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Inducing senescence sensitizes pancreatic tumours to therapies




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Nuclear receptor crosstalk — defining the mechanisms for therapeutic innovation




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Combining radiolabelled therapies for neuroendocrine neoplasms




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Age influences structural brain restoration during weight gain therapy in anorexia nervosa




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Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis




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High-risk additional chromosomal abnormalities at low blast counts herald death by CML




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Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial




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Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke




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Parkinson disease and the immune system — associations, mechanisms and therapeutics




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Correction: Humanized bone facilitates prostate cancer metastasis and recapitulates therapeutic effects of Zoledronic acid in vivo




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Anti-obesity therapy with peripheral CB1 blockers: from promise to safe(?) practice




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Innovations in dialysis membranes for improved kidney replacement therapy




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Breakthrough therapy designation: A primer


Breakthrough therapy designation (BTD) is the newest of four expedited programs developed by the U.S Food and Drug Administration (FDA) to accelerate the development and review of novel therapies that target serious conditions. The public response to the program has been largely positive, and dozens of drugs have successfully received the designation. However, the FDA denies many more requests than it grants. In fact, as of March 2015, less than one in three of the BTD requests submitted have been granted. By contrast, roughly 75 percent of the requests for fast track designation (another of the Agency’s expedited programs) were granted between 1998 and 2007. This discrepancy suggests ongoing uncertainty over what exactly constitutes a “breakthrough” according to the FDA’s criteria.

On April 24, the Center for Health Policy at Brookings will host an event, Breakthrough Therapy Designation: Exploring the Qualifying Criteria, that will discuss qualifying criteria for the BTD program using real and hypothetical case studies to explore how FDA weighs the evidence submitted. Below is a primer that describes the definition, value, and impact of BTD.

What is BTD?

BTD was established in 2012 under the Food and Drug Administration Safety and Innovation Act, and is intended to expedite the development and review of drugs that show signs of extraordinary benefit at early stages of the clinical development process. However, BTD is not an automatic approval. The drug still has to undergo clinical testing and review by the FDA. Rather, BTD is designed to facilitate and shorten the clinical development process, which can otherwise take many years to complete.

What criteria does FDA use to evaluate potential breakthroughs?

In order to qualify for the designation, a therapy must be intended to treat a serious or life-threatening illness, and there must be preliminary clinical evidence that it represents a substantial improvement over existing therapies on at least one clinically significant outcome (such as death or permanent impairment).

In considering a request for BTD, FDA relies on three primary considerations:

1) the quantity and quality of the clinical evidence being submitted;

2) the available therapies that the drug is being compared to; and

3) the magnitude of treatment effect shown on the outcome being studied.


In practice, however, it can be difficult to define a single threshold that a therapy must meet. The decision depends on the specific context for that drug.  In some cases, for example, the targeted disease has few or no treatments available, while in others there may be several effective alternative treatments to which the new therapy can be compared. The request may also be made at different stages of the clinical development process, which means that the amount and type of data available to FDA can vary. In some cases, early evidence of benefit may disappear when the drug is tested in larger populations, which is why FDA reserves the right to rescinded the designation if subsequent data shows that the therapy no longer meets the criteria.

How many therapies have received the designation?

As of March 2015, FDA had received a total of 293 requests for BTD. Of these, 82 received the designation, and 23 have since been approved for marketing. Ten of these approvals were new indications for already approved drugs, rather than novel therapies that had never before received FDA approval.

What are the benefits of BTD?

For drug manufacturers, it is about the intensity and frequency of their interactions with FDA. Once the designation is granted, the FDA takes an “all hands-on-deck” approach to providing the manufacturer with ongoing guidance and feedback throughout the clinical development process. Products that receive BTD are also able to submit portions of their marketing application on a rolling basis (rather than all at once at the end of clinical trials) and BTD can also be used in combination with other expedited programs in order to further reduce the product’s time to market.

For patients, the potential benefits are straightforward: earlier access to therapies that may significantly improve or extend their lives.

How does BTD relate to the other three expedited programs?

The other three expedited review and development programs—fast track designation, priority review, and accelerated approval—are also geared at facilitating the development and approval of drugs for serious conditions. These other programs have been in place for over 15 years, and have played a significant role in accelerating patient access to new therapeutics (Table 1). In 2014 alone, 66 percent of the 41 drugs approved by FDA's Center for Drug Evaluation and Research used at least one of these four pathways, and 46 percent received at least two of the designations in combination.

Table 1: Overview of FDA’s Expedited Review Programs


 Adapted from FDA's Guidance for Industry: Expedited Programs for Serious Conditions - Drugs and Biologics

Authors

      




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Breakthrough therapy designation: Exploring the qualifying criteria


Event Information

April 24, 2015
8:45 AM - 4:45 PM EDT

Ballroom
The Park Hyatt Hotel
24th and M Streets, NW
Washington, DC

Register for the Event

Established by the Food and Drug Administration Safety and Innovation Act of 2012, breakthrough therapy designation (BTD) is one of several programs developed by the U.S. Food and Drug Administration (FDA) to speed up the development and review of drugs and biologics that address unmet medical needs. In order to qualify for this designation, the treatment must address a serious or life-threatening illness. In addition, the manufacturer (i.e., sponsor) must provide early clinical evidence that the treatment is a substantial improvement over currently available therapies. The FDA is working to further clarify how it applies the qualifying criteria to breakthrough designation applications.

On April 24, under a cooperative agreement with FDA, the Center for Health Policy convened a public meeting to discuss the qualifying criteria for this special designation. Using examples from oncology, neurology, psychiatry, and hematology, the workshop highlighted considerations for the BTD application process, the evaluation process, and factors for acceptance or rejection. The discussion also focused on key strategies for ensuring that the qualifying criteria are understood across a broad range of stakeholder groups.


Video

Event Materials

      




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Event recap: Lessons learned from two years of breakthrough therapy designation


The breakthrough therapy designation (BTD) program was initiated by the U.S. Food and Drug Administration (FDA) in 2012 to expedite the development of treatments for serious or life-threatening illness that demonstrate “substantial improvement” over existing therapies. The program has since become a widely supported mechanism for accelerating patient access to new drugs. As of March 2015, FDA has received a total of 293 requests for BTD. However, it has granted just  82 (28%), which indicates an ongoing lack of clarity over what exactly meets the criteria for the designation.

On April 24, the Center for Health Policy at Brookings convened a public meeting to explore the designation’s qualifying criteria and how FDA applies those criteria across therapeutic areas. Panelists used real-world and hypothetical case studies to frame the discussion, and highlighted major considerations for the application process, the FDA’s evaluation of the evidence, and the key factors for acceptance or rejection. The discussion also identified strategies to ensure that qualifying criteria are well understood. Here are the five big takeaways:

1.  The BTD program is viewed positively by drug companies, researchers, advocates, and others 

Across the board, participants expressed enthusiasm for the BTD program. Industry representatives noted that their experience had been extremely positive, and that the increased cooperation with and guidance from FDA were very helpful in streamlining their development programs. Receiving the designation can also raise a drug company’s profile, which can facilitate additional investment as well as clinical trial patient recruitment; this is particularly important for smaller companies with limited resources.

Patient and disease advocates were likewise supportive, and expressed hope that the early lessons learned from successful breakthrough therapy approvals (which have been mostly concentrated in the oncology and antiviral fields) could be translated to other disease areas with less success. However, while BTD is an important tool in expediting the development of new drugs, it is just one piece of broader scientific and regulatory policy landscape. Accelerating the pace of discovery and development of truly innovative new drugs will depend on a range of other factors, such as developing and validating new biomarkers that can be used to measure treatment effects at an earlier stage, as well as establishing networks that can streamline the clinical trial process. It will also be important to develop effective new approaches to collecting, analyzing, and communicating information about these treatments once they are on the market, as this information can potentially be used by FDA, providers, and patients to  further improve prescription drug policy and medical decision-making.

2.  BTD requests far outnumber those that actually meet the qualifying criteria

Since the program began, less than 30 percent of requests have received BTD designation. A substantial majority were denied at least in part due to either a lack of data or problems with the quality of the data, or some combination of the two. For example, some sponsors requested the designation before they had any clinical data, or submitted the request using clinical data that was incomplete or based on flawed study designs. Many requests also failed to meet the Agency’s bar for “substantial improvement” over existing therapies.

One reason for the high denial rate may be a lack of a clear regulatory or statutory bar that could be used as a definitive guide for sponsors to know what is needed to qualify for the designation. BTD denials are also confidential, which means that sponsors effectively have nothing to lose by submitting a request. Going forward, manufacturers may need to exercise more discretion in deciding to request the designation, as the process can be resource- and time-intensive for both sides.

3.  There is no single threshold for determining what defines a breakthrough therapy

About 53 percent of the 109 total BTD denials were due at least in part to the fact that the drug did not represent a substantial improvement over existing therapies. During the day’s discussion, FDA and sponsors both noted that this is likely because the criteria for BTD are inherently subjective. In practice, this means there is no clear threshold for determining when a new therapy represents a “substantial improvement” over existing therapies. Designation decisions are complex and highly dependent on the context, including the disease or condition being targeted, the availability of other treatments, the patient population, the outcomes being studied, and the overall reliability of the data submitted. Given the multiple factors at play, it can be difficult in some cases to determine when a new product is potentially “transformational” as opposed to “better,” especially for conditions that are poorly understood or have few or no existing treatments. In making its determinations, FDA considers the totality of the evidence submitted, rather than focusing on specific evidentiary requirements.

4.  Early communication with FDA is strongly recommended for BTD applicants

Roughly 72 percent of the BTD denials related at least in part to trial design or analysis problems, which led several people to suggest that sponsors engage with FDA prior to submitting their request. Though there are several formal mechanisms for interacting with the agency, informal consultations with the relevant review division could help sponsors to get a better  and much earlier sense of what kind of data FDA might need. This early communication could both strengthen viable BTD requests and reduce the number of frivolous requests.

5.  FDA may need more resources for implementing the BTD program

Drugs that receive breakthrough designation are subject to much more intensive FDA guidance and review. However, when the program was established in 2012, Congress did not allocate funding to cover its costs. There have been ongoing concerns that the program is exacting a significant toll on FDA’s already limited resources, and potentially affecting the timeline for other drug application reviews. These concerns were reiterated during the day’s discussion, and some suggested that Congress consider attaching a user fee to the BTD program when the Prescription Drug User Fee Act comes up for reauthorization in 2017.

Authors

      




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Say it with Butterflies - Green Start-Up Grows Monarch Butterflies for Events, Therapy & Conservation

Here is an interesting buisness idea; grow butterflies to let fly at special ocasions and at the same time help the enviornment as well as people with special needs. The project is called Mariposeando (Spanish for something




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How do dogs feel about being therapy animals?

Anyone who knows dogs probably knows the answer to this question.






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St. Jude Children's Research Hospital® opens first proton therapy center for children - Proton Therapy at St. Jude

Proton therapy will be used to treat brain tumors, Hodgkin lymphoma and other solid tumors and is the most advanced form of radiation technology available to patients.




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Sorrento Therapeutics and Mount Sinai join forces to develop Covid-19 antibody shield

Sorrento Therapeutics and Mount Sinai Health System in New York City have joined forces to develop an antibody cocktail they hope will shield against Covid-19 infection for up to two months.





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Can virtual therapy help us cope with the coronavirus lockdown?

Many people are turning to virtual therapy and mental health apps to cope with the stress of the coronavirus pandemic, but they may not be as helpful as talking face to face




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Concert to cheer up children undergoing chemotherapy at Parel hospital

So many of us have lost someone we know to cancer. So when 15-year-old Devika Madgavkar, who was volunteering at the Tata Memorial Centre and working with kids with cancer, asked Alfred D'Souza, the director of her choir Stop-Gaps Junior Choral Ensemble, if they could do something to cheer up the children undergoing chemotherapy, he thought, "why not?"

And Carnival in Song was born. "Madgavakar wanted to do something for the kids, who she observed were quite self-conscious and distant after they lost their hair. Also, many of them hail from a low social economic background. The event is just before Lent, which begins on March 6, and as it's the season of hope, we wanted to brighten up their li­ves. I prepared two choirs and reached out to others, who agreed immediately," says D'Souza.


The Salvation Singers

The audience will get to hear ha­ppy numbers, and renditions of peppy tracks with a samba or calypso beat, akin to what you hear at a carnival, shares D'Souza, adding that while the Stop-Gaps Choral Ensemble will be performing Brazil and Senorita, The Salvation Singers will offer a medley of Hindi songs, and Siddharth Meghani will perform some Elvis Presley tracks. The line-up will also include The Victory Chorus Line, and soloists such as Ella Atai, Kim Cardoz, Mehmood Curmally and Darren Das, accompanied by Mimosa Almeida Pinto (piano) and Ishan Jadwani (drums), besides dancers on stage.

"We've been planning this since October. We have a lot of kids aged between five and 15 years, who have their term exams at the moment, but yet th­ey have been practising," adds D'Souza. All proceeds from the evening will be given to the centre's Runners of Hope Initiative.

ON March 1, 7.45 pm onwards
AT St 
Andrew's Auditorium, St Andrew's College, St Dominic Road, Bandra West 
LOG ON TO bookmyshow.com

CALL 26410926
COST Rs 300 onwards

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Vino therapy in Bandra

Two decades ago, drinking wine was restricted to snooty pseudo-intellectuals who turned the experience into flavour profiles of tannins and acids, melons and mango, and grape varieties that we could barely pronounce.

We now sip in times when the pourer, who once intimidated us with technical terms, explains the story of the vineyard, the grape and body with passion in layman’s terms.

When we stepped into 266 Wine and Bar Room, we were quickly reminded of the Kala Ghoda Wine Bar that recently opened in the much-loved backroom of Kala Ghoda Café. The space is done up in hues of light blue and grey, with light fixtures adding a warm, amber glow from low-wattage tungsten bulbs. We settle into blue sofas, preferring the comfort to the high stools that may turn tricky after a few glasses.


266 Charcuterie and Cheese Board

The 266 Charcuterie and Cheese Board (Rs 675) is an indulgence with brie, camembert, cheddar, strawberries, walnuts, olives and chicken and pork cold cuts. Between nibbles and sips, we realise this is a space we’d love to hang out at for conversations or even some alone time.

The platter beautifully compliments the wines. The thirstier one among us has signed up for an old world red wine flight (Rs 1,800) that takes her from an Italian pinot noir by Folonari, which is crisp and medium-bodied, to a full-bodied French syrah by Domaine Gayda, a Spanish Monastrell and finally, a fresh Italian Umani Ronchi of Montepulciano d’Abruzzo. Of the lot, the syrah’s peppery, fruity notes get the highest applause.

World maps should have been taught according to wine regions of the world, we think, as we enjoy the joyride through this mini trip across some of the world’s finest wine counties. On the other hand, we sip a honeyed South African Chenin blanc by Tall Horse (Rs 850) which is tart-y, fruity and light on the palate.


Tomato stew with prawns and Malabari paratha

The food at this wine bar draws our attention too. We take a risk and order the tomato stew with prawns (Rs 575) that comes with a side of flaky, buttery Malabari paratha (Rs 60). It’s a great example of wine pairing with Indian food. The broth is sweet, tangy and cuts the acidity of the wine. With the cheese board now reduced to crumbs of brie and cheddar, we settle for a dark chocolate and olive oil mousse (Rs 425) that gives our spirited sojourn a bittersweet (pun not intended) end.

AT 266 Wine and Bar Room, next to Shopper’s Stop, Linking Road, Bandra West
TIME 4 pm to 12 am

CALL 8879101350

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266 Wine and Bar Room didn't know we were there. The Guide reviews anonymously and pays for meals





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Coronavirus outbreak: Doctors put their faith in BCG vaccine therapy

Apart from plasma therapy, COVID-19 patients who are in critical condition, will soon have another kind of treatment, to help fight the infection. Mumbai-based Haffkine Institute, which last month had submitted a proposal to conduct a clinical trial to use the anti-tuberculosis Bacillus Calmette-Guérin (BCG) vaccine, as a therapeutic treatment received a nod for it from the Drug Controller General of India on Friday.

Around 30 COVID-19 patients, who have moderate or severe symptoms, will be part of the trial run, starting next week. "The BCG vaccine strengthens immunity and research has shown that it can be used as a therapeutic treatment, to help patients fight the infection. We received an approval from the DGCI and are waiting for the clinical registration number from the ICMR, which should come in a couple of days," said a senior official from the Medical Education and Drugs (MED) department.

While the trial will be carried out by the Haffkine Institute and led by Dr Usha Padmanabhan, it is being monitored by the MED department.

Mumbai has the highest number of Coronavirus-related deaths in the state, as well as in India. The official added that once the trials are successful, patients who are critical, especially in cities like Mumbai and Pune, will be able to benefit from it. "Unlike new drugs, the BCG vaccine is already in production and will be easily available. So far, the institute has carried out preliminary studies and they have come across positive results," the official said.

Dr Rajesh Deshmukh, managing director of the Haffkine Institute in Parel, said that they are likely to start the trial next week. "It will take place at the BJ Medical College in Pune. We have carried out the preparations and the scientists are almost ready," he said.

Based on the preliminary findings of the research for the trial, the effect of the virus can be reduced among patients, if they are given a dose of the BCG vaccine. The official said that the vaccine will help reduce the severity of the symptoms among patients.

Catch up on all the latest Mumbai news, crime news, current affairs, and a complete guide from food to things to do and events across Mumbai. Also download the new mid-day Android and iOS apps to get latest updates.

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Plasma therapy: To use or not to use...

While trials on plasma therapy for COVID-19 continue, they have sparked debate among medical professionals. While one set of experts feels that plasma therapy can work wonders with a supportive line of treatment, the other set opines that it is too premature to make such claims without thorough clinical evidence.

Interestingly, the first set of experts is now further puzzled as to whom they should administer plasma therapy. That's because of the high risk involved as COVID-19 patients may still have existing ailments that may not respond well to plasma therapy.

The concern was raised after the recent death of a 52-year-old man who was given plasma therapy at a Mumbai hospital. The man had co-morbidities and was on ventilator support.


Dr Anoop Kumar, consultant and chief of Critical Care Medicine at BM Hospital, Calicut

Premature to consider it
Dr Asha Kishore, medical director, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, said, "While there have been a few reports of convalescent plasma therapy being effective in treating COVID patients, unless there is a clinical study it is premature to consider it as an accepted form of treatment. It should be considered experimental therapy and should be monitored and regulated by the health ministry. Even data from China is too limited to confirm successful experiment of plasma therapy."

"Our transfusion medicine department has applied for participation in a clinical trial of convalescent plasma for the treatment for COVID-19 called by the Indian Council of Medical Research (ICMR). The ICMR's sponsored trial will be conducted to evaluate the safety and efficacy of convalescent plasma in patients with moderate COVID-19 infection. We are awaiting approval," said Dr Asha.

Against immunology principle
Dr Wiqar Shaikh, senior allergy and asthma specialist, who had treated the 52-year-old Byculla resident who was treated at home and recovered from COVID-19, said, "Plasma therapy means giving antibodies from a COVID cured patient to one still suffering from it. This is not within the principle of immunology. When a person has a viral infection, the first reaction of the body's immune system is to form IgM (Immuno Globulin M) antibodies and IgG (Immuno Globulin G). However, these are not the important defences against a virus. When the virus enters a body, it does so by mistake and cannot survive within the body and hence enters a cell to survive." Dr Shaikh added, "The COVID virus is an RNA virus, which cannot replicate on its own, it requires the cell apparatus to multiply. Whenever the immune system identifies a virus containing cell, two types of cells are activated. Both are T-lymphocytes, the first category is the cytotoxic T-lymphocyte and the second is the Natural Killer (NK) T-lymphocyte, both of which destroy the virus containing cell using bodily chemicals called 'perforins' and 'granzymes'. This cytotoxic and NK cells develop a memory for the virus within the body, and when the person gets infected with the same virus again, the memory cytotoxic and NK cells launch an immediate attack and kill the virus. Therefore, antibodies (plasma therapy), has a very poor role in defence against COVID and hence is of no use, claims Dr Shaikh.


Dr Asha Kishore, medical director, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram

"There are no double-blind placebo-controlled trials anywhere in the world of plasma therapy actually helping in recovery of serious COVID patients. Moreover, such clinical research is a welcome move, but it takes months or years of painstaking research," said Dr Shaikh.

In favour of plasma therapy
Dr Anoop Kumar, consultant and chief of Critical Care Medicine at BM Hospital, Calicut, said, "The Kerala government was concerned about the rapid rise in COVID-19 cases and called for a meeting of well-known health professionals in Kerala on March 20. At the meeting it was agreed to make use of plasma therapy, as we have come across case studies of successful results in China, South Korea, and other countries. However, it is yet to be published in the international journal."

"Plasma therapy has been effective in various virus outbreaks in the past, such as Nipah virus in 2018, H1N1 in 2008 and even the 1918 flu outbreak," said Dr Anoop, adding, "We intend to collect plasma from patients who have recovered from COVID-19. For instance, a 55-year-old recovered patient can donate around 800ml of plasma from the blood, and this can save four lives with a mere 200 ml of plasma."

However, donor protocol mandates that the donor should not have any fever, or foreign travel history or respiratory infection, and should have remained in self-isolation for 14 days post discharge and the swab collected after self-quarantine period should be negative.

200
Quantity in ml of plasma required for treatment

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COVID-19 Outbreak: No evidence that plasma therapy can be used for treatment, says Health Ministry

New Delhi: The Health Ministry on Tuesday said currently plasma therapy is at the experimental stage and there is no evidence yet to support that it can be used as a treatment for COVID-19.
Addressing a press briefing, Health Ministry Joint Secretary Lav Agarwal said currently there are no approved therapies for COVID-19 and there is not enough evidence to claim that plasma therapy can be used for the treatment of the disease.

"ICMR has launched a national-level study to study the efficacy of plasma therapy in the treatment of COVID 19," he said.

"Till ICMR concludes its study and a robust scientific proof is available, plasma therapy should be used only for research or trial purpose. If plasma therapy is not used in a proper manner under proper guidelines, then it can also cause life-threatening complications," said Agarwal.

The official said that the doubling rate of coronavirus cases now stands at 10.2 days.
He further said that in the last 24 hours, 1,543 new cases of COVID-19 have been reported, taking the total cases to 29,435.

"6,868 COVID-19 patients, which is 23.3 per cent of total cases, have recovered so far," he added.

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Dosage mapping tracks cancer radiotherapy more closely

A non-invasive system being developed by EU-funded researchers could make radiotherapy a safer and more-effective treatment for cancer patients by creating a visual dosage map of the tumour and the surrounding healthy tissue.




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All aboard! Taking a toy train ride from Neral to Matheran


View from the train before entering One-Kiss Tunnel

The tiny hill station of Matheran is a far cry from the peace and serenity that its British founder Hugh Poyntz Malet yearned for. In the 1850s, Indian Civil Service Officer Malet was the Thane collector and while camping below in the village of Chowk, he climbed up the hill-top to explore the region finding it lush green with clean air and water springs, an ideal spot for a vacation. In love with the place, he frequented it with friends and family. Soon, the then Governor of Bombay, Lord Elphinstone, visited the place to make it as a site for his bungalow (still known as Elphinstone Lodge). The rest is history.

Today, over 160 years later, Matheran has lost much of its peace to commercialisation, but it retains some of its charm and character. It remains an eco-sensitive zone with no motorised vehicles, allowing only for horse rides, carts and cycle rickshaws. Though paver blocks have surfaced much of the red soil is intact, and it remains a quick getaway from fast-paced Mumbai.


Peerbhoy original loco

Track record
The journey is fun if you are in a group as it takes just about two hours for the entire ride. Reach Neral on the Mumbai-Pune line and the Matheran narrow gauge train station is adjacent to it. The station and the line are well maintained and are in the tentative UNESCO World Heritage List. Tickets are available on the spot with no prior or on-line bookings due to its limited capacity. The Central Railway runs about 102 services every week (see box). With a width of two feet, it is one of India’s narrowest running passenger railways, and is similar to the Darjeeling Hill Railway.


Matheran Railway station

After booking our tickets, we settle down in our seats. We note that ticket checkers are quite strict. As the mini train pulls out, the initial stretch runs parallel to the Karjat railway line and we spot the local trains pass by, but a sharp right and a steep climb runs the train between two hillocks and the spirals begin. The railway line that was built as a private venture of the Peerbhoy family between 1901 and 1907 still maintains most of its original layout, except for a few stretches. The line winds around the mountain in spirals taking us 2,625 feet above sea level!


Token Machine

High on geography
The train chugs along slowly, at only 13 kmph. The first station is after a distance of 4.8km called Jummapatti. Here, the road that had vanished meets the rail again and we spot motor vehicles speeding by. The line operates on the old token signalling system and the train comes for a brief halt here. Steam trains ran on the stretch till the early 1980s; these were replaced with diesel locomotives in 1984. As the train proceeds, there are three stretches, where we spot our train as it zigzags the curves to avoid reversing points.

The next station is Water Pipe Road, called so due to its proximity to the twin metal water pipes that make their way to the station. It’s another place where tokens are exchanged. During the journey, the rail intersects the road at several places. A little ahead, we enter the One-Kiss Tunnel, popularly named so because it gives a couple time for just a kiss! The entire line has over 121 bridges (mostly minor), 221 curves and only one tunnel. As the train reaches the next station Aman Lodge, we spot tourists walking along the train and more crowds.


Picnickers at Echo Point/PICS/RAJENDRA B. AKLEKAR

This is the closest station to Dasturi Point till where motor vehicles are allowed. The railways have a number of special trains to cater to this crowd as beyond this point besides the train, only horse carriages, cycle rickshaws and carts are allowed. After we cross Aman Lodge, we reach Matheran in 20 minutes, and as we alight, the locomotive goes ahead in a spiral loop to make way for the return journey.

WHAT TO SEE
Located in the Sahyadris at 2,625 feet above sea level, Matheran has 38 points, including a lake. Panorama Point provides a 360-degree view of the surroundings and Neral, Charlotte Lake and Celia Point offer nice views of the dam. Echo Point, is a must-visit too.

While in Matheran
The marketplace on the main street is ideal for knick-knacks, curios and food items like chikki and fudge.
Phone network works well in the market, but weaken elsewhere.
Villagers are co-operative but remember that Matheran has inadequate medical facilities.


Ali Akbar Adamjee Peerbhoy

Remembering a legacy
“The story of the Matheran railway is intriguing. By the turn of the century, the hill resort became popular during summer vacation. Once, after arriving from Mumbai to Neral, Sir Adamji was unable to reach Matheran as no horses were available throughout the day due to the heavy rush. He returned with the thought that of improving things and came up with an idea of a small railway to connect uphill. It was the fastest available mode of transport and he was ready to fund it. This historic decision changed the destiny of the hill station. The next time he visited Matheran was only after his own railway was built,” recalls Ali Akbar Adamjee Peerbhoy (inset), second great-grandson of Sir Adamjee Peerbhoy. His forefather built the line as a family enterprise over a century ago.

Toy train schedule
Monday: 17 services Tuesday to Thursday: 14 services Fridays: 21 services Weekends: 22 services
COST 1st class (adult): R300, 2nd 2nd class (adult):Rs 75. NOTE: Bookings are done only at Neral station

Travel by road
If you prefer to drive down by the road, set your phone map to Dasturi Naka, the entry point into Matheran. It’s until here that motorised vehicles are allowed. It has ample parking space. From Dasturi Point, you can either walk up to Matheran — it’s a 20-minute trail — or opt for cycle rickshaws, horse rides or the train. The Aman Lodge station is next to the Dasturi Point car park. The services between Aman Lodge and Matheran is frequent and is a 10-minute-long-journey.

Rs 55k
The cash you will have to shell out if you wish to book an entire train with its steam engine!

Also read: Matheran toy train finally begins to run on the entire 21-km stretch to Neral from January 26

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Psychotherapist Nupur Dhingra Paiva on how parents' love is essential for kids


Nupur Dhingra Paiva with daughters Tara, 9, and Isabelle, 6. Pic/Shadab Khan

When five-year-old Armaan walked into child psychotherapist Nupur Dhingra Paiva's clinic, her impression about the kid, whose shoulders were hunched over, was that he was "weighed down by something significant". Armaan's mother would later tell her how he felt unloved, wanted to run away from home and even shoot himself. But, it wasn't until Armaan's father joined the therapist and his wife for chat, an hour later, that Paiva noticed something alter in the child. The kid slowly crawled into his father's lap, and curled up there like a little prawn, Paiva recounted. That the child was craving for his dad's attention was a given.

Vignettes like these form the crux of Paiva's new book, Love and Rage: The Inner Worlds of Children (Yoda Press), where she breaks down conversations she has had in her healing room with both parents and children, to reiterate how love and affection is central to influencing a child's personality. "I felt an urgent need to communicate with the world that what comes into our consulting room is not crazy or bizarre -it is the stuff of ordinary life - ordinary conflicts, struggles and joys. And that mental health distress in adolescence and adulthood is almost entirely based on early life experience, from conception onwards," says the Delhi-based clinical psychologist, of why she wrote the book. "Adults who are interacting with children, as parents, teachers or carers, are sometimes far removed from the lived experience of the child. They become task focussed and outcome oriented - it becomes a lot about achievement, growth and the end result of happiness," she adds. In doing so, Paiva says that people forget "that the growth of the personality is a complex, slow process that needs nurturing".

Here, Paiva, who is also mother to two daughters, offers an "only love-not rage" guide.

>> It takes two
When a child is angry with one parent, it helps to have an available alternative. I have to add that I am not necessarily talking about the heteronormative two parents - male-female couple. Children need a diversity of responsible caregivers, someone who will take it upon themselves to keep the child's emotional needs in mind. The role of mother and father is about a mental attitude, the function they play for the child. It does not have to be a biological parent.

>> We need daddy
Often women find it difficult to let men get involved in caregiving tasks like feeding, bathing and putting to sleep. When a child has emotional access to their fathers, the diversity of experience offers them a wider range of seeing how to live in the world, because men and women live in the world quite differently. Just as an involved father gives a son a sense of someone to look up to, he gives a daughter an experience of being loved and valued - something she will carry with herself into future relationships with men.

>> Prep for school
The first couple of years of kindergarten are not about learning shapes or the alphabet, it is about learning to separate from home. It is a physical/emotional wrench, leaving safety and going to another space - one that can be fun and engaging, provided we can get over the fear of separating from the people we feel safe around. Once children are helped to adapt to this huge change, they can get on with learning. Otherwise, anxiety hampers learning for years afterwards.

Start early with picture story-books or perhaps even a visit to the school for the child to see what it looks like a month or so before the emotional temperature rises in April. Be prepared for repetition for as every parent of a young child knows, once is never enough. Stories that matter the most must be repeated endlessly, without variation so that they can sink in. The story of how everyone leaves home and goes to school is of central emotional import. In fact, it is a rite of passage.

>> Play hard
Using our bodies is a release for everything - anger, anxiety and other feelings - that get stuck in our muscles. In the emphasis on growing children's minds [or getting them to finish homework and projects], we forget about how important it is to be using their bodies. Children are calmer and more attentive, when they have had an experience of using their muscles in activity, especially free play.

>> It's okay to cry
Never tell a child not to cry. All children cry, for all sorts of things, so it is important to first figure out what the crying is trying to communicate. Simply telling a child to stop crying without first trying to understand what is under it, will damage their relationship with you. If the crying is because of sadness, then telling them to stop crying is plain selfish. We do it because we can't bear their expression of sadness. It is far healthier to accept that they are sad, and give them a hug. This kind of acceptance lets them know that while nothing can be done about it, at least their experience is being validated and acknowledged.

>> Don't ignore
Ignoring feelings teaches your child that you don't particularly care for his feelings, just his actions or his/her compliance. This only ensures that the feelings will reappear in a form that is harder to link to its source. In other words, the child will use a defence in order to deal with a feeling, and the anxiety its presence creates.

>> Keep it real
I am not advising that people deny that they also can get angry with their children. "Only love" is not a reality. My aim is to be real with my relationships, including my children. So, I freely express affection - lots of hugs and physical warmth, an hour at bedtime talking about their day and their worries. I also freely express disapproval or annoyance. I explain, and negotiate. As a result, I have very opinionated children who are expressive and open, including about their anger with me or their father. We accept it as real and engage with it as much as is possible at the time.

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