The announcement that he intended to come to New York produced a huge protest. Sixty-five noted holocaust and genocide scholars sent a letter to President Obama, urging him to hand the Sudanese president over to the International Criminal Court to be prosecuted for war crimes and crimes against humanity, including: We humans have a long history of doing violence to one another. And those of us who do not have blood on our hands have a remarkable knack for averting our gaze.
Workflow for urinary biomarker development studies. Briefly, discovery is conceived as involving large-scale quantification of urinary proteins in a few very-well-defined clinical cases and an equal number of appropriate controls. The output is a list of candidate biomarkers.
Validation is a clinical trial involving many more patients than the few enrolled in discovery studies, using appropriate assays for each of the candidate biomarkers. The expected output is a statement of the likely specificity and sensitivity of the assays with regard to the clinical decision-making task being addressed.
The implementation phase involves assay development, regulatory approvals Food and Drug Administration and otherwisemanufacturing, and marketing. Implementation is probably best carried out in the private sector.
It is not self-evident that the availability of a urinary protein biomarker for any given clinical entity will bring benefit. Thus, biomarker development should be driven by needs defined by clinical investigators rather than by the availability of the technology for carrying out protein mass spectrometry.
What types of urinary biomarkers might prove useful? Urinary protein biomarker assays can potentially aid diagnosis, allow assessment of prognosis, guide the choice of therapeutic regimen, or provide feedback about response to therapy.
An example is identification of protein biomarkers that would help with therapeutic decisions in the setting of a sudden rise in serum creatinine concentration in patients with a renal allograft. Hypothetically, such a rise could be due to graft rejection or tubular injury.
Urinary protein biomarker assays that distinguish these two entities could allow interventions while the clinician is waiting for biopsy results and could potentially provide information complementary to biopsy data.
The practicality of any hypothetical urine protein biomarker can be addressed a priori on the basis of calculations using likely sensitivity and specificity measures.
Instead, a battery of markers, each with a limited specificity, may be required to get the overall high level of specificity needed. Therefore, the aim of discovery studies in patients with clear cell carcinoma would be to identify multiple candidate biomarkers to be used in tandem.
Therefore, techniques that were state of the art 3 yr ago may be substandard today. Newer instruments are capable of much better mass resolution and therefore greater certainty in protein identification, thereby reducing false-positive results. It will pay, therefore, for clinical investigators planning urinary biomarker development studies to collaborate with leaders in the field of protein mass spectrometry to ensure use of the best possible technology.
Explicit identification of specific proteins should be achievable with contemporary mass spectrometers, and it should not be necessary to settle for identification of nondescript mass-to-charge ratio peaks of unknown proteins.
A proposed biomarker for vasopressin action in the kidney is the water channel aquaporin 2 AQP2. Yet, in some cases, urinary AQP2 excretion rate does not correlate with vasopressin action, 12 and there are important theoretical reasons to expect that AQP2 abundance in urine will not correlate with antidiuretic mechanisms.
A particularly desirable aspect of this approach is the possibility of normalization by total AQP2, allowing this measurement to be carried out in spot urine samples.
Measurement of other posttranslational modifications, such as ubiquitination, may likewise be useful. Finally, unique proteolytic fragments of particular proteins may be of diagnostic value, particularly in identification of biomarkers for various cancers that secrete characteristic proteases.
It is anticipated that many, if not most, candidate biomarkers that arise from discovery studies will be false-positive results or eventually shown to have very limited predictive value.
Ultimately, well-designed validation studies will be what make or break the emerging field of urinary protein biomarkers discovery. The objective of such a clinical trial is to ascertain how well a given protein biomarker or battery of biomarkers predicts the presence of some clinical characteristic important for clinical decision-making.
Thus, it should define the likelihood of a false-positive prediction specificity and of a false-negative prediction sensitivity when a proposed biomarker assay is used in the general population.
In contrast, confirmation of discovery results obtained by protein mass spectrometry addresses a different issue: Is the measurement obtained in a mass spectrometry experiment reproducible?Get an answer for 'Looking for quotes on disconnectedness, dehumanization, alienation, and dislocation in chapter 7.' and find homework help for other All Quiet on the Western Front questions at.
A tip from a school friend led police on a frantic four-day search that ended unusually happily: the police discovered not only Ben, but another boy as well—year-old Shawn Hornbeck, who, four years earlier, had disappeared while riding his bike at the age of title = "Overlooking others: Dehumanization by comission and omission", abstract = "Dehumanization, the denial of fundamentally human capacities to others, has contributed to largescale intergroup conflict and violence, ranging from the Holocaust, to American slavery, to .
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A century later, commercial aircraft could carry passengers at speeds approaching miles per hour, a rate of progress of only about 2% per year.
By contrast, progress today comes rapidly. Consider the numbers for information storage density in computer memory.