Abstract:
Objectives To identify demographic, clinical and laboratory risk factors for death due to dengue fever in adult patients in Singapore. Methods Multi-center retrospective study of hospitalized adult patients with confirmed dengue fever in Singapore between 1 January 2004 and 31 December 2008. Non-fatal controls were selected by matching age and year of infection with fatal cases. World Health Organization 1997, 2009 criteria were applied to define dengue hemorrhagic fever (DHF), warning signs and severe dengue. Statistical significance was assessed by conditional logistic regression modeling. Results Significantly more fatal cases than matched controls had pre-existing co-morbid conditions, and presented with abdominal pain/tenderness. Median pulse rates were significantly higher while myalgia was significantly less frequent in cases. . Fatal cases also had higher leucocyte counts, platelet counts, serum sodium, potassium, urea, creatine and bilirubin levels on admission compared to controls. There was no statistical significant difference between the prevalence of DHF and hematocrit level among cases and controls. Multivariate analysis showed myalgia and leucocyte count at presentation were independent predictors of fatality (adjusted odds ratios 0.09 and 2.94 respectively). None of the controls was admitted to intensive care unit (ICU) or given blood transfusion, while 71.4% and 28.6% of fatal cases received ICU admission and blood transfusion. Conclusions Absence of myalgia and leucocytosis on admission were independently associated with fatality in our matched case-control study. Fatalities were also commonly associated with co-morbidities and clinicians should be alarmed if dengue patients fulfilled severe dengue case definition on admission.

Abstract:
We conducted a multi-center retrospective chart review of all confirmed adult dengue deaths in Singapore from 1 January 2004 to 31 December 2008.Of 28 adult dengue deaths, median age was 59 years. Male gender comprised 67.9% and co-morbidities existed in 75%. From illness onset, patients presented for admission at a median of 4 days and death occurred at a median of 12 days. Intensive care admission was required in 71.4%. Probable dengue was diagnosed in 32.1% by WHO 1997 criteria and 78.6% by WHO 2009. The earliest warning sign was persistent vomiting at a median of 1.5 days. Hematocrit change ≥20% concurrent with platelet count <20 × 10^9/L was associated with the shortest interval to death at a median of 3 days. Only 35.7% of death cases fulfilled DHF criteria by WHO 1997 versus severe dengue in 100.0% by WHO 2009 criteria. Deaths were due to shock and organ failure. Acute renal impairment occurred in 71.4%, impaired consciousness 57.1% and severe hepatitis 53.6%.In our adult fatal dengue cohort, WHO 2009 criteria had higher sensitivity in diagnosing probable dengue and severe dengue compared with WHO 1997. As warning signs, persistent vomiting occurred early and hematocrit change ≥20% concurrent with platelet count <20 × 10^9/L preceded death most closely.Dengue is the most important arthropod-borne viral disease in humans. The World Health Organization (WHO) has estimated that 1.8 billion people, or more than 70% of the global at-risk population, live in the WHO Southeast Asia and the Western Pacific regions which account for nearly 75% of current global disease burden from dengue [1]. Singapore, a developed island city-state in Southeast Asia has experienced resurgent dengue epidemics since the 1990s after previous decades of vector control effectively reduced the Aedes house index [2]. In addition, dengue infections in Singapore in recent years have shifted from primarily a childhood disease to that of adults [2]. With this resurgence, the classification of d

Abstract:
Background Dengue is re-emerging throughout the tropical world, causing frequent recurrent epidemics. The initial clinical manifestation of dengue often is confused with other febrile states confounding both clinical management and disease surveillance. Evidence-based triage strategies that identify individuals likely to be in the early stages of dengue illness can direct patient stratification for clinical investigations, management, and virological surveillance. Here we report the identification of algorithms that differentiate dengue from other febrile illnesses in the primary care setting and predict severe disease in adults. Methods and Findings A total of 1,200 patients presenting in the first 72 hours of acute febrile illness were recruited and followed up for up to a 4-week period prospectively; 1,012 of these were recruited from Singapore and 188 from Vietnam. Of these, 364 were dengue RT-PCR positive; 173 had dengue fever, 171 had dengue hemorrhagic fever, and 20 had dengue shock syndrome as final diagnosis. Using a C4.5 decision tree classifier for analysis of all clinical, haematological, and virological data, we obtained a diagnostic algorithm that differentiates dengue from non-dengue febrile illness with an accuracy of 84.7%. The algorithm can be used differently in different disease prevalence to yield clinically useful positive and negative predictive values. Furthermore, an algorithm using platelet count, crossover threshold value of a real-time RT-PCR for dengue viral RNA, and presence of pre-existing anti-dengue IgG antibodies in sequential order identified cases with sensitivity and specificity of 78.2% and 80.2%, respectively, that eventually developed thrombocytopenia of 50,000 platelet/mm3 or less, a level previously shown to be associated with haemorrhage and shock in adults with dengue fever. Conclusion This study shows a proof-of-concept that decision algorithms using simple clinical and haematological parameters can predict diagnosis and prognosis of dengue disease, a finding that could prove useful in disease management and surveillance.

Abstract:
Background Dengue virus is transmitted by mosquitoes and has four serotypes. Cross-protection to other serotypes lasting for a few months is observed following infection with one serotype. There is evidence that low-affinity T and/or B cells from primary infections contribute to the severe syndromes often associated with secondary dengue infections. such pronounced immune-mediated enhancement suggests a dengue-specific pattern of immune cell activation. This study investigates the acute and early convalescent B cell response leading to the generation of cross-reactive and neutralizing antibodies following dengue infection. Methodology/Principal Findings We assayed blood samples taken from dengue patients with primary or secondary infection during acute disease and convalescence and compared them to samples from patients presenting with non-dengue related fever. Dengue induced massive early plasmablast formation, which correlated with the appearance of polyclonal, cross-reactive IgG for both primary and secondary infection. Surprisingly, the contribution of IgG to the neutralizing titer 4–7 days after fever onset was more than 50% even after primary infection. Conclusions/Significance Poly-reactive and virus serotype cross-reactive IgG are an important component of the innate response in humans during both primary and secondary dengue infection, and “innate specificities” seem to constitute part of the adaptive response in dengue. While of potential importance for protection during secondary infection, cross-reactive B cells will also compete with highly neutralizing B cells and possibly interfere with their development.

Abstract:
The group E(3)=SO(3) *s T(3), that is the homogeneous subgroup of the Galilei group parameterized by rotation angles and velocities, defines the continuous group of transformations between the frames of inertial particles in Newtonian mechanics. We show in this paper that the continuous group of transformations between the frames of noninertial particles following trajectories that satisfy Hamilton's equations is given by the Hamilton group Ha(3)=SO(3) *s H(3) where H(3) is the Weyl-Heisenberg group that is parameterized by rates of change of position, momentum and energy, i.e. velocity, force and power. The group E(3) is the inertial special case of the Hamilton group.

Abstract:
Physical states in quantum mechanics are rays in a Hilbert space. Projective representations of a relativity group transform between the quantum physical states that are in the admissible class. The physical observables of position, time, energy and momentum are the Hermitian representation of the Weyl-Heisenberg algebra. We show that there is a consistency condition that requires the relativity group to be a subgroup of the group of automorphisms of the Weyl-Heisenberg algebra. This, together with the requirement of the invariance of classical time, results in the inhomogeneous Hamilton group that is the relativity group for noninertial frames in classical Hamilton's mechanics. The projective representation of a group is equivalent to unitary representations of its central extension. The central extension of the inhomogeneous Hamilton group and its corresponding Casimir invariants are computed. One of the Casimir invariants is a generalized spin that is invariant for noninertial states. It is the familiar inertial Galilean spin with additional terms that may be compared to noninertial experimental results.

Abstract:
Born proposed a unification of special relativity and quantum mechanics that placed position, time, energy and momentum on equal footing through a reciprocity principle and extended the usual position-time and energy-momentum line elements to this space by combining them through a new fundamental constant. Requiring also invariance of the symplectic metric yields U(1,3) as the invariance group, the inhomogeneous counterpart of which is the canonically relativistic group CR(1,3) = U(1,3) *s H(1,3) where H(1,3) is the Heisenberg Group in 4 dimensions and "*s" is the semidirect product. This is the counterpart in this theory of the Poincare group and reduces in the appropriate limit to the expected special relativity and classical Hamiltonian mechanics transformation equations. This group has the Poincare group as a subgroup and is intrinsically quantum with the Position, Time, Energy and Momentum operators satisfying the Heisenberg algebra. The representations of the algebra are studied and Casimir invariants are computed. Like the Poincare group, it has a little group for a ("massive") rest frame and a null frame. The former is U(3) which clearly contains SU(3) and the latter is Os(2) which contains SU(2)*U(1).

Abstract:
The maximal symmetry of a quantum system with Heisenberg commutation relations is given by the projective representations of the automorphism group of the Weyl-Heisenberg algebra. The automorphism group is the central extension of the inhomogeneous symplectic group with a conformal scaling that acts on extended phase space. We determine the subgroup that also leaves invariant a degenerate orthogonal Minkowski line element. This defines noninertial relativistic symmetry transformations that have the expected classical limit as c becomes infinite.

Abstract:
The Hilbert space of the unitary irreducible representations of a Lie group that is a quantum dynamical group are identified with the quantum state space. Hermitian representation of the algebra are observables. The eigenvalue equations for the representation of the set of Casimir invariant operators define the field equations of the system. A general class of dynamical groups are semidirect products K *s N for which the representations are given by Mackey's theory. The homogeneous group K must be a subgroup of the automorphisms of the normal group N. The archetype dynamical group is the Poincare group. The field equations defined by the representations of the Casimir operators define the basic equations of physics; Klein-Gordon, Dirac, Maxwell and so forth. This paper explores a more general dynamical group candidate that is also a semi-direct product but where the 'translation' normal subgroup N is now the Heisenberg group. The relevant automorphisms of the Heisenberg group are the symplectic group. This together with the requirement for an orthogonal metric leads to the pseudo-unitary group for the homogeneous group K. The physical meaning and motivation of this group, called the quaplectic group, is presented and the Hermitian irreducible representations of the algebra are determined. As with the Poincare group, choice of the group defines the Hilbert space of representations that are identified with quantum particle states. The field equations that are the eigenvalue equations for the representation of the Casimir operators, are obtained and investigated. The theory embodies the Born reciprocity principle and a new relativity principle.

Abstract:
We present a new derivation of Hamilton's equations that shows that they have a symmetry group Sp(2n) *s H(n). Sp(2n) is the symplectic group and H(n) is mathematically a Weyl-Heisenberg group that is parameterized by velocity, force and power where power is the central element of the group. We present a new derivation of Hamilton's equations that shows that they have a symmetry group Sp(2n) *s H(n). The group Sp(2n) is the real noncompact symplectic group and H(n) is mathematically a Weyl-Heisenberg group that is parameterized by velocity, force and power where power is the central element of the group. The homogeneous Galilei group SO(n) *s A(n), where the special orthogonal group SO(n) is parameterized by rotations and the abelian group A(n)is parameterized by velocity, is the inertial subgroup.