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Cell therapy for eradicating cancer

cell therapyEngineered CAR T-Cell Therapy

The immune system has evolved to protect the body from invading pathogens or external harmful materials by identifying these foreign bodies through “non-self” antigens, which are molecular signatures that they carry and are foreign to the body. A central function of the immune system is to discriminate between “self,” which is recognized through antigens normally present in the body and borne by cells, proteins, sugars or lipids, and “non-self”, which is detected through abnormal or foreign antigens. Cancer cells thrive, in part, because they trick the immune system into treating them as self, even though they express abnormal antigens, and thus immune tolerance occurs when the immune system fails to recognize and attack tumors. Breaking immune tolerance is an important aspect of most immuno-oncology based therapeutics because it enables the immune system to recognize and treat tumors as nonself and lead to tumor destruction.

Cellectis’ therapeutics programs are focused on developing products using our gene editing platform to develop genetically modified T-cells that express a Chimeric Antigen Receptors (CAR) and are designed to target and kill cancer cells. CARs are artificial molecules that, when present at the surface of immune effector cells, will enable them to recognize a desired protein, or antigen, and trigger the killing of cells harboring this antigen at their surface (target cells). Immune cells -most usually T lymphocytes- can be engineered to express a CAR able to recognize proteins present at the surface of cancer cells. Upon cell-to-cell contact between effector and targeted cells, antigen recognition will activate the effectors, giving them the signal to attack their targets, and leading ultimately to the killing of cancer cells.

Leukemia

Leukemia is a cancer that originates in the blood stem cells (immature blood cells) which are found in the bone marrow. The blood stem cells can become either lymphoid stem cells or myeloid stem cells. Lymphoid stem cells turn into lymphocytes, a type of white blood cell. Lymphocytes are usually found in the blood and various parts of the lymphatic system, particularly in the lymphatic ganglia and the spleen. Lymphocytes manufacture antibodies, whose role is to fight infections.

Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is an abnormal proliferation of lymphoid stem cells blocked at an early stage of differentiation. ALL develops rapidly, within a few days or a few weeks of the first symptoms. Acute lymphoblastic leukemia (ALL) accounts for approximately 20% of adult leukemias and more than one third of cancers in children.

Chronic lymphocytic leukemia

Chronic lymphoid leukemia (CLL) is a disease of the blood characterized by an excess of white blood cells in the blood and which develops slowly (chronic). In the case of chronic lymphoid leukemia, the B lymphocytes produced by the bone marrow accumulate in the blood, the ganglia, the spleen and the bone marrow, instead of dying within a few days or months to be replaced by others. It is the most common leukemia, affecting mainly people aged over 50.

Acute myeloid leukemia

Acute myeloid leukemia (AML) is due to the proliferation of blasts – cells that give rise to white blood cells that have become tumoral – in the bone marrow which can then no longer ensure the production of healthy blood cells. The frequency of acute myeloid leukemias (AMLs) increases after the age of 40, the average age being 65.

Multiple myeloma

Multiple myeloma, more commonly known as Kahler’s disease, is a disorder of the bone marrow caused by an uncontrolled proliferation of plasmocytes (blood cells of the family of white blood cells) specialized in the production of antibodies. In Kahler’s disease, the plasmocytes that proliferate all come from one abnormal plasmocyte. Multiple myeloma is a relatively rare cancer. This disease affects mainly people aged over 60.

T cell acute lymphoblastic leukemias

T cell acute lymphoblastic leukemias (T-ALLs) are aggressive hematologic tumors resulting from the malignant transformation of T cell progenitors.

Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive hematological malignancy derived from plasmacytoid dendritic cell precursors.

 

Solid tumors
Cancerous solid tumors, identifiable as a localized mass of cells, differ from cancers of the blood cells, such as leukemias, whose cancerous cells circulate in the blood or lymph and are dispersed into the body. The majority of cancers are solid tumors. Two types of solid tumor are differentiated:
• carcinomas arise from epithelial cells (skin, mucosa, glands).
• sarcomas, less common, arise from cells of the connective tissue (known as “supporting” tissue).

Pancreatic cancer

Pancreatic cancer is characterized by an anarchic proliferation of cells which forms a mass of tissue, i.e. a tumor, in the pancreas. Adenocarcinoma, which accounts for 95% of these tumors, is situated in the exocrine cells of the pancreas and is the most common type of pancreatic cancer. Although it is relatively rare, pancreatic cancer is one of the most formidable.

Non-small-cell lung cancer

Non-small cell lung cancer Non-small cell lung cancer (NSCLC) is an epithelial tumor of the lung. The most common forms of NSCLC are epidermoid carcinoma, large-cell carcinoma and adenocarcinoma, but there are other rarer forms. Non-small cell lung cancer (NSCLC) accounts for between 80 and 85% of lung cancers.

Glioblastoma

Multiform glioblastoma is a brain tumor which will affect the astrocytes, cells of the central nervous system. It is the most common brain cancer in adults and the most aggressive.

Victim blaming

Victim blaming (or blaming the victim) is holding the victim (s) of a crime, an accident, or any type of abusive maltreatment to be entirely or partially responsible for the transgressions committed against them. Victim-blaming has traditionally emerged especially in racist and sexist forms. It is also about holding individuals responsible for their own personal distress or difficulties instead of attributing responsibility to the transgressors who caused it.

 History of the concept

The phrase “Blaming the victim” was coined by William Ryan in his 1976 classic book of the same title, as a critique of Daniel Patrick Moynihan’s 1965 work The Negro Family: The Case for National Action, usually simply referred to as the Moynihan Report. Moynihan’s book summarized his theories about ghetto formation and intergenerational poverty. Ryan’s critique cast the Moynihan theories as subtle (and not so subtle) attempts to divert responsibility for poverty from social structural factors to the behaviors and cultural patterns of the poor. The phrase was quickly adopted by advocates for crime victims, in particular rape victims accused of abetting their victimization, although this usage is conceptually distinct from the sociological critique developed by Ryan.

Main article: Just-world phenomenon

It has been proposed that one cause of victim-blaming is the “just-world phenomenon”. People who believe that the world has to be fair may find it hard or impossible to accept a situation in which a person is unfairly and badly hurt. This leads to a sense that, somehow, the victim must have surely done ‘something’ to deserve their fate. Another theory entails the need to protect one’s own sense of invulnerability. This inspires people to believe that rape only happens to those who deserve or provoke the assault (Schneider et al., 1994). This is a way of feeling safer. If the potential victim avoids the behaviors of the past victims, then they themselves will remain safe and feel less vulnerable. A global survey of attitudes toward sexual violence by the Global Forum for Health Research shows that victim-blaming concepts are at least partially accepted in many countries. In some countries, victim-blaming is more common, and women who have been raped are sometimes deemed to have behaved improperly. Often, these are countries where there is a significant social divide between the freedoms and status afforded to men and women.

This idea dates from ancient times: the biblical Book of Job offers a refutation of the Just World Hypothesis, in which the main character, Job, maintains his faith through calamity after calamity, all of which are explicitly unrelated to his behavior, which remains devout.

Supporters of this view (once referred to as “Job’s comforters”) must perforce accept that to do otherwise would require them to give up their belief in a just world, and require them to believe in a world where bad things – such as poverty, rape, starvation, and murder – can happen to good men and women. Though a form of attribution error, this incorrect attribution differs from the “Fundamental Attribution Error” principally in its focus. Both concepts however center around a tendency to ignore situational contributors in favor of supposed internal failings on part of the subject being judged. In the Just-World Hypothesis the subject’s actions are not being scrutinized, but their situation; whereas those making the Fundamental Attribution Error tend to focus primarily on attributing actions to personal qualities and ignoring situational causes. Crimes or other events that create a victim give opportunity for both attribution errors – in blaming the victim for “allowing” themselves to be victimized by crime as well as the inability to cope afterwards. Despite their frequent simultaneity though, they remain two distinct attribution errors.

 Secondary victimization

Rape is especially stigmatizing in cultures with strong customs and taboos regarding sex and sexuality. For example, a rape victim (especially one who was previously a virgin) may be viewed by society as being “damaged.” Victims in these cultures may suffer isolation, be disowned by friends and family, be prohibited from marrying, be divorced if already married, or even killed. This phenomenon is known as secondary victimization.

Secondary victimization is the re-traumatization of the sexual assault, abuse, or rape victim through the responses of individuals and institutions. Types of secondary victimization include victim blaming and inappropriate post-assault behavior or language by medical personnel or other organizations with which the victim has contact. Secondary victimization is especially common in cases of drug-facilitated, acquaintance, military sexual trauma and statutory rape.

 Rape Shield Laws

In the United States, rape is unique in that it is the only crime in which there are statutory protections designed in favor of the accuser (known as “rape shield laws”). These were enacted in response to the common defense tactic of “putting the accuser on trial”. Typical rape shield laws prohibit cross-examination of the accuser (alleged victim) with respect to certain issues, such as his or her prior sexual history, or the manner in which he or she was dressed at the time of the rape. Most states and the federal rules, however, provide exceptions to the rape shield law where evidence of prior sexual history is used to provide an alternative explanation for physical evidence, where the defendant and the alleged victim had a prior consensual sexual relationship, and where exclusion of evidence would violate the defendant’s constitutional rights.

Suggest ways to monitor cancer care coordination and measurement

cancer measurePlease email motherhealth@gmail.com for any suggestions related to cancer care coordination and measurement.

The rapid adoption of Electronic Health Records (EHRs), increased patient engagement, rapid adoption of mobile technology, and shift to value-based care have contributed to an increased use of health information technology (IT) to improve quality and outcomes of patient care.

There is a need for more coordination in cancer care due to the growing complexity of cancer treatment and the increase in cancer survivors that need better coordination within and across clinical teams and care settings. Poorly coordinated care leads to avoidable hospital readmissions, preventable medical errors, harm to patients and higher costs. Care coordination strategies share seven essential tasks: assess patient, develop care plan, identify participants and specify roles, communicate with patients and other participants, execute care plan, monitor and adjust care, and evaluate outcomes. Health IT plays an important role in care coordination in diverse organizations like Kaiser Permanente and the VA.

The measurement process for care coordination is changing from the laborious process of manual chart reviews to EHR-based measurement.

Care Coordination is a multi-dimensional concept that encompasses many facets of healthcare organization and delivery. Because poorly coordinated care regularly leads to unnecessary suffering for patients, as well as avoidable readmissions and emergency department visits, increased medical errors, and higher costs, coordination of care is increasingly recognized as critical for improvement of patient outcomes and the success of healthcare systems. In Phase 3 of this project, measures submitted focused on key areas of emergency department transfers, medication reconciliation and timely transitions. This report focuses on the evaluation of one newly submitted and four care coordination measures undergoing maintenance review for suitability as voluntary consensus standards.

Example of what will be monitored: medication and medication reconciliation

Medication Reconciliation: Number of Unintentional Medication Discrepancies per Patient

Description: This measure assesses the actual quality of the medication reconciliation process by identifying errors in admission and discharge medication orders due to problems with the medication reconciliation process. The target population is any hospitalized adul

Numerator Statement: For each sampled inpatient in the denominator, the total number of unintentional medication discrepancies in admission orders plus the total number of unintentional medication discrepancies in discharge orders.

Denominator Statement: The patient denominator includes a random sample of all potential adults admitted to the hospital. Our recommendation is that 25 patients are sampled per month, or approximately 1 patient per weekday.

So, for example, if among those 25 patients, 75 unin

Exclusions: Patients that are discharged or expire before a gold standard medication list can be obtained.

Adjustment/Stratification:

Level of Analysis: Facility

Setting of Care: Hospital/Acute Care Facility

Type of Measure: Outcome

 

How we can help with VA Health Care?

Two trend lines in veterans’ health care are not encouraging.

Demand for Department of Veterans Affairs (VA) services is going up, but so are losses among the agency’s health-care providers.

Annual VA outpatient medical appointments rose by 20 percent, or 17.1 million visits from fiscal 2011 through 2015, according to a new Government Accountability Office report.

But also increasing during that period was the number of staffers in five critical occupations who left the agency. In 2011, 5,897 physicians, registered nurses, physician assistants, psychologists and physical therapists said goodbye. By 2015, that number had grown to 7,734. The rate of loss rose from 7.3 percent to 8.2 percent. The GAO said similar problems affect other health-care organizations because of national shortages and increased competition for clinical employees.

“These staffing shortages directly impact patient care and makes the work of these dedicated employees even more difficult,” said J. David Cox Sr., president of the American Federation of Government Employees, which represents VA staffers.

VA, however, released a flurry statistics to show service is good. Among them, in May, 96.7 percent of appointments were within one month “of the clinically indicated or Veteran’s preferred date,” 85.6 percent were within one week and 21.6 percent were the same-day.

“Improving VHA’s (Veterans Health Administration) ability to forecast, recruit, and retain a workforce continues to be a priority,” the department wrote in a response included in the GAO report.

VA is trying to improve staffing levels with various initiatives. Among other things, it has increased pay for certain health professionals “to close the pay gap with the private sector and to make VA an employer of choice,” according to an agency statement. “With more competitive salaries, VA will be better positioned to retain and hire more health-care providers to care for veterans.”

Breaking down the numbers, GAO found that 28 percent linked their departures to issues involving advancement and 21 percent to dissatisfaction with aspects of the work. “Voluntary resignations and retirements accounted for 84 percent of VHA’s losses from the 10 occupations with the highest loss rates annually from fiscal year 2011 through fiscal year 2015,” according to the report.

The good news is that nearly two-thirds were generally satisfied with their jobs.

Paralyzed Veterans of America’s (PVA) Executive Director Sherman Gillums Jr. said the report echoes what his organization has been saying, particularly about nursing shortages.

“Nurse staffing directly impacts the number of available operating beds for paralyzed veterans requiring initial rehabilitation, acute care, and annual evaluations. Because of under-budgeting and inadequate staffing, VA was forced to use excessive overtime hours and flawed staffing methodologies as band aids to make up for a problem that required more serious intervention,” he said. “This had led to costly turnover and low morale among staff, not to mention artificially suppressed demand due to open but unstaffed beds, all of which render care less than optimal.”

PVA and VA have worked on a new staffing formula that calculates staff needed for patients with severe disabilities. “We hope to see it implemented sooner rather than later,” Gillums added.

In addition to the national shortages in these occupations, VA also has to overcome the stigma associated with the headline grabbing scandal over the coverup of long patient wait times that erupted two years ago. Staffing shortages apparently contributed to the long waits, then the coverup tarnished the agency’s reputation, which probably didn’t help with recruitment.

“The GAO report points out what DAV (Disabled American Veterans) has been saying for years,” said Garry Augustine, executive director of DAV’s Washington headquarters. “The primary reason for veterans’ access problems and waiting lists is there are not enough doctors, nurses and other health-care providers to meet the demand.”

Sen. Richard Blumenthal (D-Conn.) said he requested the GAO report because “understanding the needs of VA’s workforce is absolutely fundamental to ensuring the Department is able to meet growing demands for its services. It’s simple: a VA that is able to attract and retain good employees will also be able to provide continuous services and the highest quality care.”

Please comment and email motherhealth@gmail.com for ways that we can help with the VA Health Care?

Sample suggestions:

  • Motherhealth mobile health application for VA patients, integrated care, accessible video chat with doctors, advice nurse on video chat, matching of care providers, curated health info, volunteers and more

What is a psychopath?

Psychopathy (/saɪˈkɒpəθi/), also known as sociopathy (/soʊsiˈɒpəθi/), is traditionally defined as a personality disorder[1] characterized by persistent antisocial behavior, impaired empathy and remorse, and bold, disinhibited, egotistical traits. Different conceptions of psychopathy have been used throughout history that are only partly overlapping and sometimes appear contradictory.[2]

Hervey M. Cleckley, an American psychiatrist, influenced the initial diagnostic criteria for antisocial personality reaction/disturbance in the Diagnostic and Statistical Manual of Mental Disorders (DSM), as did American psychologist George E. Partridge.[3] The DSM and International Classification of Diseases (ICD) subsequently introduced the diagnoses of antisocial personality disorder (ASPD) and dissocial personality disorder respectively, stating that these diagnoses have been referred to (or include what is referred to) as psychopathy or sociopathy. Canadian psychologist Robert D. Hare later repopularized the construct of psychopathy in criminology with his Psychopathy Checklist.[2][4][5][6][7]

Although no psychiatric or psychological organization has sanctioned a diagnosis titled “psychopathy”, assessments of psychopathic characteristics are widely used in criminal justice settings in some nations, and may have important consequences for individuals. The study of psychopathy is an active field of research, and the term is also used by the general public, in popular press, and in fictional portrayals.[7][8] While the term is often employed in common usage along with the related but distinct “crazy”, “insane” and “mentally ill”, criminal psychology researcher Robert Hare stresses that a clear distinction is known among clinicians and researchers between psychopathic and psychotic individuals: “Psychopaths are not disoriented or out of touch with reality, nor do they experience the delusions, hallucinations, or intense subjective distress that characterize most other mental disorders. Unlike psychotic individuals, psychopaths are rational and aware of what they are doing and why. Their behavior is the result of choice, freely exercised.

Source: Wiki

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What motivates children to eat healthy

By Ana Swanson

In a study published in the journal Health Economics in January, researchers carried out a field experiment to try to motivate 8,000 children in different schools to eat healthier. They found that giving the students a small incentive for eating healthy — in this case, a 25 cent token the kids could spend at the school store, carnival or book fair — doubled the fraction of kids eating at least one serving of fruits or vegetables.

The researchers also found that the effects lingered after the experiment ended, though they did subside somewhat. Two months after the end of the experiment, kids who had been rewarded for their health behavior for a period of five weeks were still eating 44 percent more fruit and vegetables than they had before the experiment begun.

The authors argue that the study provides evidence that short-run incentives can help form lasting behaviors and that longer periods of “interventions” are more effective at changing behavior than shorter ones.

There’s an obvious downside to these practices. Psychological studies have shown that, while external rewards like bribes are effective at getting people to adopt certain behaviors, they can undermine what’s called intrinsic motivation — a person’s internal drive to do a task, for example because it makes them feel more autonomous or competent.

In a 1999 analysis of 128 previous studies, researchers found that giving people rewards did significantly reduce their motivation to pursue the activity when they were not given a reward. In simpler terms that are probably obvious to any parent — bribing kids can spoil them.

Even when this is true, however, there’s often another force at work that may be even more important in changing people’s behaviors in the long-term: healthy life habits. Once people do something over and over again, it can become a subconscious, almost involuntary, inclination. And recent research suggests that those healthy habits have more staying power than the incentive of a bribe or reward.

Habits are powerful things. Most people have certain cues — like certain emotions, places, friends or times of day — that trigger a powerful urge to do a habit, whether it biting nails, smoking a cigarette, or eating a cookie. But habits can also be incredibly useful, if people can harness their power to shake bad behaviors in the longer run.

Another study of more than 1,500 kids in Chicago published in 2014, which was the subject of a Freakonomics podcast, supports the idea that they can. By giving kids who ate a healthy a small reward — a pen, a rubber bracelet or a little plastic trophy — the researchers raised the proportion of children who chose a healthy snack from 17 percent to about 75 percent. But when the researchers stopped doling out the rewards, they found that more kids continued to choose the healthy option — suggesting that intervention might have helped to form a healthy habit.

The study included some other interesting findings: For one, education alone wasn’t enough to change kids’ behaviors. After extolling the virtues of eating healthy, about 80 percent of kids still chose a cookie over fruit. But the researchers found that the combination of education and incentives was powerful.

Past experiments have produced mixed results on how long these effects last, with some finding that beneficial effects taper off relatively quickly. But in some cases, getting over the initial hurdle to change one’s behavior is enough. Just a brief change of habit can convince people that they actually do like the taste of squash, that they like the way exercise makes them feel, or that they have the willpower to resist cigarettes. In one 2009 study, for example, incentives helped some adults quit smoking for 12 months, and that period of cessation made it easier for people to stay smoke-free in the longer term, even without incentives.

In all of these studies, the rewards didn’t always work. For adults as well as kids, habits can be extremely hard to change. But offering an incentive appears to be the most effective way to change them. That’s because people are psychologically inclined to favor short-term rewards, like goofing off or eating tasty food, over long-term ones, like being healthy or saving for retirement. Giving people rewards for healthy behaviors just helps align their short-term incentives with their long-term ones.

Among parents, a lot of the debate over how to influence behavior comes down to exactly what you do and how you do it. Obviously, it may be preferable to just establish eating fruit and vegetables as normal behavior, and not give kids another option. But if that doesn’t work, many parents feel that offering their kids a trip to the zoo or the chance to pick the movie that night is a healthy way to reward good behavior. Others feel that, while giving a kid a dollar per carrot is a slippery slope, rewarding hard work with an allowance or a sought-after possession teaches kids what it’s like to work and have a job.

The debate often comes down to the language people use — whether they call it bribery, a reward or an incentive.

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