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Examinatien Date

Start

B2RQ7 Research Q7 April 11 th 2018 13:00 h

Radboud

Your are allowed to use a calculator of the type Casio FX-82MS.

The questions must be answered in English. lf you cannot remember a specific English term, you can use the Dutch term.

After finishing the exam, you can take this examination set a long with you.

Please hand in the OTHER part (the answering form) to the supervisor.

During the exam you have access on a computer to these books:

Casarett & Doull's Essentials of Toxicology (3e)

GENERAL INSTRUCTIONS:

Th is exam consists of 8 open questions.

The available time is 2 hours.

You are allowed to use scrap paper that wilt be handed out. Do not use the scrap paper for your answers and do not hand it over to the supervisor.

Check if your examinatien set is complete.

Please write your name and student number on each page of the answering form.

Write your answers on the answering farm In the open space below the questions.

Raad the questlons carefully befare phrasing your answers.

Be concise and complete in your answers.

lf necessary you can a lso u se the backside of the pages.

Refrain trom using abbreviations in your answers, and write legibly (illegible answers are considered incorrect).

Please do not use a pencil.

The use of audiovisual and technica! devices is not allowed, unless it is mentioned explicitly elsewhere on this page. Any inappropriate use of such equipment is regardedas fraud.

Except tor the exam farms, some loose wrltlng material, your student and registration card your table should be empty. No boxes or cases are allowed.

After finishing the exam, please hand the answerlng form to the supervisor. lf you have

comments about the questions we refer you to the hyperlink of the digital comment form that is included in your "studenten webdossier" below "toetsen".

SUCCESS!

ATTENTION 11

(2)

Name: Studentnummer:

General question Question 1 (1 0 pts)

The Health Council provides advice to the government regarding pubtic health matters.

This involves complex decision making based on factual and normative (un)certainties.

The text below, which is taken from the work programme of 2018, describes a request for advice from the Minister of Health and Welfare and Sports.

Organ donation following euthanasia: protocol for determining death

In recent years there has been an increase in the number of organ

donations fol/owing euthanasia in the Netherlands. This development requires a responsible combination of two procedures, name/y the

procedure for euthanasia and the procedure for postmortal organ

donation. At the request of the Minister of Health and Welfare and Sport a working group of the Dutch Transplant Foundation has drawn up aJl_injfial version of a guidelif]§_On how that combination procedure can be

implemenled with maximum care and safeguards. In this context there is a .n..eed for.a specific orotoGD.l to delermine death The Health Council did not

consider this issue in the advisory report entitled 'Determining death in postmortal organ donation'

(2015113(R)).

The Minister has now submitted an explicit request for advice to the Council so that a /ega/ basis can be created.

The table below allows the classification of such a request based on certainty pertaining normative criteria and the knowledge about the underlying health issue.

HIGH consensus on normative criteria LOW consensus on normative criteria

HIGH certainty on knowied ge

A c

Whic

h� '1}.

,

,2�

or

Hfq;}

this table provides the best classification of the issue of determining death in the context of organ donation after euthanasia? (4 pts)

Explain your answer with one argument regarding the certainty of knowledge and one argument regarding the consensus on normative criteria surrounding this issue. (6 pts)

Research exam Q7 Biomedical Sciences (2017 -2018) - April 11, 2018 2

(3)

Name: Studentnummer:

Question 3 (1 0 pts)

Rubella is a mild childhood disease. Humans are the only host. The virus is transmitted by the respiratory route and replicates in the nasal tissue. The biggest problem is that

infection during early pregnancy may cause death of the fetus or Congenital Rubella

Syndrome, with severe birth defects in eyes, heart and brain. The critica! vaccine coverage for Rubella is 84%.

Rubella - United States, 1966-2001

*

- Rubella -+-CRS

70000 80

60000 70

U) 50000 60

IV VI

VI 50 IV

(U U)

0 40000 C'!S

(U 40 (.)

CU 30000 U)

...Q 30 Q::

::J 20000 (.)

Q:: 20

10000 10

0 0

1966 1970 1974 1978 1982 1986 1990 1994 1998

*2001 provisional data

a. In the figure above you see the incidence in Rubella and Congenital Rubella syndrome (CRS) in the United States. After Rubella vaccination started in 1969 in the United States, a significant decrease in the incidence of Rubella was seen. Epp�R-iflerease-in con enital rubella syndrome can be seen if the critica I vaccine coverage is not reached. (4 pts)

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sp �d

-0

OL-t-t ir:Jrt?.

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vo,-r ,.{(\)

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rJ I • .

(4)

Name: Studentnummer:

11 I I [ I [ I 11

Question 4 ( 1 0 pts)

A correlate of proteetion is not established thus far for may vaccines and diseases, but knowing these would have major advantages.

a. Explain what is meant by a correlate of protection. (3 pts)

b. Name an advantage of the use of a correlate of proteetion when testing a vaccine and explain how this can be used. (3 pts)

c. Describe how a correlate of proteetion can be established for a vaccine in human use.

(4 pts)

Research exam Q7 Biomedical Sciences (2017 -2018) -April 11, 2018 6

(5)

Name: Studentnummer:

11 I I I I I I Jl

Question 6 (15 points)

Formaldehyde in anatomy pathology

Formaldehyde is a small molecule (CH20) with strong irritating and sensitizing properties. lt is used in 3-4 % dilutions in water (formalin), as fixative and preservative in anatomy and pathology departments of hospitals and universities. Exposure to formaldehyde can lead to respiratory and s..kin ensitization. A suggested mechanism for the observed cytogenetic damage is

related to enotoxicity, including the formation of protein and DNA crosslinks. There is sufficient evidence for carcinogenicity of nasal tis.sues but for tumors of internal organs, more specifically of the hematological malignancies (leukemia's), the evidence is rated as 'limited' by the WHO. Overall, formaldehyde is classified as a carcinogen to humans. The available human data are� sufficient to e a_ reliable judgement on the reproductive

toxicity of formaldehyde exposures. ---

a. Which three general approaches can be applied to characterize the exposure to formaldehyde? (3 pts)

b. What are the �most important sourees of

in a quantitative risk assessment for reproduetion toxic endpoints? (3 pts)

t Y\A {'__,(

hlqh �(ow

c. Which factors will determine the risk during anatomy classes? Provide three environmental factors and three host factors. (6pts)

['�

1

qvt.ciP ./ �i (lQ_,f l

C 5

H;mp

(

pr

1

Ut?AtJ·{.

d. Based on the information provided, how would you describe the hazard of formaldehyde in a communication to the students who follow anatomy classes involving formaline-immersed preparations? Use 2-3 short sentences. (3 points)

(6)

Name: Studentnummer:

Question 8 (16 points)

One of the diseases that is NOT included in the newborn screening in the Netherlands is Duchenne muscular dystrophy (DMD), a progressive X-linked neuromuscular disorder. lt has an estimated worldwide incidence of 1 :3500 111ale births. Currently, there are..ll2.

cu t" treatments and the m.ecm e o · s· is-5 years. Mothers often are pregnant

again before the diagnosis of DMD in the newborn. In Wales, United Kingdom, a screening programme was introduced in 1990. Newborn bloodspots were collected routinely as part of the Wales newborn screening programme. During a 2 - ear eriod 343

QO

children were screened using a bloodspot creatine kinase (CK) assay. A total of j45 cases had a r..ajsecLC cf ·

(Z25

U/1). The final diagnosis after a positive screening test was made after 6-8 weeks of follow-up.

7,�

cases had a norma!..§,erum CK, indicating absence of DMD, while.B6_cg§es

an elevated serum CK, leading to a diagnosis of DMD by

genotyping or muscle biopsy studies. Th is long-term study has so far identified

��es of

DMD that had a negative CK assay.

a. What is the programme sensitivity, specificity, predictive value of a positive test (PV+), and the detection rate? Please write also down how you calculated the measures.(1 0 pts)

o

+

CJ

oco (9 p U �r-

::

Y 6 I

'S..ef!) 60. i� � �

spec 7,

b. Discuss one a vantage and one disadvantage of including DMD screening in the newborn screening. (4 pts)

c. The incidence of DMD in Wales was 1:5136 during the period that DMD testing was included in the NBS screening programme. Before DMD screening was included in the newborn screening programme in Wales it was 1 :4046. Give an explanation for this drop in incidence. (2 pts)

...

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Research exam Q7 Biomedical Sciences (2017 -2018) -April 11, 2018 10

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