherapy of either vinorelbine or gemcitabine. Both single-agent chemotherapy regimens were established as the standard of care over best supportive care for first-line therapy of advanced NSCLC patients aged 70 years or older [5, 29]. Patients that are stratified as fit will receive treatment according to current ESMO guidelines for advanced NSCLC that recommend platinum-based combination chemotherapy for patients aged > 70 years with PS 0–2 and adequate organ function based on a recent systematic review . The combination chemotherapy applied in the DURATION trial consists of a combination of nab-paclitaxel with carboplatin as inferred from clinical trials and retrospective analyses that demonstrated superiority of carboplatin/nab-paclitaxel over carboplatin/paclitaxel with respect to efficacy and safety in elderly patients [25, 31]. Both patient groups treated with either single-agent or doublet chemotherapy will be subjected to randomization for treatment with the PD-L1 inhibitor durvalumab.
Based on promising results from clinical trials, immuno-oncology agents such as PD-1 - or PD-L1 inhibitors have found their way into frequent clinical use, even in the first-line setting, and have revolutionized the treatment landscape of NSCLC . However, due to underrepresentation of older patients in large trials that led to approval of checkpoint inhibitors, all available efficacy and safety data for this patient group is derived from subgroup analyses. Such analyses of second-line trials revealed no differences in response rates and survival between patients aged less or more than 65 years [12, 14, 18, 33, 34] . Similarly, KEYNOTE-024, a first-line clinical trial comparing pembrolizumab with combination chemotherapy in advanced NSCLC patients with PD-L1 expression > 50%, indicated no differences in the beneficial effect of pembrolizumab when comparing patients aged < 65 years and > 65 years) . Of note, no differences regarding toxicities between age groups were observed . However, to date no data from randomized phase III trials assessing the efficacy of PD-1/PD-L1 targeting agents in elderly patients with advanced NSCLC are available.
In addition, addressing immuno-oncology agents specifically in older patients is of particular interest as a phenomenon called immunosenescence has to be considered. This age-related decline in the immune system includes reductions in B- and T-cell proliferation and function, quantitative differences in cellular subsets, functional impairment, and qualitative changes in APCs and an accumulation of regulatory T cells—processes that eventually could be associated with impaired immune response to pathogens and tumor cells .
Considering the growing number of immune checkpoint inhibitors that are available for the treatment of NSCLC patients, it is also important to learn about potential differences between PD-1- and PD-L1- targeting agents. Although each drug has shown activity in NSCLC, comparing these agents in terms of efficacy and toxicity is the subject of current research. A recent systematic review of clinical trials that tested both PD-1 and PD-L1 antibodies did not find significant differences between the two types of checkpoint inhibitors regarding the reported response rates and toxicity profiles . The most notable difference was observed regarding grade III/IV immune-mediated pneumonitis that was slightly higher with PD-1 inhibitors compared with PD-L1 inhibitors. This could possibly be explained by the fact that anti-PD-L1 antibodies still allow for the interaction of PD-1 with its other ligand, PD-L2, thus resulting in a weaker blockade of the negative inhibitory signal and reduced autoimmunity . The development of autoimmune pneumonitis has to be carefully monitored in NSCLC patients as this has led to a few treatment-related deaths in early-phase studies of PD-1-targeting agents [13, 36, 37] and patients with lung cancer are more vulnerable to toxicities given the older age of the patient population and the presence of comorbid conditions. Given the putatively lower risk of developing autoimmune-mediated toxicities with PD-L1 targeting agents, the use of durvalumab, a selective, high-affinity, human IgG1 monoclonal anti-PD-L1 antibody [38,39,40], is expected to be more suitable for treatment of a more vulnerable patient group such as old or frail NSCLC patients that are included in the DURATION trial. Encouraging antitumor activity of durvalumab has already been shown in an early-phase clinical study involving multiple advanced solid tumors, including NSCLC, and recently it has been approved for patients with locally advanced NSCLC after chemoradiotherapy [38, 41].
In the DURATION trial, checkpoint inhibition by durvalumab is combined sequentially with cytotoxic chemotherapy. It is thought that modulation of the immune response through PD-1 inhibition may be enhanced by the potential immunogenic effects of cytotoxic chemotherapy, e.g., by increasing the potential for antigen cross-presentation by dendritic cells after the destruction of tumor cells, inhibiting myeloid-derived suppressor cells, increasing the ratio of cytotoxic lymphocytes to regulatory T cells, and blocking the STAT6 pathway to enhance dendritic-cell activity [42,43,44,45]. Thus, the two cycles of induction chemotherapy that are applied in the DURATION trial are expected to lead to a prompt disease-stabilizing effect, which can be efficaciously extended by a consecutive PD-L1 immunotherapy with durvalumab.
Current treatment guidelines recommend the use of immunotherapy alone or in combination with CT also for older lung cancer patients with adequate PS ECOG . Considering the underrepresentation of older and frail patients in main pivotal trials that led to the approval of these new treatment modalities, there’s a lack of data about safety and efficacy in this group. Aging processes, comorbidities, and undetected frailty could affect treatment tolerance in the face of a poor clinical benefit. The DURATION trial will help to close the current gap in knowledge about safety and tolerability of checkpoint inhibitors in elderly and frail lung cancer patients, an important cohort that has been underrepresented in clinical trials for too long.
Patient accrual started in December 2017 with protocol version 5.0 and is currently ongoing according to the protocol version number 7. Two amendments were necessary, due to annual updated IB of Durvalumab, leading to protocol version 6.0 (approval 24.05.2018) and version 7.0 (approval 27.06.2019). At present, 30 centers are participating in this study. The approximate end of recruitment will be in December 2020.
Availability of data and materials
Not applicable as no primary data are contained, generated, or analyzed.
Arbeitsgemeinschaft Internistische Onkologie
Antigen presenting cells
American Society of Clinical Oncology
Area under the curve
Best supportive care
Cancer and aging research group
Charlson Comorbidity Index
Cluster of differentiation
Cell-free deoxyribose nucleic acid
Comprehensive geriatric assessment
Chemotherapy Risk Assessment Scale for High-Age Patients
Common Terminology Criteria for Adverse Events
Eastern Cooperative Oncology Group
Epidermal growth factor receptor
Echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase
European Society for Medical Oncology
Fluorescence activated cell sorter
Hepatitis B virus
Hepatitis C virus
Health related quality of life
Investigational medical product
Immune-related response evaluation criteria in solid tumors
Magnetic resonance imaging
Six-minute walk test
Non-small cell lung cancer
Objective response rate
Programmed death-ligand 1
Response evaluation criteria in solid tumors
Severe adverse event
Quality of life
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The authors would like to thank the members of the Protocol Board and the Data Safety and Monitoring Board. They would also like to thank Inn Chung for comments on the manuscript.
This trial is conducted by the Young Medical Oncologists (YMO) Group in cooperation with the Thoracic Oncology Working Group of the Arbeitsgemeinschaft Internistische Onkologie (AIO) within the German Cancer Society.
DURATION is an investigator-initiated trial that is supported by the non-profit AIO-Studien-gGmbH (Berlin, Germany) as legal sponsor. Funding and drugs for this trial are provided by AstraZeneca and Celgene.
Ethics approval and consent to participate
Central ethics approval has been confirmed from the Ethics Committee of the Medical Faculty of the University of Heidelberg 24.10.2017 (AFmu-681/2016) and we will not begin recruiting at other centers in the trial until local ethics approval has been obtained.
Written informed consent is obtained from all participants. Additionally, the Paul Ehrlich Institute (competent authority for approval of clinical trials using medicinal products for human use in Germany) approved the study on 03.07.2017.
Consent for publication
Not applicable as no individual patient data are contained in this manuscript.
The DURATION trial received funding from AstraZeneca and Celgene. AstraZeneca and Celgene have not been involved in the study design and has no role in data collection, management, data analysis and interpretation, or in the decision to submit this protocol for publication.
All authors declare that they have no competing conflicts of interest.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Kuon, J., Hommertgen, A., Krisam, J. et al. Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial. Trials 21, 352 (2020). https://doi.org/10.1186/s13063-020-04280-8
- Lung cancer

domain: literature


Colonel Paul Merida is a native of Oakland, California and graduated from the University of California at Davis in 1994. In 1995, he was commissioned and upon completion of TBS and IOC he served from 1996 to 1999 with 3rd Battalion, 8th Marines.
While assigned to 3/8, he served as a Rifle Platoon Commander participating with SPMAGTF-8 in support of Operation Assured Response in the U.S Embassy, Monrovia, Liberia as well Weapons Platoon Commander where he completed a Unit Deployment Program to Okinawa. Upon return from UDP, he deployed again with BLT 3/8 as the 81mm Mortar Platoon Commander and completed a deployment with the 26th MEU. During this deployment he participated in Operation Joint Guardian in Kosovo and Avid Response in Turkey.
From 2000-2002, Colonel Merida transferred to the Marine Corps Combat Development Command where he served as the Staff Secretary and Adjutant within the Warfighting Development Integration Directorate. In June 2002, he left MCCDC and attended Expeditionary Warfare School, Quantico, Virginia where he graduated with honors.
From 2003-2006 Colonel Merida returned to Camp Lejeune where he served with 1st Battalion, 6th Marines. Serving as a Rifle Company Commander, he completed a deployment with the 22d MEU in support of Operation Enduring Freedom in Afghanistan. Upon the battalion’s return from Afghanistan Colonel Merida served as the Battalion Operations Officer for 1/6 in support of Operation Iraqi Freedom.
From 2006-2009 Colonel Merida was assigned to the staff of The Basic School in Quantico, Virginia. During that period, Colonel Merida served as a section head in the instructor group as well as a company commander for two student companies.
In 2009 Colonel Merida attended the Marine Corps Command and Staff College where he was a distinguished graduate and earned a Masters Degree in Military Studies. Following Command and Staff College, he attended the Marine Corps School of Advanced Warfighting and earned a Masters Degree in Operational Studies.
In 2011, Colonel Merida was assigned to 2d Marine Division (FWD) as the G-3 Future Operations Officer in support of Operation Enduring Freedom in Afghanistan. In May, 2012 Colonel Merida took command of 1st Battalion, 6th Marines. In this capacity he participated in a MEU deployment in 2014 with the 22d MEU. In 2015 he gave up command and served as the Regimental Executive Officer for 6th Marine Regiment.
From 2015-2016 he attended the Marine Corps War College, graduating with a Masters Degree in Strategic Studies. In 2016, he was assigned to the Joint Staff, J-5 where he worked strategy, plans, and policy issues on the Iran Desk. In 2018 he was assigned as the Branch Head for the Strategy Branch at HQMC PP&O. From May 2020 to October 2020 he led the 22nd Marine Expeditionary Unit on deployment as Special Purpose Marine Air Ground Task Force, Crisis Response-Africa 20.2.
Currently, he serves as the commanding officer of the 22nd Marine Expeditionary Unit.
His personal awards include Two Bronze Star Medals, one with valor, Defense Meritorious Service Medal, Meritorious Service Medal (two awards), Navy and Marine Corps Commendation Medal (two awards), Combat Action Ribbon (two awards) and various unit commendations and service/campaign awards.


TQFP devices are only 1.2 mm or 1.27 mm thick. Due to their extremely flat design, LQFP devices are suitable for use in notebooks, handhelds and other mobile devices. These devices are available with 44, 48, 64, 80, 100 and 120 pins. The distance between the connectors can be 0.5 mm and 0.8 mm. The size of the TQFP package with 48 pins is 7.0 mm x 7.0 mm. The numbering of the connections is done consecutively from the marking counterclockwise.


A report published by the Centers for Disease Control and Prevention (CDC) in the US has suggested that there was little change in the rate of incidences of foodborne infections in 2007.
The CDC conducted the research as part of its Foodborne Diseases Active Surveillance Network, FoodNet. It said the 10-state report, which examined data from 2007, showed little change in the incidence of some foodborne infections following a period of decline.
According to the research, rates of Campylobacter, Listeria, Salmonella, Shigella, E.coli O157, Vibrio, and Yersinia infection did not decline significantly, while the estimated incidence of Cryptosporidium increased when compared with the three years from 2004 to 2006. Although there have been significant declines in the incidence of some foodborne infections since surveillance began in 1996, these declines all occurred before 2004, the CDC stated.
“The results show that prevention efforts have been partly successful, but there has been little further progress in the most recent years,” said Dr Robert Tauxe, deputy director of CDC’s Division of Foodborne, Bacterial and Mycotic Diseases. “More needs to be done to make our food safer. We are constantly working to help our public health system better detect, investigate and control outbreaks and to understand how to prevent foodborne illnesses from happening in the first place. FoodNet is an important part of our food safety system and is how we measure progress.”
While the FoodNet constituency is similar to the US population, the CDC pointed out that the findings are used to detect trends and should not be generalised for the entire US population.


text:
After learning about Monarchs (which mean King) and chrysalis at school Amelia took to our neighbor's backyard to find, catch, and capture butterflies.
Amelia and Meredith began to notice many of the butterflies they found had damaged wings. They decided it was time to build a Butterfly Hospital to help rehabilitate these insects. I asked Amelia how the healing was going, "Daddy we have almost healed one butterfly. We raise them up on one finger so they learn to get air under their wings again."

domain: biology


text:
Torino vs NapoliSerie A, KO: 17:30 Apr 26, 2021, Stadio Olimpico Grande Torino
Torino host Napoli in an Italian Serie A clash at the Stadio Olimpico Grande Torino with both teams chasing different targets at opposite ends of the table. The Turin club have turned a corner in their quest to beat the drop but face a difficult time against a Napoli team determined to secure Champions League football.
Torino earned a 1-1 draw at Bologna last time out in Serie A. They fought back from a goal down with Rolando Mandragora's second half effort enough to earn them a point.
The Turin club have now gone unbeaten in their last four matches, a run that has taken them out of the relegation zone. They are up to 16th on the table but still dangerously close to the bottom three with 18th place Benevento level on 31 points.
Davide Nicola’ men remain unconvincing at home having claimed just two wins at the Stadio Olimpico Grande Torino all season.
Napoli showed their quality in their previous Serie A fixture, claiming a 5-2 victory over Lazio. Captain Lorenzo Insigne netted a brace while Dries Mertens, Matteo Politano and Victor Osimhen were also on target.
Gennaro Gattuso’s men have been on the rise in recent weeks and put themselves in the mix for Champions League qualification. They are fifth on the table, three points behind fourth place Juventus following a run of seven wins in their last 10 Serie A matches.
While Napoli have looked slightly vulnerable at the back, they have goal threats across the final third. That attacking threat often gives them the edge with a 4-3 victory over Crotone and a 2-0 triumph at Sampdoria among their recent results.
How the bookies view it
Napoli have won three of their last four away matches and should have the edge over Torino.
Head to head
Napoli have a 13-5 advantage from 31 previous matches against Torino. There have been 13 stalemates between both teams, including a 1-1 draw in the reverse fixture back in December.
Players to watch
Striker Andrea Belotti is the top scorer for Torino with 12 goals and is priced at 21/10 by BetVictor to score anytime. Forward Antonio Sanabria has scored five times in his last eight matches and could also be worth a punt in the same market at 11/4 with Unibet.
Napoli have multiple attacking threats but Lorenzo Insigne remains top scorer with 17 goals. Unibet has the forward at 37/20 to score anytime while striker Victor Osimhen is also worth keeping an eye on in the same market at 29/20 with Betfred having found the net three times in his last five appearances .
Anything else catch the eye?
With both teams boasting plenty of quality in attack, the goals market is likely to provide some rewards. Over 3.5 goals is valued at 9/5 by BetVictor while over 2.5 goals is set at odds of 14/19 by SBK.
Napoli have led at the break in two of their last three away matches and could be backed to earn a half time win at 11/8 with SBK. There are likely to be goals in both halves at odds of 7/10 with William Hill.
This Serie A match between Torino and Napoli will be played on Apr 26, 2021 and kick off at 17:30. Check below for our tipsters best Torino vs Napoli prediction. You may also visit our dedicated betting previews section for the most up to date previews.

domain: news


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Something you may not know about me if you come to Critical Hits mainly for the RPG content is that I’m a huge movie nerd. In April of this year I posted a look ahead at the big summer movies of 2010 that I was hoping to see, just as I have done for the last four years running. Iron Man 2 came out in the lead this year and it is actually (unfortunately) the only one from the list that I have seen at the moment.
I wrote in that post that I couldn’t include Tron:Legacy because it isn’t a summer movie and I am very thankful that I can finally see it tonight at midnight! On the other hand Inception didn’t even make my list back in April but between then and its release the trailers convinced me it was a must-see, so I saw a midnight showing and promptly wrote a review of it the next morning.
This year is a bit different from the last few because I am already excited to see a ton of movies in 2011 and we’re not even through December yet! Here’s a look at the movies of early 2011 that I’m most excited to see, and a quick description of why I’m excited about it:
The Green Hornet – January 14th
Staring Seth Rogen, directed by Michael Gondry, and has a direct relation to Bruce Lee. Plus it looks pretty funny. Win! (trailer)
Unknown – February 18th
Liam Neeson in what looks like a role similar to the one he played in Taken. (trailer)
The Adjustment Bureau – March 4th
Matt Damon in a movie based on a Philip K. Dick short story (think Minority Report, Total Recall, and Blade Runner) by the director of the Bourne Ultimatum. (trailer)
Battle: Los Angeles – March 11th
I’m a sucker for alien invasion movies, and this one looks like a better version of Skyline. Also looks along the same lines as Cloverfield or District 9, but possibly with robotic aliens. (trailer)
Paul – March 18th
The next movie from Simon Pegg and Nick Frost. If you need more, they’re playing sci-fi fans who encounter and befriend a real ‘grey man’ style alien voiced by Seth Rogen. (trailer)
Sucker Punch – March 25th
The next movie from Zack Snyder, Sucker Punch looks like it combines the best elements of 300 and Watchmen together into an original story that feels like it’s based on a comic book. Also it combines samurai, robots, machine guns, dragons, and women who kick some serious ass. (trailers)
Your Highness – April 8th
The trailer for this is one of the funniest I’ve ever seen. Danny McBride, James Franco, and Natalie Portman doing a modern style comedy set in a medieval fantasy setting. This is already in the running for potentially the funniest movie of 2011. (trailer)
Thor – May 6th
Really it should be no surprise that this is on the list, but with Kenneth Branagh, Anthony Hopkins, and Natalie Portman involved I’m really hopeful that this one will be a good one. (trailer)
Pirates of the Caribbean: On Stranger Tides – May 20th
Though Orlando Bloom is noticeably lacking from this project so far, the addition of Penelope Cruz and what appears to be a consistent continuation of the best parts of Depp’s performances, this one stands a chance at being one of the best 4th movies ever created (though admittedly that’s not a hard category to outshine so far). (trailer)
X-Men: First class – June 3rd
I’m eager to see how the X-Men franchise reboot will happen, but so far I’m still not thrilled with what I’ve heard about it. However, it’s an X-Men movie so it has a lot of potential ahead of it and we’ll see if director Matthew Vaughn can follow up Kick-Ass adequately.
Super 8 – June 10th
The next movie from J.J. Abrams, and I’ve been waiting for a follow-up to the enticing teaser trailer for months now. I’m hooked at least until I find out some more information about what in the world this movie is going to be!
Green Lantern – June 17th
Again there’s not much justification for comic book movies needed to be on this list, but I will say I disagree with some people and I think the trailer for this makes it look much better than it could have. I’m a fan of Ryan Reynold’s charisma no matter what, and I’m excited to see how this DC franchise looks on the big screen. (trailer)
Cars 2 – June 24th
Pixar has proven that they can do a very good sequel, and the first Cars was a great movie, so I’m interested to see where they go with this one. (teaser trailer)
Transformers: Dark of the Moon – July 1st
Okay, so let’s not think much about the second Transformers and instead look forward to seeing even giant robots fighting with amazing sound effects. I can hope, right? (teaser)
Harry Potter and the Deathly Hallows: Part 2 – July 15th
Considering I read through all of the books specifically to see this after reading the book, I’m excited to see how they series is finished off by Part 2. I was not a fan of the first few movies, but I am really looking forward to this one.
Captain America: The First Avenger – July 22nd
So many comic book movies! Captain America stands out because it takes place in the past and focuses on the origin story of Cap, also because they cast the Human Torch (Chris Evans) but it looks like he’s doing everything he can to live up to the legendary role. My biggest hope is that the Marvel movies of 2011 don’t fall flat and all become simple lead ins for the Avengers movie, but can stand alone on their own merits as well as building towards a unified project. With the director responsible for The Rocketeer doing another period piece about a very much human superhero, I’m already sold.
Cowboys & Aliens – July 29th
Jon Favreau’s next movie starring Daniel Craig, Harrison Ford, Olivia Wilde, and Sam Rockwell taking place in a western setting that features aliens. I guess the straightforward titles tells you that much already. This one is worth keeping an eye on to see what direction the Iron Man director is taking post Iron Man 2. (trailer)
If there’s a movie in early 2011 that you think should be on this list and isn’t , please share! I hope that this list helped point out a few movies you weren’t aware of or hadn’t paid much attention to yet but are interested in seeing now. For the most part I just enjoy having a list all in one place so I can look through and see what movies are coming up that I’d really like to see.
A much further look out and I also spotted an untitled Sherlock Holmes sequel and the next Mission: Impossible movie which would both make the list except that they’re not coming out until December of 2011 or later.

domain: entertainment


text:
Why COVID-19 testing is not recommended for everyone
According to the Centers for Disease Control and Prevention (CDC), testing is not necessary for everyone who experiences symptoms of COVID-19. Wondering whether you or a loved one needs to be tested? Here’s what you should know. If you
Advising patients to routinely take vitamin and mineral supplements is actually not advised.
Top 55 hospitals patients would definitely recommend
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Top 10 apps physicians recommend to their patients
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Ask the St. Elizabeth Expert: What do you recommend for hydration?
CINCINNATI (WKRC) - As the weather warms up and you move your activities outdoors, there is a word of caution to stay well hydrated from sports medicine experts.The team at St. Elizabeth Sports Medicine says that right now, as temperatures outside are warm
Welcome to M3, a confidential test to identify bipolar depression and anxiety symptoms. Your results may be emailed to your health care provider at your discretion.
10 Pediatrician Recommended Toys for Newborns Through Preschoolers (Infographic)
Toys can be very beneficial in assisting with your child's development. Here is a great infographic with 10 Pediatrician Recommended Toys for Newborns Through Preschoolers.
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News articles provided by Beaumont experts showcasing Beaumont Health's achievements in the healthcare community.
Readers’ picks: Top 10 novels recommended by your colleagues
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What is an A1C test and why do we measure it?
Hemoglobin A1C measures blood sugar and is one test used to screen for diabetes and pre-diabetes. When you join the NERD Health and Wellness Center, you will undergo an intake exam with one of our registered nurses and wellness coaches, and you will receive an A1C screening.
10 Disciplines I’d Recommend Everyone Start in Their Twenties
This is one of those posts I hope someone learns something, which can help them in life I hope that for all of my posts – otherwise why am I writing, but, I see this one as a life-giving post for those who will read it and take some of it to heart. My specific target is those who are in their 20’s, who are starting out in their adult life and career. As I’m writing, I’m thinking of my own two sons…
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10 Books that Bill Gates Recommends Everyone Reads
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domain: medical


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MALAYSIA is on a menacing downward spiral fuelled by religious bigotry. We are a growing polarised nation at war with ourselves. The recent years have been marred by reports that show us just how badly divided we are becoming.
Some of us feel as though the damage is already done and our society has reached the peak of desolation where most of us are left feeling despondent about our nation’s future.
Malaysian society has devolved in one way or another; allowing rage, oppression and polarisation to reign supreme and replace societal dogma. Our loyalties and sanities are frequently put to the test. Malaysians are no longer encouraged to have different legitimate opinions and asking the wrong questions could get you in trouble.
The shockingly disgraceful overzealousness portrayed by Islamic authorities and accepted by the majority has made a mockery over something so beautiful, just and peaceful. There are now Muslim-only laundromats, tahfiz schools exempted from safety regulations by default of piety, futsal-playing Muslim men barred from wearing shorts, and the never-ending moral policing of clothes, where we eat, what utensils we use and what animals to blur out during prime time television. All these because Muslims are often reminded that we are easily confused and that there is an ominous threat looming above us that endangers our values.
The recent detention of prominent Turkish writer Mustafa Akyol is a prime example of this: Akyol, whose book “Islam without Extremes: A Muslim Case for Liberty” addresses the concerns and problems present day Muslims face.
Most of his writings centre on Islamophobia, violent extremism, religious bigotry and presents the perfect discourse needed for us to understand how the true teachings of Islam embrace universal humanist values that are often demonised by overzealous preachers of the far, far right.
His detention exposes the hypocrisy our society has succumbed to and just how arbitrary our system has become.
One stark contrast is how local religious authorities treated Indian Islamic preacher Zakir Naik. Despite being banned in India, Bangladesh, Canada and the United Kingdom, Naik was allowed to enter Malaysia and conduct a series of public talks of questionable content.
To the rest of the world, Zakir Naik is known for being a televangelist who spreads Wahhabism; where he justifies revealing Western attire as one of the main causes of rape, supports domestic violence and sexual slavery.
Surely, given his track record, it is clear to see that between the two intellectuals, who actually poses a greater threat to Malaysian democracy and our constitution.
Islam is one of the world’s great religions but because of the pre-existing vacuum of knowledge and differing interpretations of Holy Scriptures, our society is at risk of increasing fundamentalism. Those in key authoritative positions may have little knowledge and intellect, whilst those who put them there may do so for political mileage.
A dangerous game that takes advantage of our insecurities triggered by globalisation and deep-rooted in hypocrisy. A dumb nation is easier to control but bear in mind, ignorance can breed fear, which too easily can turn to hatred and this can mark the absolute destruction of democracy, where there will be no victors from either sides.
And this is where we are right now: Malaysians are held hostage by repulsive religious bigotry sanctioned by the very same political elites who are free to carry on with their hedonistic way of life.
As we lament over the sad state of religious liberty and think of ways to rise above the ashes of hate, it’s worth remembering Akyol’s parting words in a statement he issued shortly after his release.
“The practice of Islam must be on the basis of freedom, not coercion, and governments shouldn’t police religion or morality.”
Malaysians must be able to define, differentiate and separate between extreme theology and ideology in Islam and muster the courage to challenge this. It is essential for us to denounce the brand of Islam that idolises violence and intolerance.
Fighting hate-filled doctrines must be done through civil discourse and sensible actions because only the overzealous self-righteous cry out judgments against others as a way to conceal the skeletons kept hidden in their own closets.
There is a dire need to fortify our democratic and diverse society; and to restore all hope, respect and civility; remaining silent in the ugly face of religious intolerance, insecurity and hypocrisy is not an option.


External Size (LxWxH):2130*1060*475-785mm±10mm
Mattress Platform :L1925*W900±10mm
Safe Working Load:250kg
Voltage and frequency:100-240V – 50-60HZ
Plug as required(hospital grade)
Linear motor:3 pcs
5″ double side cators, central locking system:4 pcs
ABS oasis side rail extra height:1 set
ABS oasis bed ends with safe lock:1 set
Stamping forming bed platform:1 pc
Plastic socket inside PP guardrail for phone or glasses:2 pcs
Φ70mm wall bumper wheel:4 pcs
IV Pole:1 set
IV Pole prevision:4 pcs
Drainage hook:2 pcs
Central locking pedal:2 pcs
Hand controller:1 pc
We provide a standard 1 year warranty, optional to be increased.
1% free parts of the total quantity will be provided together with goods.
The product that is damaged or fails due to the manufacturing problem within one year after the purchasing date will gain free spare parts and assembling drawings from the company.
Beyond the maintenance period, we will charge the accessories, but the technical service is still free.