Regiochemical studies for nucleophilic addition on allylic acetate cycloheptyne cobalt complexes and the progression towards the synthesis of 7,5-bicyclic ring systems containing the cobalt complex.

There are several naturally occurring compounds that have fused 7,5-bicyclic ring systems. This thesis will focus on approaches to synthesizing 7,5-bicyclic systems containing a dicobalt hexacarbonyl complex. In this context, the allylic acetate cycloheptenyne complex (66) was reacted with various carbon- and hetero-based nucleophiles to determine the regiochemistry of the substitution. The gamma to alpha ratio for carbon-based nucleophiles were approximately 4:1, while hetero-based nucleophiles were 100% gamma. Once the ratios were established, several of these product compounds, which contained an electrophilic site, were investigated for further reaction to form the additional ring (Scheme 28). Formation of a 7,5-bicyclic ketone 131, alcohol 132 and diol 133 were observed when compound 129 was mixed with boron trifluoride (Scheme 42).Dept. of Chemistry and Biochemistry. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis2004 .D56. Source: Masters Abstracts International, Volume: 43-01, page: 0218. Thesis (M.Sc.)--University of Windsor (Canada), 2004

Lewis and protic acid mediated Nicholas reactions of 3-acetoxycyclohept-1-en-4-ynedicobalt hexacarbonyl: site selectivity of nucleophile incorporation

Nicholas reactions on the cation derived from the cyclic allylic acetate alkynedicobalt complex 1 favour the gamma-site kinetically for most nucleophiles, with increasing amounts of of-products in cases with greater nucleophilicity. Some regiocontrol in introduction of a specific nucleophilic fragment is possible by using different nucleophiles. Under conditions where reversibility is possible, the thermodynamically favoured site is exclusively gamma-. (c) 2005 Elsevier Ltd. All rights reserved

Towards Non-Invasive Monitoring of Hypovolemia in Intensive Care Patients

Hypovolemia caused by internal hemorrhage is a major cause of death in critical care patients. However, hypovolemia is difficult to diagnose in a timely fashion, as obvious symptoms do not manifest until patients are already nearing a critical state of shock. Novel non-invasive methods for detecting hypovolemia in the literature utilize the photoplethysmogram (PPG) waveform generated by the pulse-oximeter attached to a finger or ear. Until now, PPG-based alarms have been evaluated only on healthy patients under ideal testing scenarios (e.g., motionless patients); however, the PPG is sensitive to patient health and significant artifacts manifest when patients move. Since patient health varies within the intensive care unit (ICU) and ICU patients typically do not remain motionless, this work introduces a PPG-based monitor designed to be robust to waveform artifacts and health variability in the underlying patient population. To demonstrate the promise of our approach, we evaluate the proposed monitor on a small sample of intensive care patients from the Physionet database. The monitor detects hypovolemia within a twelve hour window of nurse documentation of hypovolemia when it is present, and achieves a low false alarm rate over patients without documented hypovolemia

Robust Monitoring of Hypovolemia in Intensive Care Patients Using Photoplethysmogram Signals

The paper presents a fingertip photoplethysmography based technique to assess patient fluid status that is robust to waveform artifacts and health variability in the underlying patient population. The technique is intended for use in intensive care units, where patients are at risk for hypovolemia, and signal artifacts and inter-patient variations in health are common. Input signals are preprocessed to remove artifact, then a parameter-invariant statistic is calculated to remove effects of patient-specific physiology. Patient data from the Physionet MIMICII database was used to evaluate the performance of this technique. The proposed method was able to detect hypovolemia within 24 hours of onset in all hypovolemic patients tested, while producing minimal false alarms over non-hypovolemic patients

Clinician-in-the-Loop Annotation of ICU Bedside Alarm Data

In this work, we describe the state of clinical monitoring in the intensive care unit and operating room, where patients are at their most fragile and thus monitoring is most heightened. We describe how large amounts of data generated by monitoring patients’ physiologic signals, along with the ubiquitous aspecific threshold alarms in use today, cause dangerous alarm fatigue for medical caregivers. In order to build more specific, more useful alarms, we gathered a novel data set that would allow us to assess the number, types, and utility of alarms currently in use in the intensive care unit. To do this, we developed a system to collect physiologic monitor data, alarms, and annotations of those alarms provided electronically by clinicians. We describe the collection process for this novel data set and provide a preliminary description of the data

Blind trials of computer-assisted structure elucidation software

<p>Abstract</p> <p>Background</p> <p>One of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an <it>in silico </it>structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments.</p> <p>Results</p> <p>Beginning in 2003, and for the following nine years, the algorithms and software technology contained within ACD/Structure Elucidator have been tested against 112 data sets; many of these were unique challenges. Of these challenges 9% were double-blind trials. The results of eighteen of the single-blind trials were investigated in detail and included problems of a diverse nature with many of the specific challenges associated with algorithmic structure elucidation such as deficiency in protons, structure symmetry, a large number of heteroatoms and poor quality spectral data.</p> <p>Conclusion</p> <p>When applied to a complex set of blind trials, ACD/Structure Elucidator was shown to be a very useful tool in advancing the computer's contribution to elucidating a candidate structure from a set of spectral data (NMR and MS) for an unknown. The synergistic interaction between humans and computers can be highly beneficial in terms of less biased approaches to elucidation as well as dramatic improvements in speed and throughput. In those cases where multiple candidate structures exist, ACD/Structure Elucidator is equipped to validate the correct structure and eliminate inconsistent candidates. Full elucidation can generally be performed in less than two hours; this includes the average spectral data processing time and data input.</p