Massachusetts has made a strong showing in a $348 million federal grant program that encourages biomedical researchers to engage in high-risk projects with the potential to accelerate the translation of research discoveries into treatments.

Eleven of 42 Transformational R01 grants are flowing to scientists in the state and 12 of 55 New Innovator award winners are based here. One of 18 Pioneer Award recipients is from Massachusetts. All three programs from the National Institutes of Health are designed to spur exploration that may have been deemed too risky in past rounds.

University of Massachusetts Medical School scientists who began human testing of an AIDS vaccine five years ago have won two five-year grants totaling $18 million to further their research.

Dr. Shan Lu, professor of medicine and biochemistry and molecular pharmacology at UMass and a specialist in vaccine development, will lead both projects. One seeks to develop protective antibodies that will target the virus where it binds to human immune cells and the other will look further into the cocktail of viral antigens they tested in phase 1 human trials. The funding comes from the National Institute of Allergy and Infectious Diseases.

Creating an AIDS vaccine has been seen as an almost insurmountable challenge, given the poor results to date. Last week some encouraging news emerged from a massive trial in Thailand where a vaccine met limited success.

Patients who don't take their medications as prescribed pay a price in poorer health, more frequent hospitalizations, and a higher risk of death. They also incur up to $290 billion annually in increased medical costs, according to a Boston-based health policy group that urges making the issue part of the national debate on overhauling health care.

A report released this week by the New England Healthcare Institute updates a 2001 analysis of the costs of what is called poor patient medication adherence. The new report is based on seven systematic reviews of the medical literature as well as interviews with 16 health care organizations, insurers, drug makers, and technology companies. The work was paid for by this group of stakeholders, but the report was written independently of them, institute executive director Valerie Fleishman said.

"Much of the discussion in health reform today is really about providing better outcomes for patients, and ultimately better health and medication adherence is a fundamental missing link to better outcomes," Fleishman said in an interview. "We believe that it's critical that adherence be woven into the fabric of the health reform debate."

The four medical schools in Massachusetts earned passing grades for their conflict-of-interest policies in a new report card issued by a medical student's organization, including a jump from F to B for Harvard and a change from I to D for Tufts.

The American Medical Student Association's PharmFree Scorecard gave Bs to Boston University School of Medicine, Harvard Medical School, and the University of Massachusetts Medical School for their guidelines governing interactions between pharmaceutical companies and medical students and faculty members. Tufts University School of Medicine got a D. Last year's grade was and I for "in process" while the school was working on its policy.

Four noted scientists will lead one of three programs at the state's medical school that form a key part of the Massachusetts life sciences initiative.

The RNA Therapeutics Institute, part of the Advanced Therapeutics Cluster at University of Massachusetts Medical School in Worcester, will be headed by Nobel laureate Craig C. Mello and his colleagues Melissa J. Moore, Phillip D. Zamore, and Victor Ambros. The team will lead efforts to explore how RNA interference, a gene-silencing mechanism, might prevent or treat disease.

The institute, along with the Gene Therapy Center and the Center for Stem Cell Biology and Regenerative Medicine, are part of a statewide effort to boost the life sciences. Guangping Gao was named director of the Gene Therapy Center in March. The medical school is still searching for a leader of the stem cell center.

Harvard Medical School is the top research medical school in the United States, according to annual rankings compiled by US News & World Report.

Boston University School of Medicine ranked 35th, Tufts University School of Medicine placed 45th, and University of Massachusetts Medical School came in 48th out of 126 US medical schools and 20 schools of osteopathic medicine.

In primary care, UMass ranked 7th, Harvard was 15th, and Tufts 40th. BU was among those not ranked in primary care.

Massachusetts ranks first in the number of early-career scientists to win prestigious grants in a national program designed to encourage innovation when research dollars are scarce.

Ten researchers -- from Harvard, Massachusetts General Hospital, MIT, and University of Massachusetts Medical School -- are among 50 scientists who have won six-year appointments to the Howard Hughes Medical Institute. California ranked second, with eight winners.

The $200 million Early Career Scientist program pays the salaries of the scientists and gives them each $1.5 million to fund their research.

The program was created last year to help scientists establish their own research programs amid a tighter funding climate that was harsh for people at the start of their independent careers. Candidates must have led their own laboratories for two to six years. A total of 2,000 applicants sought the appointments, which support the scientists at their home institutions.

Fourth-year medical students chose primary care today in somewhat larger numbers than in recent years on the day future MDs across the country learned where they will spend the next phase of their medical training.

In Massachusetts, the percentage of students who picked primary care -- which includes family practice and pediatrics -- stayed about the same or grew at Boston University School of Medicine, Tufts University School of Medicine, and University of Massachusetts Medical School. At Harvard Medical School the percentage dipped slightly, part of an up-and-down pattern over the past 10 years.

Here are the primary care numbers for this year (and last):

BU: 26 percent of 105 students (17 percent last year)
Harvard: 10 percent of 165 students (12 percent last year)
Tufts: 18 percent percent of 104 students (17 percent last year)
UMass: 39 percent of 100 students (35 percent last year)

Some students who were matched to internal medicine residencies may later enter primary care, so there may be more primary care doctors in the pipeline than it would appear.

Primary care has been losing ground for many years to more lucrative specialties, including dermatology and surgery. As shortages of primary care doctors have deepened, physicians have faulted a healthcare system that pays more for procedures than for care that primary care doctors provide.

At Harvard, 8 percent of fourth-year students picked dermatology, up from 3 percent last year but the same as in 2003. That puts dermatology ahead of the 7 percent of students entering residencies in pediatrics this year, but the opposite was true for the last nine years. Pediatrics and internal medicine have been the top two choices since 2000.

"My students keep picking what are claimed to be the lowest-paid specialties: internal medicine and pediatrics," said Dr. Nancy Oriol, dean of students at Harvard Medical School. "I have a hard time seeing anything having an impact on their choices."

Students applied to programs in July, before the current economic downturn that began last fall. But the money owed for student loans has been a concern for the last several years, said Dr. Amy Kuhlik, dean of student affairs Tufts.

"We know debt level impacts student choices," she said, citing national surveys. "About 30 percent of students say it impacts their choice of field. But generally speaking I think they feel secure in the fact they are going into residency and secure they will have jobs when they get out."

A research group led by Boston scientists has found a gene whose defects cause a familial form of ALS, the devastating neurological disorder better known as Lou Gehrig's disease.

Ten percent of amyotrophic lateral sclerosis cases are inherited. The disease has been traced to only a few gene mutations that lead to the death of nerve cells that send messages to muscles. Most people develop ALS in middle age, becoming progressively weaker and then paralyzed, usually dying of respiratory failure within two to five years. About 30,000 Americans have the disease, according to the ALS Association.

A team from Massachusetts General Hospital, the Broad Institute, MIT, and other institutions write in tomorrow's Science about their discovery of a fourth gene whose 13 mutations caused ALS in a family of Cape Verdean origin. In another Science paper, a group in England reports two more mutations in the same gene that were found in eight British families.

"Every time a new gene like this is found, it illuminates a new pathway for triggering the disease," senior author Dr. Robert H. Brown Jr. said in an interview. "Once one has the gene, one can make a mouse model or cell model for this disease, which should accelerate efforts to find therapies for it."

People are more likely to follow advice to quit smoking or lose weight if they have just been told they have cancer, heart disease, diabetes, or another serious condition, a study shows, spurring a call to doctors to help patients seize the day.

Yale researcher Patricia Keenan analyzed results from a survey of more than 20,000 retired people under age 75 who were overweight and more than 7,000 people of the same age who smoked. People newly diagnosed with stroke, cancer, lung disease, heart disease, or diabetes were more than three times as likely to quit smoking as similar people without a new diagnosis. Overweight people newly diagnosed with lung disease, heart disease, or diabetes lost an average of 2 to 3 pounds more than those who hadn't just been diagnosed.

"The health diagnosis might serve as a cue not only for the patient but also for the physician," Sherry Pagoto and Judith Ockene of the University of Massachusetts Medical School write in an editorial appearing with the article in the Archives of Internal Medicine. "However, the effect of physician advice might only be as good as the availability of supportive services to which patients can be referred."