����JFIFXX�����    $.' ",#(7),01444'9=82<.342  2!!22222222222222222222222222222222222222222222222222����"��4�� ���,�PG"Z_�4�˷����kjز�Z�,F+��_z�,�© �����zh6�٨�ic�fu���#ډb���_�N�?��wQ���5-�~�I���8����TK<5o�Iv-�����k�_U_�����~b�M��d����Ӝ�U�Hh��?]��E�w��Q���k�{��_}qFW7HTՑ��Y��F�?_�'ϔ��_�Ջt��=||I ��6�έ"�����D���/[�k�9���Y�8ds|\���Ҿp6�Ҵ���]��.����6�z<�v��@]�i%��$j��~�g��J>��no����pM[me�i$[����s�o�ᘨ�˸ nɜG-�ĨU�ycP�3.DB�li�;��hj���x7Z^�N�h������N3u{�:j�x�힞��#M&��jL P@_���� P��&��o8������9�����@Sz6�t7#O�ߋ �s}Yf�T���lmr����Z)'N��k�۞p����w\�Tȯ?�8`�O��i{wﭹW�[�r�� ��Q4F�׊���3m&L�=��h3����z~��#�\�l :�F,j@�� ʱ�wQT����8�"kJO���6�֚l����}���R�>ډK���]��y����&����p�}b��;N�1�m�r$�|��7�>e�@B�TM*-iH��g�D�)� E�m�|�ؘbҗ�a��Ҿ����t4���o���G��*oCN�rP���Q��@z,|?W[0�����:�n,jWiE��W��$~/�hp\��?��{(�0���+�Y8rΟ�+����>S-S����VN;�}�s?.����� w�9��˟<���Mq4�Wv'��{)0�1mB��V����W[�����8�/<� �%���wT^�5���b��)iM� pg�N�&ݝ��VO~�q���u���9� ����!��J27����$O-���! �:�%H��� ـ����y�ΠM=t{!S�� oK8������t<����è:a������[�����ա�H���~��w��Qz`�po�^ ����Q��n� �,uu�C�$ ^���,������8�#��:�6��e�|~���!�3�3.�\0��q��o�4`.|� ����y�Q�`~;�d�ׯ,��O�Zw�������`73�v�܋�<���Ȏ�� ـ4k��5�K�a�u�=9Yd��$>x�A�&�� j0� ���vF��� Y�|�y��� ~�6�@c��1vOp�Ig����4��l�OD���L����� R���c���j�_�uX6��3?nk��Wy�f;^*B� ��@�~a�`��Eu������+���6�L��.ü>��}y���}_�O�6�͐�:�YrG�X��kG�����l^w���~㒶sy��Iu�!� W ��X��N�7BV��O��!X�2����wvG�R�f�T#�����t�/?���%8�^�W�aT��G�cL�M���I��(J����1~�8�?aT ���]����AS�E��(��*E}� 2��#I/�׍qz��^t�̔���b�Yz4x���t�){ OH��+(E��A&�N�������XT��o��"�XC��'���)}�J�z�p� ��~5�}�^����+�6����w��c��Q�|Lp�d�H��}�(�.|����k��c4^�"�����Z?ȕ ��a<�L�!039C� �Eu�C�F�Ew�ç ;�n?�*o���B�8�bʝ���'#Rqf���M}7����]����s2tcS{�\icTx;�\��7K���P���ʇ Z O-��~��c>"��?�������P��E��O�8��@�8��G��Q�g�a�Վ���󁶠�䧘��_%#r�>�1�z�a��eb��qcPѵ��n���#L��� =��׀t� L�7�`��V���A{�C:�g���e@�w1 Xp3�c3�ġ����p��M"'-�@n4���fG��B3�DJ�8[Jo�ߐ���gK)ƛ��$���� ���8�3�����+���� �����6�ʻ���� ���S�kI�*KZlT _`���?��K����QK�d����B`�s}�>���`��*�>��,*@J�d�oF*����弝��O}�k��s��]��y�ߘ��c1G�V���<=�7��7����6�q�PT��tXԀ�!9*4�4Tހ3XΛex�46���Y��D ����� �BdemDa����\�_l,��G�/���֌7���Y�](�xTt^%�GE�����4�}bT���ڹ�����;Y)���B�Q��u��>J/J �⮶.�XԄ��j�ݳ�+E��d ��r�5�_D�1 ��o�� �B�x�΢�#���<��W�����8���R6�@g�M�.��� dr�D��>(otU��@x=��~v���2� ӣ�d�oBd��3�eO�6�㣷�����ݜ6��6Y��Qz`��S��{���\P�~z m5{J/L��1������<�e�ͅPu�b�]�ϔ���'������f�b� Zpw��c`"��i���BD@:)ִ�:�]��hv�E�w���T�l��P���"Ju�}��وV J��G6��. J/�Qgl߭�e�����@�z�Zev2u�)]կ�����7x���s�M�-<ɯ�c��r�v�����@��$�ޮ}lk���a���'����>x��O\�ZFu>�����ck#��&:��`�$�ai�>2Δ����l���oF[h��lE�ܺ�Πk:)���`�� $[6�����9�����kOw�\|���8}������ބ:��񶐕��I�A1/�=�2[�,�!��.}gN#�u����b��� ~��݊��}34q����d�E��Lc��$��"�[q�U�硬g^��%B �z���r�pJ�ru%v\h1Y�ne`ǥ:g���pQM~�^�Xi� ��`S�:V29.�P���V�?B�k�� AEvw%�_�9C�Q����wKekPؠ�\�;Io d�{ ߞo�c1eP����\� `����E=���@K<�Y���eڼ�J���w����{av�F�'�M�@/J��+9p���|]�����Iw &`��8���&M�hg��[�{��Xj��%��Ӓ�$��(����ʹN���<>�I���RY���K2�NPlL�ɀ)��&e����B+ь����( � �JTx���_?EZ� }@ 6�U���뙢ط�z��dWI�n` D����噥�[��uV��"�G&Ú����2g�}&m��?ċ�"����Om#��������� ��{�ON��"S�X��Ne��ysQ���@Fn��Vg���dX�~nj�]J�<�K]:��FW��b�������62�=��5f����JKw��bf�X�55��~J �%^����:�-�QIE��P��v�nZum� z � ~ə ���� ���ة����;�f��\v���g�8�1��f24;�V���ǔ�)����9���1\��c��v�/'Ƞ�w�������$�4�R-��t���� e�6�/�ġ �̕Ecy�J���u�B���<�W�ַ~�w[B1L۲�-JS΂�{���΃������A��20�c#��@ 0!1@AP"#2Q`$3V�%45a6�FRUq��� ����^7ׅ,$n�������+��F�`��2X'��0vM��p�L=������5��8������u�p~���.�`r�����\���O��,ư�0oS ��_�M�����l���4�kv\JSd���x���SW�<��Ae�IX����������$I���w�:S���y���›R��9�Q[���,�5�;�@]�%���u�@ *ro�lbI �� ��+���%m:�͇ZV�����u�̉����θau<�fc�.����{�4Ա� �Q����*�Sm��8\ujqs]{kN���)qO�y�_*dJ�b�7���yQqI&9�ԌK!�M}�R�;������S�T���1���i[U�ɵz�]��U)V�S6���3$K{�ߊ<�(� E]Զ[ǼENg�����'�\?#)Dkf��J���o��v���'�%ƞ�&K�u�!��b�35LX�Ϸ��63$K�a�;�9>,R��W��3�3� d�JeTYE.Mϧ��-�o�j3+y��y^�c�������VO�9NV\nd�1 ��!͕_)a�v;����թ�M�lWR1��)El��P;��yوÏ�u 3�k�5Pr6<�⒲l�!˞*��u־�n�!�l:����UNW ��%��Chx8vL'��X�@��*��)���̮��ˍ��� ���D-M�+J�U�kvK����+�x8��cY������?�Ԡ��~3mo��|�u@[XeY�C�\Kp�x8�oC�C�&����N�~3-H���� ��MX�s�u<`���~"WL��$8ξ��3���a�)|:@�m�\���^�`�@ҷ)�5p+��6���p�%i)P M���ngc�����#0Aruz���RL+xSS?���ʮ}()#�t��mˇ!��0}}y����<�e� �-ή�Ԩ��X������ MF���ԙ~l L.3���}�V뽺�v�����멬��Nl�)�2����^�Iq��a��M��qG��T�����c3#������3U�Ǎ���}��לS�|qa��ڃ�+���-��2�f����/��bz��ڐ�� �ݼ[2�ç����k�X�2�* �Z�d���J�G����M*9W���s{��w���T��x��y,�in�O�v��]���n����P�$�JB@=4�OTI�n��e�22a\����q�d���%�$��(���:���: /*�K[PR�fr\nڙdN���F�n�$�4�[�� U�zƶ����� �mʋ���,�ao�u 3�z� �x��Kn����\[��VFmbE;�_U��&V�Gg�]L�۪&#n%�$ɯ�dG���D�TI=�%+AB�Ru#��b4�1�»x�cs�YzڙJG��f��Il��d�eF'T� iA��T���uC�$����Y��H?����[!G`}���ͪ� �纤Hv\������j�Ex�K���!���OiƸ�Yj�+u-<���'q����uN�*�r\��+�]���<�wOZ.fp�ێ��,-*)V?j-kÊ#�`�r��dV����(�ݽBk�����G�ƛk�QmUڗe��Z���f}|����8�8��a���i��3'J�����~G_�^���d�8w������ R�`(�~�.��u���l�s+g�bv���W���lGc}��u���afE~1�Ue������Z�0�8�=e�� f@/�jqEKQQ�J��oN��J���W5~M>$6�Lt�;$ʳ{���^��6�{����v6���ķܰg�V�cnn �~z�x�«�,2�u�?cE+Ș�H؎�%�Za�)���X>uW�Tz�Nyo����s���FQƤ��$��*�&�LLXL)�1�" L��eO��ɟ�9=���:t��Z���c��Ž���Y?�ӭV�wv�~,Y��r�ۗ�|�y��GaF�����C�����.�+� ���v1���fήJ�����]�S��T��B��n5sW}y�$��~z�'�c ��8 ��� ,! �p��VN�S��N�N�q��y8z˱�A��4��*��'������2n<�s���^ǧ˭P�Jޮɏ�U�G�L�J�*#��<�V��t7�8����TĜ>��i}K%,���)[��z�21z ?�N�i�n1?T�I�R#��m-�����������������1����lA�`��fT5+��ܐ�c�q՝��ʐ��,���3�f2U�եmab��#ŠdQ�y>\��)�SLY����w#��.���ʑ�f��� ,"+�w�~�N�'�c�O�3F�������N<���)j��&��,-� �љ���֊�_�zS���TǦ����w�>��?�������n��U仆�V���e�����0���$�C�d���rP �m�׈e�Xm�Vu� �L��.�bֹ��� �[Դaզ���*��\y�8�Է:�Ez\�0�Kq�C b��̘��cө���Q��=0Y��s�N��S.���3.���O�o:���#���v7�[#߫ ��5�܎�L���Er4���9n��COWlG�^��0k�%<���ZB���aB_���������'=��{i�v�l�$�uC���mƎҝ{�c㱼�y]���W�i ��ߧc��m�H� m�"�"�����;Y�ߝ�Z�Ǔ�����:S#��|}�y�,/k�Ld� TA�(�AI$+I3��;Y*���Z��}|��ӧO��d�v��..#:n��f>�>���ȶI�TX��� 8��y����"d�R�|�)0���=���n4��6ⲑ�+��r<�O�܂~zh�z����7ܓ�HH�Ga롏���nCo�>������a ���~]���R���̲c?�6(�q�;5%� |�uj�~z8R=X��I�V=�|{v�Gj\gc��q����z�؋%M�ߍ����1y��#��@f^���^�>N�����#x#۹��6�Y~�?�dfPO��{��P�4��V��u1E1J �*|���%���JN��`eWu�zk M6���q t[�� ��g�G���v��WIG��u_ft����5�j�"�Y�:T��ɐ���*�;� e5���4����q$C��2d�}���� _S�L#m�Yp��O�.�C�;��c����Hi#֩%+) �Ӎ��ƲV���SYź��g |���tj��3�8���r|���V��1#;.SQ�A[���S������#���`n�+���$��$I �P\[�@�s��(�ED�z���P��])8�G#��0B��[ى��X�II�q<��9�~[Z멜�Z�⊔IWU&A>�P~�#��dp<�?����7���c��'~���5 ��+$���lx@�M�dm��n<=e�dyX��?{�|Aef ,|n3�<~z�ƃ�uۧ�����P��Y,�ӥQ�*g�#먙R�\���;T��i,��[9Qi歉����c>]9�� ��"�c��P�� �Md?٥��If�ت�u��k��/����F��9�c*9��Ǎ:�ØF���z�n*�@|I�ށ9����N3{'��[�'ͬ�Ҳ4��#}��!�V� Fu��,�,mTIk���v C�7v���B�6k�T9��1�*l� '~��ƞF��lU��'�M ����][ΩũJ_�{�i�I�n��$���L�� j��O�dx�����kza۪��#�E��Cl����x˘�o�����V���ɞ�ljr��)�/,�߬h�L��#��^��L�ф�,íMƁe�̩�NB�L�����iL����q�}��(��q��6IçJ$�W�E$��:������=#����(�K�B����zђ <��K(�N�۫K�w��^O{!����)�H���>x�������lx�?>Պ�+�>�W���,Ly!_�D���Ō�l���Q�!�[ �S����J��1��Ɛ�Y}��b,+�Lo�x�ɓ)����=�y�oh�@�꥟/��I��ѭ=��P�y9��� �ۍYӘ�e+�p�Jnϱ?V\SO%�(�t� ���=?MR�[Ș�����d�/ ��n�l��B�7j� ��!�;ӥ�/�[-���A�>�dN�sLj ��,ɪv��=1c�.SQ�O3�U���ƀ�ܽ�E����������̻��9G�ϷD�7(�}��Ävӌ\�y�_0[w ���<΍>����a_��[0+�L��F.�޺��f�>oN�T����q;���y\��bՃ��y�jH�<|q-eɏ�_?_9+P���Hp$�����[ux�K w�Mw��N�ی'$Y2�=��q���KB��P��~������Yul:�[<����F1�2�O���5=d����]Y�sw:���Ϯ���E��j,_Q��X��z`H1,#II ��d�wr��P˂@�ZJV����y$�\y�{}��^~���[:N����ߌ�U�������O��d�����ؾe��${p>G��3c���Ė�lʌ�� ת��[��`ϱ�-W����dg�I��ig2��� ��}s ��ؤ(%#sS@���~���3�X�nRG�~\jc3�v��ӍL��M[JB�T��s3}��j�Nʖ��W����;7��ç?=X�F=-�=����q�ߚ���#���='�c��7���ڑW�I(O+=:uxq�������������e2�zi+�kuG�R��������0�&e�n���iT^J����~\jy���p'dtG��s����O��3����9* �b#Ɋ�� p������[Bws�T�>d4�ۧs���nv�n���U���_�~,�v����ƜJ1��s�� �QIz��)�(lv8M���U=�;����56��G���s#�K���MP�=��LvyGd��}�VwWBF�'�à �?MH�U�g2�� ����!�p�7Q��j��ڴ����=��j�u��� Jn�A s���uM������e��Ɔ�Ҕ�!)'��8Ϣ�ٔ��ޝ(��Vp���צ֖d=�IC�J�Ǡ{q������kԭ�߸���i��@K����u�|�p=..�*+����x�����z[Aqġ#s2a�Ɗ���RR�)*HRsi�~�a &f��M��P����-K�L@��Z��Xy�'x�{}��Zm+���:�)�) IJ�-i�u���� ���ܒH��'�L(7�y�GӜq���� j��� 6ߌg1�g�o���,kر���tY�?W,���p���e���f�OQS��!K�۟cҒA�|ս�j�>��=⬒��˧L[�� �߿2JaB~R��u�:��Q�] �0H~���]�7��Ƽ�I���(}��cq '�ήET���q�?f�ab���ӥvr� �)o��-Q��_'����ᴎo��K������;��V���o��%���~OK ����*��b�f:���-ťIR��`B�5!RB@���ï�� �u �̯e\�_U�_������� g�ES��3�������QT��a����x����U<~�c?�*�#]�MW,[8O�a�x��]�1bC|踤�P��lw5V%�)�{t�<��d��5���0i�XSU��m:��Z�┵�i�"��1�^B�-��P�hJ��&)O��*�D��c�W��vM��)����}���P��ܗ-q����\mmζZ-l@�}��a��E�6��F�@��&Sg@���ݚ�M����� ȹ 4����#p�\H����dYDo�H���"��\��..R�B�H�z_�/5˘����6��KhJR��P�mƶi�m���3�,#c�co��q�a)*Pt����R�m�k�7x�D�E�\Y�閣_X�<���~�)���c[[�BP����6�Yq���S��0����%_����;��Àv�~�| VS؇ ��'O0��F0��\���U�-�d@�����7�SJ*z��3n��y��P����O���������m�~�P�3|Y��ʉr#�C�<�G~�.,! ���bqx���h~0=��!ǫ�jy����l�O,�[B��~��|9��ٱ����Xly�#�i�B��g%�S��������tˋ���e���ې��\[d�t)��.+u�|1 ������#�~Oj����hS�%��i.�~X���I�H�m��0n���c�1uE�q��cF�RF�o���7� �O�ꮧ� ���ۛ{��ʛi5�rw?׌#Qn�TW��~?y$��m\�\o����%W� ?=>S�N@�� �Ʈ���R����N�)�r"C�:��:����� �����#��qb��Y�. �6[��2K����2u�Ǧ�HYR��Q�MV��� �G�$��Q+.>�����nNH��q�^��� ����q��mM��V��D�+�-�#*�U�̒ ���p욳��u:�������IB���m���PV@O���r[b= �� ��1U�E��_Nm�yKbN�O���U�}�the�`�|6֮P>�\2�P�V���I�D�i�P�O;�9�r�mAHG�W�S]��J*�_�G��+kP�2����Ka�Z���H�'K�x�W�MZ%�O�YD�Rc+o��?�q��Ghm��d�S�oh�\�D�|:W������UA�Qc yT�q������~^�H��/��#p�CZ���T�I�1�ӏT����4��"�ČZ�����}��`w�#�*,ʹ�� ��0�i��課�Om�*�da��^gJ݅{���l�e9uF#T�ֲ��̲�ٞC"�q���ߍ ոޑ�o#�XZTp����@ o�8��(jd��xw�]�,f���`~�|,s��^����f�1���t��|��m�򸄭/ctr��5s��7�9Q�4�H1꠲BB@l9@���C�����+�wp�xu�£Yc�9��?`@#�o�mH�s2��)�=��2�.�l����jg�9$�Y�S�%*L������R�Y������7Z���,*=�䷘$�������arm�o�ϰ���UW.|�r�uf����IGw�t����Zwo��~5 ��YյhO+=8fF�)�W�7�L9lM�̘·Y���֘YLf�큹�pRF���99.A �"wz��=E\Z���'a� 2��Ǚ�#;�'}�G���*��l��^"q��+2FQ� hj��kŦ��${���ޮ-�T�٭cf�|�3#~�RJ����t��$b�(R��(����r���dx� >U b�&9,>���%E\� Ά�e�$��'�q't��*�א���ެ�b��-|d���SB�O�O��$�R+�H�)�܎�K��1m`;�J�2�Y~9��O�g8=vqD`K[�F)k�[���1m޼c��n���]s�k�z$@��)!I �x՝"v��9=�ZA=`Ɠi �:�E��)`7��vI��}d�YI�_ �o�:ob���o ���3Q��&D&�2=�� �Ά��;>�h����y.*ⅥS������Ӭ�+q&����j|UƧ����}���J0��WW< ۋS�)jQR�j���Ư��rN)�Gű�4Ѷ(�S)Ǣ�8��i��W52���No˓� ۍ%�5brOn�L�;�n��\G����=�^U�dI���8$�&���h��'���+�(������cȁ߫k�l��S^���cƗjԌE�ꭔ��gF���Ȓ��@���}O���*;e�v�WV���YJ\�]X'5��ղ�k�F��b 6R�o՜m��i N�i����>J����?��lPm�U��}>_Z&�KK��q�r��I�D�Չ~�q�3fL�:S�e>���E���-G���{L�6p�e,8��������QI��h��a�Xa��U�A'���ʂ���s�+טIjP�-��y�8ۈZ?J$��W�P� ��R�s�]��|�l(�ԓ��sƊi��o(��S0��Y� 8�T97.�����WiL��c�~�dxc�E|�2!�X�K�Ƙਫ਼�$((�6�~|d9u+�qd�^3�89��Y�6L�.I�����?���iI�q���9�)O/뚅����O���X��X�V��ZF[�یgQ�L��K1���RҖr@v�#��X�l��F���Нy�S�8�7�kF!A��sM���^rkp�jP�DyS$N���q��nxҍ!U�f�!eh�i�2�m���`�Y�I�9r�6� �TF���C}/�y�^���Η���5d�'��9A-��J��>{�_l+�`��A���[�'��յ�ϛ#w:݅�%��X�}�&�PSt�Q�"�-��\縵�/����$Ɨh�Xb�*�y��BS����;W�ջ_mc�����vt?2}1�;qS�d�d~u:2k5�2�R�~�z+|HE!)�Ǟl��7`��0�<�,�2*���Hl-��x�^����'_TV�gZA�'j� ^�2Ϊ��N7t�����?w�� �x1��f��Iz�C-Ȗ��K�^q�;���-W�DvT�7��8�Z�������� hK�(P:��Q- �8�n�Z���܃e貾�<�1�YT<�,�����"�6{/ �?�͟��|1�:�#g��W�>$����d��J��d�B��=��jf[��%rE^��il:��B���x���Sּ�1հ��,�=��*�7 fcG��#q� �eh?��2�7�����,�!7x��6�n�LC�4x��},Geǝ�tC.��vS �F�43��zz\��;QYC,6����~;RYS/6���|2���5���v��T��i����������mlv��������&� �nRh^ejR�LG�f���? �ۉҬܦƩ��|��Ȱ����>3����!v��i�ʯ�>�v��オ�X3e���_1z�Kȗ\<������!�8���V��]��?b�k41�Re��T�q��mz��TiOʦ�Z��Xq���L������q"+���2ۨ��8}�&N7XU7Ap�d�X��~�׿��&4e�o�F��� �H����O���č�c�� 懴�6���͉��+)��v;j��ݷ�� �UV�� i��� j���Y9GdÒJ1��詞�����V?h��l����l�cGs�ځ�������y�Ac�����\V3�? �� ܙg�>qH�S,�E�W�[�㺨�uch�⍸�O�}���a��>�q�6�n6����N6�q������N ! 1AQaq�0@����"2BRb�#Pr���3C`��Scst���$4D���%Td�� ?���N����a��3��m���C���w��������xA�m�q�m���m������$����4n淿t'��C"w��zU=D�\R+w�p+Y�T�&�պ@��ƃ��3ޯ?�Aﶂ��aŘ���@-�����Q�=���9D��ռ�ѻ@��M�V��P��܅�G5�f�Y<�u=,EC)�<�Fy'�"�&�չ�X~f��l�KԆV��?�� �W�N����=(� �;���{�r����ٌ�Y���h{�١������jW����P���Tc�����X�K�r��}���w�R��%��?���E��m�� �Y�q|����\lEE4���r���}�lsI�Y������f�$�=�d�yO����p�����yBj8jU�o�/�S��?�U��*������ˍ�0������u�q�m [�?f����a�� )Q�>����6#������� ?����0UQ����,IX���(6ڵ[�DI�MNލ�c&���υ�j\��X�R|,4��� j������T�hA�e��^���d���b<����n�� �즇�=!���3�^�`j�h�ȓr��jẕ�c�,ٞX����-����a�ﶔ���#�$��]w�O��Ӫ�1y%��L�Y<�wg#�ǝ�̗`�x�xa�t�w��»1���o7o5��>�m뭛C���Uƃߜ}�C���y1Xνm�F8�jI���]����H���ۺиE@I�i;r�8ӭ����V�F�Շ| ��&?�3|x�B�MuS�Ge�=Ӕ�#BE5G�����Y!z��_e��q�р/W>|-�Ci߇�t�1ޯќd�R3�u��g�=0 5��[?�#͏��q�cf���H��{ ?u�=?�?ǯ���}Z��z���hmΔ�BFTW�����<�q�(v� ��!��z���iW]*�J�V�z��gX֧A�q�&��/w���u�gYӘa���; �i=����g:��?2�dž6�ى�k�4�>�Pxs����}������G�9��3 ���)gG�R<>r h�$��'nc�h�P��Bj��J�ҧH� -��N1���N��?��~��}-q!=��_2hc�M��l�vY%UE�@|�v����M2�.Y[|y�"Eï��K�ZF,�ɯ?,q�?v�M 80jx�"�;�9vk�����+ ֧�� �ȺU��?�%�vcV��mA�6��Qg^M����A}�3�nl� QRN�l8�kkn�'�����(��M�7m9و�q���%ޟ���*h$Zk"��$�9��: �?U8�Sl��,,|ɒ��xH(ѷ����Gn�/Q�4�P��G�%��Ա8�N��!� �&�7�;���eKM7�4��9R/%����l�c>�x;������>��C�:�����t��h?aKX�bhe�ᜋ^�$�Iհ �hr7%F$�E��Fd���t��5���+�(M6�t����Ü�UU|zW�=a�Ts�Tg������dqP�Q����b'�m���1{|Y����X�N��b �P~��F^F:����k6�"�j!�� �I�r�`��1&�-$�Bevk:y���#yw��I0��x��=D�4��tU���P�ZH��ڠ底taP��6����b>�xa����Q�#� WeF��ŮNj�p�J* mQ�N����*I�-*�ȩ�F�g�3 �5��V�ʊ�ɮ�a��5F���O@{���NX��?����H�]3��1�Ri_u��������ѕ�� ����0��� F��~��:60�p�͈�S��qX#a�5>���`�o&+�<2�D����: �������ڝ�$�nP���*)�N�|y�Ej�F�5ټ�e���ihy�Z �>���k�bH�a�v��h�-#���!�Po=@k̆IEN��@��}Ll?j�O������߭�ʞ���Q|A07x���wt!xf���I2?Z��<ץ�T���cU�j��]��陎Ltl �}5�ϓ��$�,��O�mˊ�;�@O��jE��j(�ا,��LX���LO���Ц�90�O �.����a��nA���7������j4 ��W��_ٓ���zW�jcB������y՗+EM�)d���N�g6�y1_x��p�$Lv:��9�"z��p���ʙ$��^��JԼ*�ϭ����o���=x�Lj�6�J��u82�A�H�3$�ٕ@�=Vv�]�'�qEz�;I˼��)��=��ɯ���x �/�W(V���p�����$ �m�������u�����񶤑Oqˎ�T����r��㠚x�sr�GC��byp�G��1ߠ�w e�8�$⿄����/�M{*}��W�]˷.�CK\�ުx���/$�WPw���r� |i���&�}�{�X� �>��$-��l���?-z���g����lΆ���(F���h�vS*���b���߲ڡn,|)mrH[���a�3�ר�[1��3o_�U�3�TC�$��(�=�)0�kgP���� ��u�^=��4 �WYCҸ:��vQ�ר�X�à��tk�m,�t*��^�,�}D*� �"(�I��9R����>`�`��[~Q]�#af��i6l��8���6�:,s�s�N6�j"�A4���IuQ��6E,�GnH��zS�HO�uk�5$�I�4��ؤ�Q9�@��C����wp�BGv[]�u�Ov���0I4���\��y�����Q�Ѹ��~>Z��8�T��a��q�ޣ;z��a���/��S��I:�ܫ_�|������>=Z����8:�S��U�I�J��"IY���8%b8���H��:�QO�6�;7�I�S��J��ҌAά3��>c���E+&jf$eC+�z�;��V����� �r���ʺ������my�e���aQ�f&��6�ND��.:��NT�vm�<- u���ǝ\MvZY�N�NT��-A�>jr!S��n�O 1�3�Ns�%�3D@���`������ܟ 1�^c<���� �a�ɽ�̲�Xë#�w�|y�cW�=�9I*H8�p�^(4���՗�k��arOcW�tO�\�ƍR��8����'�K���I�Q�����?5�>[�}��yU�ײ -h��=��% q�ThG�2�)���"ו3]�!kB��*p�FDl�A���,�eEi�H�f�Ps�����5�H:�Փ~�H�0Dت�D�I����h�F3�������c��2���E��9�H��5�zԑ�ʚ�i�X�=:m�xg�hd(�v����׊�9iS��O��d@0ڽ���:�p�5�h-��t�&���X�q�ӕ,��ie�|���7A�2���O%P��E��htj��Y1��w�Ѓ!����  ���� ࢽ��My�7�\�a�@�ţ�J �4�Ȼ�F�@o�̒?4�wx��)��]�P��~�����u�����5�����7X ��9��^ܩ�U;Iꭆ 5 �������eK2�7(�{|��Y׎ �V��\"���Z�1� Z�����}��(�Ǝ"�1S���_�vE30>���p;� ΝD��%x�W�?W?v����o�^V�i�d��r[��/&>�~`�9Wh��y�;���R��� ;;ɮT��?����r$�g1�K����A��C��c��K��l:�'��3 c�ﳯ*"t8�~l��)���m��+U,z��`(�>yJ�?����h>��]��v��ЍG*�{`��;y]��I�T� ;c��NU�fo¾h���/$���|NS���1�S�"�H��V���T���4��uhǜ�]�v;���5�͠x��'C\�SBpl���h}�N����� A�Bx���%��ޭ�l��/����T��w�ʽ]D�=����K���ž�r㻠l4�S�O?=�k �M:� ��c�C�a�#ha���)�ѐxc�s���gP�iG��{+���x���Q���I= �� z��ԫ+ �8"�k�ñ�j=|����c ��y��CF��/��*9ж�h{ �?4�o� ��k�m�Q�N�x��;�Y��4膚�a�w?�6�>e]�����Q�r�:����g�,i"�����ԩA�*M�<�G��b�if��l^M��5� �Ҩ�{����6J��ZJ�����P�*�����Y���ݛu�_4�9�I8�7���������,^ToR���m4�H��?�N�S�ѕw��/S��甍�@�9H�S�T��t�ƻ���ʒU��*{Xs�@����f�����֒Li�K{H�w^���������Ϥm�tq���s� ���ք��f:��o~s��g�r��ט� �S�ѱC�e]�x���a��) ���(b-$(�j>�7q�B?ӕ�F��hV25r[7 Y� }L�R��}����*sg+��x�r�2�U=�*'WS��ZDW]�WǞ�<��叓���{�$�9Ou4��y�90-�1�'*D`�c�^o?(�9��u���ݐ��'PI&� f�Jݮ�������:wS����jfP1F:X �H�9dԯ���˝[�_54 �}*;@�ܨ�� ð�yn�T���?�ןd�#���4rG�ͨ��H�1�|-#���Mr�S3��G�3�����)�.᧏3v�z֑��r����$G"�`j �1t��x0<Ɔ�Wh6�y�6��,œ�Ga��gA����y��b��)��h�D��ß�_�m��ü �gG;��e�v��ݝ�nQ� ��C����-�*��o���y�a��M��I�>�<���]obD��"�:���G�A��-\%LT�8���c�)��+y76���o�Q�#*{�(F�⽕�y����=���rW�\p���۩�c���A���^e6��K������ʐ�cVf5$�'->���ՉN"���F�"�UQ@�f��Gb~��#�&�M=��8�ט�JNu9��D��[̤�s�o�~������ G��9T�tW^g5y$b��Y'��س�Ǵ�=��U-2 #�MC�t(�i� �lj�@Q 5�̣i�*�O����s�x�K�f��}\��M{E�V�{�υ��Ƈ�����);�H����I��fe�Lȣr�2��>��W�I�Ȃ6������i��k�� �5�YOxȺ����>��Y�f5'��|��H+��98pj�n�.O�y�������jY��~��i�w'������l�;�s�2��Y��:'lg�ꥴ)o#'Sa�a�K��Z� �m��}�`169�n���"���x��I ��*+� }F<��cГ���F�P�������ֹ*�PqX�x۩��,� ��N�� �4<-����%����:��7����W���u�`����� $�?�I��&����o��o��`v�>��P��"��l���4��5'�Z�gE���8���?��[�X�7(��.Q�-��*���ތL@̲����v��.5���[��=�t\+�CNܛ��,g�SQnH����}*F�G16���&:�t��4ُ"A��̣��$�b �|����#rs��a�����T�� ]�<�j��BS�('$�ɻ� �wP;�/�n��?�ݜ��x�F��yUn�~mL*-�������Xf�wd^�a�}��f�,=t�׵i�.2/wpN�Ep8�OР���•��R�FJ� 55TZ��T �ɭ�<��]��/�0�r�@�f��V��V����Nz�G��^���7hZi����k��3�,kN�e|�vg�1{9]_i��X5y7� 8e]�U����'�-2,���e"����]ot�I��Y_��n�(JҼ��1�O ]bXc���Nu�No��pS���Q_���_�?i�~�x h5d'�(qw52] ��'ޤ�q��o1�R!���`ywy�A4u���h<קy���\[~�4�\ X�Wt/� 6�����n�F�a8��f���z �3$�t(���q��q�x��^�XWeN'p<-v�!�{�(>ӽDP7��ո0�y)�e$ٕv�Ih'Q�EA�m*�H��RI��=:��� ���4牢) �%_iN�ݧ�l]� �Nt���G��H�L��� ɱ�g<���1V�,�J~�ٹ�"K��Q�� 9�HS�9�?@��k����r�;we݁�]I�!{ �@�G�[�"��`���J:�n]�{�cA�E����V��ʆ���#��U9�6����j�#Y�m\��q�e4h�B�7��C�������d<�?J����1g:ٳ���=Y���D�p�ц� ׈ǔ��1�]26؜oS�'��9�V�FVu�P�h�9�xc�oq�X��p�o�5��Ա5$�9W�V(�[Ak�aY錎qf;�'�[�|���b�6�Ck��)��#a#a˙��8���=äh�4��2��C��4tm^ �n'c���]GQ$[Wҿ��i���vN�{Fu ��1�gx��1┷���N�m��{j-,��x�� Ūm�ЧS�[�s���Gna���䑴�� x�p 8<������97�Q���ϴ�v�aϚG��Rt�Һ׈�f^\r��WH�JU�7Z���y)�vg=����n��4�_)y��D'y�6�]�c�5̪�\� �PF�k����&�c;��cq�$~T�7j ���nç]�<�g ":�to�t}�159�<�/�8������m�b�K#g'I'.W�����6��I/��>v��\�MN��g���m�A�yQL�4u�Lj�j9��#44�t��l^�}L����n��R��!��t��±]��r��h6ٍ>�yҏ�N��fU�� ���� Fm@�8}�/u��jb9������he:A�y�ծw��GpΧh�5����l}�3p468��)U��d��c����;Us/�֔�YX�1�O2��uq�s��`hwg�r~�{ R��mhN��؎*q 42�*th��>�#���E����#��Hv�O����q�}�����6�e��\�,Wk�#���X��b>��p}�դ��3���T5��†��6��[��@�P�y*n��|'f�֧>�lư΂�̺����SU�'*�q�p�_S�����M�� '��c�6�����m�� ySʨ;M��r���Ƌ�m�Kxo,���Gm�P��A�G�:��i��w�9�}M(�^�V��$ǒ�ѽ�9���|���� �a����J�SQ�a���r�B;����}���ٻ֢�2�%U���c�#�g���N�a�ݕ�'�v�[�OY'��3L�3�;,p�]@�S��{ls��X�'���c�jw�k'a�.��}�}&�� �dP�*�bK=ɍ!����;3n�gΊU�ߴmt�'*{,=SzfD� A��ko~�G�aoq�_mi}#�m�������P�Xhύ����mxǍ�΂���巿zf��Q���c���|kc�����?���W��Y�$���_Lv����l߶��c���`?����l�j�ݲˏ!V��6����U�Ђ(A���4y)H���p�Z_�x��>���e��R��$�/�`^'3qˏ�-&Q�=?��CFVR �D�fV�9��{�8g�������n�h�(P"��6�[�D���< E�����~0<@�`�G�6����Hг�cc�� �c�K.5��D��d�B���`?�XQ��2��ٿyqo&+�1^� DW�0�ꊩ���G�#��Q�nL3��c���������/��x ��1�1[y�x�პCW��C�c�UĨ80�m�e�4.{�m��u���I=��f�����0QRls9���f���������9���~f�����Ǩ��a�"@�8���ȁ�Q����#c�ic������G��$���G���r/$W�(��W���V�"��m�7�[m�A�m����bo��D� j����۳� l���^�k�h׽����� ��#� iXn�v��eT�k�a�^Y�4�BN��ĕ��0 !01@Q"2AaPq3BR������?���@4�Q�����T3,���㺠�W�[=JK�Ϟ���2�r^7��vc�:�9 �E�ߴ�w�S#d���Ix��u��:��Hp��9E!�� V 2;73|F��9Y���*ʬ�F��D����u&���y؟��^EA��A��(ɩ���^��GV:ݜDy�`��Jr29ܾ�㝉��[���E;Fzx��YG��U�e�Y�C���� ����v-tx����I�sם�Ę�q��Eb�+P\ :>�i�C'�;�����k|z�رn�y]�#ǿb��Q��������w�����(�r|ӹs��[�D��2v-%��@;�8<a���[\o[ϧw��I!��*0�krs)�[�J9^��ʜ��p1)� "��/_>��o��<1����A�E�y^�C��`�x1'ܣn�p��s`l���fQ��):�l����b>�Me�jH^?�kl3(�z:���1ŠK&?Q�~�{�ٺ�h�y���/�[��V�|6��}�KbX����mn[-��7�5q�94�������dm���c^���h� X��5��<�eޘ>G���-�}�دB�ޟ� ��|�rt�M��V+�]�c?�-#ڛ��^ǂ}���Lkr���O��u�>�-D�ry� D?:ޞ�U��ǜ�7�V��?瓮�"�#���r��չģVR;�n���/_� ؉v�ݶe5d�b9��/O��009�G���5n�W����JpA�*�r9�>�1��.[t���s�F���nQ� V 77R�]�ɫ8����_0<՜�IF�u(v��4��F�k�3��E)��N:��yڮe��P�`�1}�$WS��J�SQ�N�j�ٺ��޵�#l���ј(�5=��5�lǏmoW�v-�1����v,W�mn��߀$x�<����v�j(����c]��@#��1������Ǔ���o'��u+����;G�#�޸��v-lη��/(`i⣍Pm^���ԯ̾9Z��F��������n��1��� ��]�[��)�'������:�֪�W��FC����� �B9،!?���]��V��A�Վ�M��b�w��G F>_DȬ0¤�#�QR�[V��kz���m�w�"��9ZG�7'[��=�Q����j8R?�zf�\a�=��O�U����*oB�A�|G���2�54 �p��.w7� �� ��&������ξxGHp� B%��$g�����t�Џ򤵍z���HN�u�Я�-�'4��0��;_��3 !01"@AQa2Pq#3BR������?��ʩca��en��^��8���<�u#��m*08r��y�N"�<�Ѳ0��@\�p��� �����Kv�D��J8�Fҽ� �f�Y��-m�ybX�NP����}�!*8t(�OqѢ��Q�wW�K��ZD��Δ^e��!� ��B�K��p~�����e*l}z#9ң�k���q#�Ft�o��S�R����-�w�!�S���Ӥß|M�l޶V��!eˈ�8Y���c�ЮM2��tk���� ������J�fS����Ö*i/2�����n]�k�\���|4yX�8��U�P.���Ы[���l��@"�t�<������5�lF���vU�����W��W��;�b�cД^6[#7@vU�xgZv��F�6��Q,K�v��� �+Ъ��n��Ǣ��Ft���8��0��c�@�!�Zq s�v�t�;#](B��-�nῃ~���3g������5�J�%���O������n�kB�ĺ�.r��+���#�N$?�q�/�s�6��p��a����a��J/��M�8��6�ܰ"�*������ɗud"\w���aT(����[��F��U՛����RT�b���n�*��6���O��SJ�.�ij<�v�MT��R\c��5l�sZB>F��<7�;EA��{��E���Ö��1U/�#��d1�a�n.1ě����0�ʾR�h��|�R��Ao�3�m3 ��%�� ���28Q� ��y��φ���H�To�7�lW>����#i`�q���c����a��� �m,B�-j����݋�'mR1Ήt�>��V��p���s�0IbI�C.���1R�ea�����]H�6����������4B>��o��](��$B���m�����a�!=��?�B� K�Ǿ+�Ծ"�n���K��*��+��[T#�{E�J�S����Q�����s�5�:�U�\wĐ�f�3����܆&�)����I���Ԇw��E T�lrTf6Q|R�h:��[K�� �z��c֧�G�C��%\��_�a�84��HcO�bi��ؖV��7H �)*ģK~Xhչ0��4?�0��� �E<���}3���#���u�?�� ��|g�S�6ꊤ�|�I#Hڛ� �ա��w�X��9��7���Ŀ%�SL��y6č��|�F�a 8���b��$�sק�h���b9RAu7�˨p�Č�_\*w��묦��F ����4D~�f����|(�"m���NK��i�S�>�$d7SlA��/�²����SL��|6N�}���S�˯���g��]6��; �#�.��<���q'Q�1|KQ$�����񛩶"�$r�b:���N8�w@��8$�� �AjfG|~�9F ���Y��ʺ��Bwؒ������M:I岎�G��`s�YV5����6��A �b:�W���G�q%l�����F��H���7�������Fsv7��k�� 403WebShell
403Webshell
Server IP : 172.67.215.126  /  Your IP : 172.69.130.121
Web Server : Apache/2.4.52 (Ubuntu)
System : Linux ip-172-31-19-221 6.8.0-1029-aws #31~22.04.1-Ubuntu SMP Thu Apr 24 21:16:18 UTC 2025 x86_64
User : www-data ( 33)
PHP Version : 8.1.28
Disable Function : NONE
MySQL : OFF  |  cURL : ON  |  WGET : ON  |  Perl : ON  |  Python : OFF  |  Sudo : ON  |  Pkexec : ON
Directory :  /efsdata/scitechnol.com/httpdocs/submission/uploads/

Upload File :
current_dir [ Writeable ] document_root [ Writeable ]

 

Command :


[ Back ]     

Current File : /efsdata/scitechnol.com/httpdocs/submission/uploads/1442-2-Manuscript-2013-12-17.doc
��ࡱ�>��	|~����{��������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������	��&@bjbj�W�W	.h�=�=8%���������@@@@@����TTT8�d�<TQVt,(T"vvvQQQ�U�U�U�U�U�U�U$�W�wZr�U@	QQ		�U@@vv�V
"
"
"	�@v@v�U
"	�U
"
"�
I�"Mv�����a������������J&�U!V0QV�Jf�Z���ZL"M"M��Z@�SQo�
";��*QQQ�U�U �QQQQV				���������������������������������������������������������������������ZQQQQQQQQQ� :	Title: Original Research: Pupillary Constriction Velocity and Latency to Predict Excessive Daytime Sleepiness

Authors and Institution:
Vyas Umesh MD1, Woodson B Tucker MD2

1. Chair of Department of Psychiatry, Regional Medical Director of Behavioral Health, Regional Medical Director of Sleep Disorders Center, Mayo Clinic Health System, Mankato, MN, USA
Address: 101 Callaway Court, Mankato, MN, 56001-6299, USA
Email:  HYPERLINK "mailto:vyas.umesh@mayo.edu" vyas.umesh@mayo.edu
Phone Number: 507 779 5176
Fax Number: 507 385 6426

2. Professor and Chief Division of Sleep Medicine, Department of Otolaryngology and Human Communication, Medical College of Wisconsin, WI, USA

Conflict of interest: The authors declare that we have no conflict of interest.




























Key words:
Excessive daytime sleepiness (EDS); Pupillometry; Constriction velocity; Constriction latency
















Introduction:
Excessive daytime sleepiness (EDS) is common in adults, it is very common clinical complain in sleep clinic, it can be due to verity of reasons but most commonly due to sleep deprivation syndrome and Sleep Related Breathing Disorder, approximately 5% of adults complain of EDS [1, 2]. Sleepiness may present as increased propensity for sleep, decreased propensity for wake, or alterations in mood or neuro-cognitive function, pt may present this complaint as tiredness, and evaluation of this complaint requires an awareness of various meanings of tiredness. The consequences of EDS can range from discomfort in social situation to life threatening such as falling asleep while driving. A public health threat with economic costs in the billions, drowsy driving is related to at least 100,000 motor vehicle accidents and more than 1500 deaths per year in United States. [ HYPERLINK "http://www.sleepeducation.com" www.sleepeducation.com]

EDS is a condition that can significantly reduce quality of life, decrease productivity and interfere with relationships. If EDS persists is neither normal nor healthy. One of the primary causes of EDS among Americans is self-imposed sleep deprivation. By some estimates, people now sleep about 20 percent less than they did a century ago. EDS is also linked with a number of primary sleep disorders, also caused by variety of physical and mental illnesses as well as some medications.

According to the results of National Sleep Foundation (NSF�s) 2008 Sleep in America Poll:
36 percent of Americans drive drowsy or fall asleep while driving (one of the most serious risks associated with EDS)
29 percent of Americans fall asleep or become sleepy at work
20 percent of Americans have lost interest in sex because they are too sleepy
14 percent of Americans report having to miss family events, work functions and leisure activities in the past month due to sleepiness
Each of these consequences can have enormous impact on an individual�s health and happiness.

There are several self-rating scales available to rate severity of sleepiness e.g. Visual Analogue Scale (VAS) [3], Stanford Sleepiness Scale (SSS) [4], Epworth Sleepiness Scale (EPS) [5]. These depend on patient perception of sleepiness, motivation, and are subjective. The accepted objective clinical methods to assess sleepiness include the Multiple Sleep Latency Test (MSLT) and Maintenance of Wakefulness Test (MWT); however, these are time and resource consuming. These tests are not portable and often cumbersome for patients and researchers. MSLT and MWT are not perfect tests, but they are the best objective tests currently available for characterization of ability to fall asleep and ability to remain awake respectively. A need exists (Institute of Medicine of the National Academics, 2006, Sleep Disorders and Sleep Deprivation) for an easier and faster objective clinical measures of EDS.

The autonomic nervous system controls pupil size and prior pupillometry studies have demonstrated associations with papillary function affected by EDS [6]. We used a novel portable device to assess pupillometry and prospectively evaluated a sleep clinic cohort.

Rationale:
Sleepiness effects the Autonomic Nervous System [Figure 1]
Sleep increases Parasympathetic tone (non REM)
Sleep decreases Sympathetic tone
Pupillary Constriction velocity is a function of the balance between Sympathetic and Parasympathetic tone
Increased Sympathetic balance decreases constriction velocity
Increased Parasympathetic balance increases constriction velocity

Objective:
To evaluate portable pupillometry in measuring pupillary constriction velocity and latency (a metric of autonomic system sympathetic and parasympathetic balance) as an assessment of sleepiness in a sleep clinic population.

Inclusion/Exclusion criteria:
Patients and control subjects were recruited from a sleep disorders and a general otolaryngology clinic at the Medical College of Wisconsin (MCW), Milwaukee, WI, USA and included patients with and without obstructive sleep apnea (OSA).

We studied male and female patients of any ethnicity older than 18 years of age. Patients with a diagnosis of a primary autonomic neuropathy, who have undergone cataract surgery, have glaucoma, blindness in one or both eyes or recent history of head trauma (< 6 months) excluded. Patients who are pregnant or have reasonable grounds to believe they are pregnant also excluded. All of the above can alter pupillary measures or affect the autonomic nervous system.

Information about ForSiteTM Pupillometry [Figure 2]:
The ForSiteTM Pupillometer, NeurOptics, is a hand-held portable, single button operated device measures pupil size, speed of reaction, and rate of constriction and dilatation with autonomic changes. This instrument is suitable robust tool for measuring papillary changes. Pupillometry was originally proposed by Lowenstein et al in 1958, and has been used in a number of studies to evaluate somnolence in patients [11].

Pupil response to light are under control of sympathetic and parasympathetic nervous system (autonomic nervous system), mydriasis by sympathetic and miosis by parasympathetic system. This device is an FDA Class I exempt device currently available for assessing pupillary function in patients with head trauma. The device consists of a disposable bracket that rests on the subject�s forehead and cheek for stability. The subject focuses at a fixed distance (between 5-7 feet away) and does not blink for several seconds. The device emits a light causing the pupil to constrict. The device then measures the pupillary response at 40 frames per second. The device processes the data and reports on an LCD screen the maximum and minimum aperture, construction velocity, dilation velocity and latency of response. All measurements began with the right eye (R1) and subsequently alternated between eyes for a total of 6 measurements (e.g., R1, L1, R2, L2, R3, and L3). Complete pupillometric testing took approximately 5 minutes per patient.

Subjects are tested in a room with ambient light of 60-120 as determined by the device. The amount of light emitted from the device is approximately 125 microwatts with the irradiance of about 325 microwatts/cm2 at the pupil. The LED light sources are 5 mm in diameter and are placed approximately 51 mm from the design plane of the pupil at an incline of about 16 degrees from the optical axis of the device. The duration of light pulse is 800 milliseconds.

The velocities are calculated as a fit to the slope of the constriction and dilation phase of the pupil reflex. There is a nonlinear aspect to the fit of the constriction; however, this in reality is close to a linear fit most of the time. The fitting algorithms are applied to those segments of the pupillary light reflex which are demarked by the points of inflection which denote a change in direction. A sustained change (magnitude and direction) seen over at least 3 frames of data is required to validate an inflection point as being the onset of motion. Some articles in the literature report constriction velocity as the maximum speed observed in the constriction phase and likewise the latency reported is the time required to reach maximum velocity for initiation of the stimulus. The ForesiteTM device uses the first sustained and verifiable movement in the calculations.

The scientific premise behind pupillometry is that pupil size and stability are inversely related to the degree of subjective sleepiness, normal pupil size is determined by the interaction between the parasympathetic and sympathetic nervous systems input to the muscles of the iris, the sphincter and the dilator, respectively.

In a state of arousal there is increased sympathetic tone, resulting in mydriasis. Conversely in the state of drowsiness, there is predominance of parasympathetic tone, resulting in miosis [8].

Sleep-deprived individuals will demonstrate the inability to maintain their pupil size as evidenced by frequent papillary oscillations during the testing period. A well rested, alert subject is able to maintain a stable pupil size without oscillation in total darkness for 15 minutes [11]. To derive reliable results; pts need to be free of any medications that may affect the parasympathetic or sympathetic pathways. A study demonstrated a strong relationship between ongoing sleep deprivation in normal subjects and typical changes in frequency profiles of spontaneous papillary oscillations and the tendency toward instability of pupil size [12], with ongoing sleep deprivation, slow pupillary oscillations and Stanford Sleepiness Scale (SSS) scores significantly increased, where as pupil diameter decreased significantly. Currently, pupillometry is not a widely used clinical measurement of sleepiness, predominantly because the equipment is not readily available. Further research is necessary to determine the role of pupillometry in the assessment of daytime sleepiness in clinical practice.

One study reported that the median values of most pupillometric variables in our sleepiest patients (mean sleep latency less than 5 min) were significantly greater than those of well-rested normal volunteers. None of the variables was significantly different between mildly sleepy group of patents (latency >10 min) and the group of normal volunteers [6]. They further concluded that study suggests that there is a clear relationship between pupillometric variables and excessive daytime somnolence, as noted by Yoss [7, 8] and others [9, 10].

Design of study:
Prospective, controlled, cross-sectional study with correlation of objective and subjective measures of sleepiness

Methods:
Following Internal Review Board (IRB) approval and after obtaining informed consent from all controls and subjects, Pupillometry (The ForsiteTM, NeurOptics, Irvine, CA), was performed on 113 sleep clinic patients. Patient presented Constriction and dilation velocity and latencies, minimum and maximum aperture were obtained along with Epworth Sleepiness Score (ESS), 10 point Visual Analog Scale (VAS), BMI, gender, age and AHI. Three sets of measures were obtained and analyzed with ANOVA, t-test, Linear Regression and Pearson correlation coefficients (SAS, Cary, NC).

Mean Age 47 Years
Mean Epworth Sleepiness score = 11.5
Mean VAS score = 6.5

Results (Figure 3-8, Table 1):
Both constriction velocity and constriction latency correlated with VAS (n=88, r=0.28, p=0.007 and r= 0.31, p=0.004). Only constriction velocity correlated with AHI (n=78, r=-0.27, p=0.016). Multivariate linear regression which include VAS and age predicted constriction velocity (r=0.36, p=0.002) and latency (r=0.38, p=0.001). Using Pearson correlation, AHI and VAS combined were associated with constriction velocity (-0.273 (0.016), and 0.284 (0.007), respectively). Using a maximum constriction velocity threshold value (age adjusted) of 2.8, VAS > 6 was predicted with a sensitivity of 83% and specificity of 84%.

Conclusions:
Our study supports the concept of using portable ambulatory pupillometry to identify individuals at risk of abnormal sleepiness. Pupillometry measures of pupillary constriction velocity and constriction latency are both correlated to subjective sleepiness measured with a 10 point VAS. Pupillary constriction velocity was associated with sleepiness (VAS), AHI, and age. When corrected for age, pupillary constriction velocity successfully identified individuals with a VAS greater than 6. Pupillometry has the potential to be a rapid, widely available measure of subjective sleepiness.

References:
1. Lavie P. 1981. Sleep habits and sleep disturbances in industrial workers in Israel: main findings and some characteristics of workers complaining of excessive daytime sleepiness. Sleep; 4 (2):147-158

2. Bixler E. O., Kales A., Soldatos C. R., Kales J.D., Healey S. 1979, Prevalence of Sleep Disorders in the Los Angeles Metropolitan Area, Am J Psychiatry; 136 (10): 1257-1262

3. Moldofsky H. 1992, Evaluation of Daytime Sleepiness. Clinics in Chest Medicine; 13 (3): 417-425

4. Hoddes E., Zarcone V., Smythe H., Phillips R., Dement W.C. 1973, Quantification of Sleepiness: A New Approach. Psychophysiology; 10 (4): 431-436

5. Johns M. W. 1991, A New Method for measuring Daytime Sleepiness: The Epworth Sleepiness Scale. Sleep; 14: 540-545

6. McLaren J. W., Hauri P. J., Lin Siong-Chi, Harris C.D., 2002, Pupillometry in clinically sleepy patients. Sleep Medicine; 3: 347-352

7. Yoss R. E., Moyer N. Y., Ogle K. N., 1969; The Pupillogram and narcolepsy: A method to measure decreased levels of wakefulness. Neurology; 19 (10): 921-928

8. R. E. Yoss, N. Y. Moyer, R. W. Hollenhorst. Pupil size and spontaneous papillary waves associated with alertness, drowsiness, and sleep. Neurology 1970; 20: 545-554

9. Schmidt H. S. 1982; Pupillometric assessment of disorders of arousal. Sleep; 5: S157-S164

10. Newman J. Broughton R. 1991. Pupillometric Assessment of Excessive Daytime Sleepiness in Narcolepsy-Cataplexy. Sleep; 14 (2): 121-129

11. Lowenstein O, Feinberg R, Lowenfield I., 1963; Pupillary movements during acute and chronic fatigue: a new test for the objective evaluation of tiredness. Invest Ophthalmology; 2: 138-157

12. Wilhelm B, Wilhelm H, Ludtke H, Streicher P., Adler M., 1998, Pupillographic assessment of sleepiness in sleep deprived healthy subjects. Sleep; 21 (3): 258-265








PAGE  


PAGE  7




:=FHmno����������	
	9	_	d	e	p	�	�	�	�	�	�	�	�	�	�	�	�	�	




,
.
2
j
�
�����������������ʾ������ʶ������������«���ʇʇ��hVlhVlh8qwhy}bh;_=h�B?0J�jh�B?Ujh�B?Uh�B?hA
�h�p�h�p�hKh�zh�w
h�*�h|j�hA
�h�*�h�
vh�*�5�h�
vh�M�5�h�
vh�B?5�	h�B?5�h�
vh�9�5�	hK5�2no���e	�	�	


�
�
�
�
�
�
�
��������������������������gd1	
��gdy}bgdVlgd�*��
�
�
�
�
�
�
!">DER�������
��������F
H
N
r
�
�
>M����������������չ���������������|u|��nh�\�h�h�ch�{\h�chVYh�ch^Vh^Vh^VhVYh�i�h�(Sh�ch�h�chExqh�ch�8�h�ch�*�hA
�h�*�	h�p�5�h^Vh_t�h�9�h�
vh�
vh�
v5�h�
vhVl5�h�p�h1	h`Q�h1	5�hVlhVlhVl(	

"���������������������������������������gd�
vgd�*���������LM34�A�st��I������������������������
&Fgd�
vgd�E
&Fgdy}bgd�Rgd�\�gd�
vM123IJKMP��34Pkpqw�st���������������	
!%+-./01��������������Ǵ�����������������������������h�hVY5�h�ch�z�h�i�h�|�h�Zh�ch�{\h_t�h�chVYh�\�h�\�6�hy}bh�\�h�Eh�N�h�\�h�\�0J�j�h�\�h�\�Ujh�\�h�\�Uh�(Sh�\�h�\�51w������IJQ�������BOQ_������'LQ\]p����������������������������ƿƸ�����㸛�����ߏ��������}h�
vh�
v5�\�h�d�h�z�h�|�h�
vh�*�hA
�h�*�h�ch�h�chVYh�ch�
v\�h�ch�*�h�ch�
vh�ch�)h�ch�h�ch^Vh^Vh�N�hQB�h�-Ah^Vh^Vh^Vh3h^Vh�
v0=>?GH�����lmno���2qwxyz�HIJ\cefrst������������ž��������֢���������}�skf	h�|�\�h2a�h2a�\�h�gh�j�5�\�h	(�h�j�5�H*\�h�j�5�\�h�@�5�\�h�:Ph9	hZy�hq rh5?�h�j�hQB�hq rhq r	hq r5�h��5�\�h2	�h�8�5�\�hq r5�\�h�*>h^Vh^Vh^Vh3h^V5�h�
vh�|�h2a�h�
vh�
v(Ix�A���no�yzIJ#$0#1#�$�$p(q(�)������������������������gd�j�gd�5gd�j�gdq rgd^Vgd�*�
&Fgd�
v
&Fgd�
vt|}~�������� !"$FQq������"�"�"	#/#0#�$�$�$ ("(p(q(�)�)�)v*x*y*z*{*������������¾����¶¶����ٯ٫٧��ٖ��}٧�پ���h�ch�c#hD`h�j�CJH*OJQJ^JaJ hD`h�j�CJOJQJ^JaJh�j�h5?�hD`hD`h�@�h�Z�h�|�h�ch�5h�5h�hD`h�j�H*hD`h�j�h�gh�j�5�\�h2a�h3\�	h�|�\�h2a�h2a�\�/�)�)|*}*�.�.�0�0�0o1p1y1�3�3�3�344"4�6�6�6�8�8�8������������������������gd�gd�<gd�gdS6�gd�*�gd�cgd�j�{*|*}*++�+�+�+�+�+�+,,------.-G-`-a-b-e-f-�.�.(0,0g0i0�0�0�0�0�0�0�0�0�0`1n1o1p1y1�1�1�1�1�1�1�1�1�1������������������������쾷շ���շ������������������h�
vh�j�h�
vh�j�5�hA
�h�j�h�j�	h|5�h�7~h�j�5�h�ch|h�ch�c	h�c5�h�ZhD`h�Zh�ch�Zh�}&hD`h3h�Z�h�|�h�5hD`h�j�hD`hD`	h�j�H*5�1�1�1�1�1�122#2b2n2q2�2�2�2�2'3(3-3^3�3�3�3�3�3�3�3�3�3444
444 4"4J6K6�6�6�6�6�8������������������������������´��������x�qh�z�h�h�h�5�\�	h�
�5�h�h�>*CJaJh�h�CJaJh�|�5�CJ\�aJhE$5�CJ\�aJh�h�5�CJ\�aJ	hS6�5�hS6�5�\�hUIh9	hS6�hS6�	h
F�5�hA
�h�j�H*hA
�h�j�h�j�h�
vh�j�h|+�8�8�8�8�8�8�8�8�8�8�8�89�9�9�9�9�9�9�9�9�9�9�9�9�9�9::::8:D:Y:Z:[:^:c:o:q:r:|:~:�:�:�:�:�:�:�:�:�:�:�:�:�:�:�:�:�������������������������������ڹ������������������h�i�mH
sH
h<G�hu;h)�h<G�h�{\h<G�hExqh�i�mHsHh<G�h�i�mHsHh<G�h�i�h�i�	h+oT5�	hExq5�hExqhExq5�	h�5�h�z�h�h�z�:�8�9�9o:p:�:�:h;i;�;�;g<h<==�=�=>>�>�>Z?[?@@@@@@����������������������������gdBI�gd�i��:�:�:�:�:�:�:�:�:�:�:�:�:�:�:;+;6;=;F;G;W;X;Z;^;g;h;i;j;q;r;w;x;�;�;�;�;�;�;�;�;�;�;�;�;�;�;�;�;�;�;�;�����������������������������������������������hrqrmHsHh<G�hr]�mHsHh<G�h�mHsHh<G�hu;hu;h�i�h<G�hExqh<G�h<G�h�{\hrqrhrqrhrqrmH
sH
h<G�hrqrmH
sH
hrqrmH
sH
h<G�h�{\mH
sH
h<G�hExqmH
sH
3�;�;�;�;�;<<<
< <[<\<f<g<h<o<p<u<|<}<�<�<�<�<�<�<�<�<�<�<�<�<�<==�=�=�=�=�=�=�=�=>>>>>&>'>)>.>>>?>L>W>^>_>l>m>w>x>�>�>�>�>�>�>�>�������������ž�ž�ž�������������ɺ������ɬ����������������׬��ɬh<G�h2	�h<G�h<@�h<@�h<G�hrqrhrqrh<G�h��h<G�hExqh<G�h<G�hr]�hrqrmHsHh<G�hr]�mHsHh<G�hrqrmHsHD�>�>�>�>�>8?9?@?A?M?N?[?\?]?k??�?�?�?�?�?�?@@@@@@	@
@@
@@@@@@@@ @!@"@$@%@&@������������������������������������������hUI0JmHnHuh��
h��0Jjh��0JUh41jh41Uh<G�h�z�h<@�h�Z�h)/huY/h<G�h<G�hBI�h<G�h<G�,@	@@@@@@"@#@$@%@&@������������h]�hgd^����&`#$gd�2�,1�h��/ ��=!�"�#��$��%��������D���y������K�vyas.umesh@mayo.edu���y������K�Nmailto:vyas.umesh@mayo.eduyX��;H�,�]ą'c���D���y������K�www.sleepeducation.com���y������K�Vhttp://www.sleepeducation.com/yX��;H�,�]ą'c��^2���� 0@P`p������2(�� 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p������ 0@P`p��8X�V~_HmH	nH	sH	tH	@`�@�*�NormalCJ_HaJmH	sH	tH	Z@Z�:P	Heading 1$���<@&5�CJ KH OJQJ\�^JaJ \@\�:P	Heading 2$���<@& 5�6�CJOJQJ\�]�^JaJDA`�DDefault Paragraph FontVi�VTable Normal :V�4�4�
la�(k �(No List<@�<�*�Comment TextCJaJ�e@��:PHTML Preformatted7
�2�(�
P�x�4 �#\'�*�.2�5@9B*CJOJQJ^JaJph>B@>�8�	Body Text$a$
5�CJ \�6U`�!6	Hyperlink>*B*ph�4 @24^Footer

���!.)@�A.^Page NumberPK!����[Content_Types].xml���N�0E�H���-J��@%�ǎǢ|�ș$�ز�U��L�TB� l,�3��;�r��Ø��J��B+$�G]��7O٭V��<a���(7��I��R�{�pgL�=��r���8�5v&����uQ�뉑8��C����X=��$␴�?6N�JC������F�B.ʹ'�.�+���Y�T���^e5�5�� ��ð�_�g -�;�����Yl�ݎ��|6^�N��`�?���[��PK!�֧�6_rels/.rels���j�0���}Q��%v/��C/�}�(h"���O�
����=������ ����C?�h�v=��Ʌ��%[xp��{۵_�Pѣ<�1�H�0���O�R�Bd���JE�4b$��q_����6L�R�7`������0̞O��,�En7�Li�b��/�S���e��е�����PK!ky���theme/theme/themeManager.xml�M
� @�}�w��7c�(Eb�ˮ��C�AǠҟ����7��՛K
Y,�
�e�.���|,���H�,l����xɴ��I�sQ}#Ր���� ֵ+�!�,�^�$j=�GW��)�E�+&
8���PK!0�C)��theme/theme/theme1.xml�YOo�6��w toc'vu�ر�-M�n�i���P�@�I}��úa��m�a[�إ�4�:lЯ�GR��X^�6؊�>$�������!)O�^�r�C$�y@�����/�yH*��񄴽)�޵��߻��UDb�`}"�qۋ�Jח���X^�)I`n�E���p)���li�V[]�1M<������O�P��6r�=���z�gb�Ig��u��S�eb��O������R�D۫����qu	�g��Z����o~ٺlAp�lx�pT0���+[}`j���zA��V�2�F���i�@�q�v�֬5\|��ʜ̭N��le�X�ds���jcs���7���f����
��W��+�Ն�7����`���g�Ș��J���j|��h(�K��D-����
dX��iJ�؇(��x$(��:��;�˹!�I_�T��S1�����?E��?�����?ZBΪm���U/������?�~����xY���'���y5�g&΋/����ɋ�>���G�M�Ge���D�����3Vq%'#q�����$�8��K�����)f�w9:ĵ��
x}r�x����w���r�:\TZaG�*�y8I�j�bR��c|XŻ�ǿ�I
u3KG�nD1�NIB�s���
��R��u���K>V�.EL+M2�#'�f��i~�V��vl�{u8��z��H�
�*���:�(W�☕
~��J�T�e\O*�tHG��HY��}KN�P�*ݾ˦���TѼ�9/#��A7�qZ��$*c?���qU��n��w�N��%��O��i�4=3��N���)cbJ
u�V�4����(Tn���
7��_?���m-ٛ�{U���B�w�<w���_���$�#��[Ի�8{���(�/�$Ϫ0h݋�F۴��®{L�)#7�i�%�=A�:s�$�),��Qg20pp��f
\}DU4�p
M{��DB��%J������+{�l�C���]��=��5
2F��hsF+��Y��\Ɉ�n�ì��:3���E�[��6�9����`��&45Z!��*��5k8�`Fmw��-��"�d>�z��n���ʜ"Z��x��J�Z��p;�������{/�<�P;��,)''K�Q�k5���q��pN��8�K�Gb�e���
�S��d�̛�\17	�p�a�>��SR!���

3��K4'+�r�zQ
TT��I����Ivt]K�c⫲�K#�v�5+�|��D������~��O@%\w���_�nN[�L��9K���q��g�V�h��n
R!�y+��U�n�;�*&�/H�r��T�	�>��>\
�t��=.Tġ
���S; Z�~�!����P��9gi���C�ڧ!�#	B��,��;�X=ۻ,I�2UW�V�9$l�k���=A��j���;�{�A�P79�|s*Y�����;�̠�[�MC�ۿ�hf��]o��{oY=1k�yV��V���5E8�Vk+֜���\8���0X4D)�!!��?*|f�v�
u���"�x��A�@T_������q��6�4)kڬu�V�7��t�'��%;���i�9s�9�x���,��ڎ-45x�d���8?�ǘ�d�/Y|t��&LIL�J`�& �-G�t�/��PK!
ѐ��'theme/theme/_rels/themeManager.xml.rels��M
�0���wooӺ�&݈Э���5
6?$Q��
�,.�a��i����c2�1h�:�q��m��@RN��;d�`��o7�g�K(M&$R(.1�r'J��ЊT���8��V�"��AȻ�H�u}��|�$�b{��P����8�g/]�QAsم(����#��L�[������PK-!����[Content_Types].xmlPK-!�֧�60_rels/.relsPK-!ky���theme/theme/themeManager.xmlPK-!0�C)���theme/theme/theme1.xmlPK-!
ѐ��'�	theme/theme/_rels/themeManager.xml.relsPK]�
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<a:clrMap xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" bg1="lt1" tx1="dk1" bg2="lt2" tx2="dk2" accent1="accent1" accent2="accent2" accent3="accent3" accent4="accent4" accent5="accent5" accent6="accent6" hlink="hlink" folHlink="folHlink"/>&8h����	$$$'�
M1t{*�1�8�:�;�>&@!#&'(*,-.012�I�)�8@&@"$%)+/3���2I&8X��X�� '!�!����8�@�����������0�(	�
��B
�S����	?����Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z��Z�������``m***�+�+�+B1B1�6�6�6'8
	
����iuu* * *�+�+�+H1H1�6�6�6'8
	
9*�urn:schemas-microsoft-com:office:smarttags�State�8*�urn:schemas-microsoft-com:office:smarttags�City�9*�urn:schemas-microsoft-com:office:smarttags�place�=*�urn:schemas-microsoft-com:office:smarttags	�PlaceName�=
*�urn:schemas-microsoft-com:office:smarttags	�PlaceType�B*�urn:schemas-microsoft-com:office:smarttags�country-region� �urn:schemas:contacts�Sn���S
�1�1�1�1�1�1�1�1�1�1�1�1�1�1�12�3�3�3�3�3�3�3�3�34
4 4888888	888$8'8�m$��1�1�1n2�3L406�6�6�6888888	888$8'83333����
p�������>D������MP	k	p	q	�	�	�	�	

A
A
�
�
����	
-.x���qw	

!$!$�(�(�+�+�+�+,
, ,",�0q2�2�2F3i3j3�3�3L4h4�45�788888888	888$8'8����
o�����>D����P	k	p	q	�	�	�	�	

A
A
�
�
����	
-.qw	

!$!$�+�+
, ,�0q2�2�2i3j3�3�3�788888888	888$8'8:+d(.����������ez"H׀����������2�+��d���������
8��F���������.t8�����������fZH8􀊘����������-�8�N�������������8j|0J���������+I�Q�������������R&�����������X�Wn�����������q�f`������������Gl�o:5����������=�nv������������}$+}�kv���������n;�}��P"����������������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���>*o(()��������^��`���.��p�L��p^�p`�L�.��@����@^�@`���.������^�`���.����L���^��`�L�.��������^��`���.��������^��`���.��P�L��P^�P`�L�.�������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJQJo(���������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJPJQJ^Jo(�h�H-
�������^��`����h�H.
�p����p^�p`����h�H.
�@����@^�@`����h�H.
�����^�`����h�H.
�������^��`����h�H.
�������^��`����h�H.
�������^��`����h�H.
�P����P^�P`����h�H.�������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(�������^��`���o(.�
�����^��`����h�H.�
�p�L�^�p`�L��h�H.�
�@���^�@`����h�H.�
����^�`����h�H.�
���L�^��`�L��h�H.�
�����^��`����h�H.�
�����^��`����h�H.�
�P�L�^�P`�L��h�H.�������^��`���OJQJo(����������^��`���OJQJo(����p����p^�p`���OJQJo(����@����@^�@`���OJQJo(��������^�`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����������^��`���OJQJo(����P����P^�P`���OJQJo(���������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" �������^��`���OJQJo(" ��������^��`���OJQJo(" ��p����p^�p`���OJQJo(" ��@����@^�@`���OJQJo(" ������^�`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��������^��`���OJQJo(" ��P����P^�P`���OJQJo(" n;�}�=�n�2�+}$+}�ez"+I�Q	���R
8�Gl.t8�-�8�X�W:+��8fZH8q�f������������������������@��S�T)#0V؟���������������������������������������������\��$�j����N�>�Q�4�[�j�X���PT����								p(��.�+�FN�h�T�&����j�ʉ2��B�/�ߎ`V�^��
�\��x����4�R�H��V���ț��&��7 ���0�8T�:��$�E.�Jg�wXЬ��*
r%��&��ns�pF�~�/®��n/��|���2NJR��=&��x�!®�D��
<��O|נw>ff�X�4���}�
�(PȖ����yN�.^�8��Ⱥ<�~l								ȳ�U~ mTr�֏|����~\b�l�PHn\������ڎa$�o�B@�p,�����:r�L��b>�-									�R��2�ԣ{�XH&��j�Qr��^|�t`�\~����i�!2G������G�F\O(1��B�"���g"w~ъ$���Ab�Oz9��Xv��^�ʆ�����f�0?�̎��F�h�����6���"�;��u^��>�d�x�p�,9�O)�7_�r:�G��L�~
e��Sac�rj�3L ���SQ'��O)�4�DP pG�	��n�
�
2gA
��S#$�
��SIj�
��S33�O)C!��S���O)�Ru�kN��vP;ap�6i���SwX�DP pB��O)ooh��S�S���S� DP p�:J�n{et�DP p�(��S�XDP p��DP pbT! 3u>;�]�"��S�8�#DP p�U�$�r:s7<%E�%��S�r�&�O)�l�R�%)�O)�]P.�t�yW�03u>;�
2VQ�W�hb3�O)rj�3y�3���Qb4�f�6ac��$P7DP pE	�7�Qb4�r:^4 [3u>;�M\Z&RhB��B��S�C�Y�D3u>;oY�D3u>;hm�E#oj�k�G�u�H7�I��S�#�I��S�]JTTEK�r:H%�KDP p�#L3u>;�kN>�ODP p�9�RDP p�y�R�O)�D�R_f_
�Rh
c`�l�R<anS�r:��SY&PU�=)V�O)VQ�W�=�W��S�N�W��S�M\Z^4 [5�^�O)_f_h
c`I�`s7<%vP;a�a�r:�A4b3u>;n�c�L�~�n{e�o�h��S�6i#oj�l�O)VA�mDP p`T@n�L�~�[�n��n��{�U3o�L�~�`�o�k�GDP pY&PUykp�O)3	r�[�n|tsDP p�C�w�t�y��{~�|��S,w�}�C�w�L�~�u�Hm�~�O)��DP p~�}�)�ZK�5�]��)�w
^LtmJ
9	�c��R|1	Rm!2#E$�u%�}&N'�&-)/uY/�141c13�&3u;�<�*>�B?�-A�EUI�"K�CL�:P�(S+oT^VVY�{\<]D`y}ba~d;e�"fVly^mExqq r^Nrrqr�t�
v�jw8qw�z
8|�7~�]��y�U��F�� ��2a����p�{��
�r]�
F�Zy�)�_t����B��z�fV��8�|j�V'��N�<G��m�`Q�QB����s��@�2	�<@��UV�ni��M��R��S��Z���:��9��*��i��|�S6��j�	"��b��d��2�v9�5?�BI��\��u��N��|�88�@��7�7�7�7&8�@��Unknown������������G��*�Ax�	�Times New Roman5��Symbol3.��*�Cx�	�Arial?=�	�*�Cx�	�Courier New;��WingdingsA���$B�Cambria Math"����hU�&�|A[�/e[�/e!������24�7�73�q���HP�?�����������������������*�2!xx����Children's Health SystemUmesh K VyasL	

����Oh��+'��0t�������	
0<
HT\dl�Children's Health SystemNormal.dotmUmesh K Vyas65Microsoft Office Word@��n@�}J��@lz����[�/����՜.��+,��D��՜.��+,��Php��������
���(Children's Hospital and Health Systeme�7Title, 8@_PID_HLINKS�A�!?http://www.sleepeducation.com/fmailto:vyas.umesh@mayo.edu	

 !"#$%&'()*+,-./01234����6789:;<����>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcdefghij����lmnopqr����tuvwxyz��������}������������Root Entry��������	�F��������Data
������������51Table����=5[WordDocument����.hSummaryInformation(������������kDocumentSummaryInformation8��������sCompObj������������r������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������
����	�F Microsoft Word 97-2003 Document
MSWordDocWord.Document.8�9�q

Youez - 2016 - github.com/yon3zu
LinuXploit