A general operator expansion is presented for quark and lepton mass matrices in unified theories based on a U(2) flavor symmetry, with breaking parameter of order
V
cb
≈
m
s
/
m
b
≈ √
m
c
/
m
t
. ...While solving the supersymmetric flavor-changing problem, a general form for the Yukawa couplings follows, leading to nine relations among the fermion masses and mixings, five of which are precise. The combination of grand unified and U(2) symmetries provides a symmetry understanding for the anomalously small values of
m
u
/
m
c
and
m
c
/
m
t
. A fit to the fermion mass data leads to a prediction for the angles of the CKM unitarity triangle, which will allow a significant test of these unified U(2) theories. A particular SO(10) model provides a simple realization of the general operator expansion. The lighter generation masses and the non-trivial structure of the CKM matrix are generated from the exchange of a single U(2) doublet of heavy vector generations. This model suggests that
CP is spontaneously broken at the unification scale—in which case there is a further reduction in the number of free parameters.
AbstractBackgroundRabies is a neglected zoonotic disease with a global burden of approximately 59,000 human deaths a year. Once clinical symptoms appear, rabies is almost invariably fatal; however, ...with timely and appropriate post-exposure prophylaxis (PEP) consisting of wound washing, vaccine, and in some cases rabies immunoglobulin (RIG), the disease is almost entirely preventable. Access to PEP is limited in many countries, and when available, is often very expensive. MethodsWe distributed a standardized assessment tool electronically to a convenience sample of 25 low- and middle-income countries in Asia and Africa to collect information on rabies PEP procurement, forecasting, distribution, monitoring and reporting. Information was collected from national rabies focal points, focal points at the World Health Organization (WHO) country offices, and others involved in procurement, logistics and distribution of PEP. Because RIG was limited in availability or unavailable in many countries, the assessment focused on vaccine. Data were collected between January 2017 and May 2018. ResultsWe received responses from key informants in 23 countries: 11 countries in Asia and 12 countries in Africa. In 9 of 23 (39%) countries, rabies vaccine was provided for free in the public sector and was consistently available. In 10 (43%) countries, all or some patients were required to pay for the vaccine in the public sector, with the cost of a single dose ranging from US$ 6.60 to US$ 20/dose. The primary reason for the high cost of the vaccine for patients was a lack of funding at the central level to subsidize vaccine costs. In the remaining 4 (17%) countries, vaccine was provided for free but was often unavailable so patients were required to purchase it instead. The majority of countries used the intramuscular route for vaccine administration and only 5 countries exclusively used the dose-sparing intradermal (ID) route. Half (11/22; 50%) of all countries assessed had a standardized distribution system for PEP, separate from the systems used for routine childhood vaccines, and almost half used separate storage facilities at both central and health facility levels. Approximately half (9/22; 41%) of all countries assessed reported having regular weekly, monthly or quarterly reporting on rabies vaccination. ConclusionsWhile all countries in our assessment had rabies vaccines available in the public sector to some extent, barriers to access include the high cost of the vaccine to the government as well as to patients. Countries should be encouraged to use ID administration as this would provide access to rabies vaccine for many more people with the same number of vaccine vials. In addition, standardized monitoring and reporting of vaccine utilization should be encouraged, in order to improve data on PEP needs.
WHO Expert Consultation on Rabies Organization, World Health
World Health Organization technical report series,
2013
982
eBook, Journal Article
Recenzirano
More than 99% of all human rabies deaths occur in the developing world and although effective and economical control measures are available the disease has not been brought under control throughout ...most of the affected countries. Given that a major factor in the low level of commitment to rabies control is a lack of accurate data on the true public health impact of the disease this report of a WHO Expert Consultation begins by providing new data on the estimated burden of the disease and its distribution in the world. It also reviews recent progress in the classification of rabies viruses rabies pathogenesis and diagnosis rabies pre- and post-exposure prophylaxis the management of rabies patients and canine as well as wildlife rabies prevention and control. _x000D__x000D_ _x000D__x000D_ The information in this report should be considered the most current data on rabies prevention and control and supersedes that of the report of the first WHO Expert Consultation on Rabies published in 2005.
In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause.
We reviewed the medical records of the organ donor and the ...recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice.
The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat.
This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.
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