A systematic mid-infrared spectroscopic study of thermally processed H2S ices.

The positive identification of the molecular components of interstellar icy grain mantles is critically reliant upon the availability of laboratory-generated mid-infrared absorption spectra which can be compared against data acquired by ground- and space-borne telescopes. However, one molecule which remains thus far undetected in interstellar ices is H2S, despite its important roles in astrochemical and geophysical processes. Such a lack of a detection is surprising, particularly in light of its relative abundance in cometary ices which are believed to be the most pristine remnants of pre-solar interstellar ices available for study. In this paper, we present the results of an extensive and quantitative mid-infrared spectroscopic characterisation of H2S ices deposited at 20, 40, and 70 K and thermally processed to sublimation in an ultrahigh-vacuum system. We anticipate our results to be useful in confirming the detection of interstellar H2S ice using high-resolution and high-sensitivity instruments such as the James Webb Space Telescope, as well as in the identification of solid H2S in icy environments in the outer Solar System, such as comets and moons.

Infrared Spectral Signatures of Nucleobases in Interstellar Ices I: Purines.

The purine nucleobases adenine and guanine are complex organic molecules that are essential for life. Despite their ubiquitous presence on Earth, purines have yet to be detected in observations of astronomical environments. This work therefore proposes to study the infrared spectra of purines linked to terrestrial biochemical processes under conditions analogous to those found in the interstellar medium. The infrared spectra of adenine and guanine, both in neat form and embedded within an ice made of H2O:NH3:CH4:CO:CH3OH (10:1:1:1:1), were analysed with the aim of determining which bands attributable to adenine and/or guanine can be observed in the infrared spectrum of an astrophysical ice analogue rich in other volatile species known to be abundant in dense molecular clouds. The spectrum of adenine and guanine mixed together was also analysed. This study has identified three purine nucleobase infrared absorption bands that do not overlap with bands attributable to the volatiles that are ubiquitous in the dense interstellar medium. Therefore, these three bands, which are located at 1255, 940, and 878 cm-1, are proposed as an infrared spectral signature for adenine, guanine, or a mixture of these molecules in astrophysical ices. All three bands have integrated molar absorptivity values (ψ) greater than 4 km mol-1, meaning that they should be readily observable in astronomical targets. Therefore, if these three bands were to be observed together in the same target, then it is possible to propose the presence of a purine molecule (i.e., adenine or guanine) there.

A systematic mid-infrared spectroscopic study of thermally processed SO2 ices.

The use of mid-infrared spectroscopy to characterise the chemistry of icy interstellar and Solar System environments will be exploited in the near future to better understand the chemical processes and molecular inventories in various astronomical environments. This is, in part, due to observational work made possible by the recently launched James Webb Space Telescope as well as forthcoming missions to the outer Solar System that will observe in the mid-infrared spectroscopic region (e.g., the Jupiter Icy Moons Explorer and the Europa Clipper missions). However, such spectroscopic characterisations are crucially reliant upon the generation of laboratory data for comparative purposes. In this paper, we present an extensive mid-infrared characterisation of SO2 ice condensed at several cryogenic temperatures between 20 and 100 K and thermally annealed to sublimation in an ultrahigh-vacuum system. Our results are anticipated to be useful in confirming the detection (and possibly thermal history) of SO2 on various Solar System bodies, such as Ceres and the icy Galilean moons of Jupiter, as well as in interstellar icy grain mantles.

Energetic electron irradiations of amorphous and crystalline sulphur-bearing astrochemical ices.

Laboratory experiments have confirmed that the radiolytic decay rate of astrochemical ice analogues is dependent upon the solid phase of the target ice, with some crystalline molecular ices being more radio-resistant than their amorphous counterparts. The degree of radio-resistance exhibited by crystalline ice phases is dependent upon the nature, strength, and extent of the intermolecular interactions that characterise their solid structure. For example, it has been shown that crystalline CH3OH decays at a significantly slower rate when irradiated by 2 keV electrons at 20 K than does the amorphous phase due to the stabilising effect imparted by the presence of an extensive array of strong hydrogen bonds. These results have important consequences for the astrochemistry of interstellar ices and outer Solar System bodies, as they imply that the chemical products arising from the irradiation of amorphous ices (which may include prebiotic molecules relevant to biology) should be more abundant than those arising from similar irradiations of crystalline phases. In this present study, we have extended our work on this subject by performing comparative energetic electron irradiations of the amorphous and crystalline phases of the sulphur-bearing molecules H2S and SO2 at 20 K. We have found evidence for phase-dependent chemistry in both these species, with the radiation-induced exponential decay of amorphous H2S being more rapid than that of the crystalline phase, similar to the effect that has been previously observed for CH3OH. For SO2, two fluence regimes are apparent: a low-fluence regime in which the crystalline ice exhibits a rapid exponential decay while the amorphous ice possibly resists decay, and a high-fluence regime in which both phases undergo slow exponential-like decays. We have discussed our results in the contexts of interstellar and Solar System ice astrochemistry and the formation of sulphur allotropes and residues in these settings.

Ozone production in electron irradiated CO2:O2 ices.

The detection of ozone (O3) in the surface ices of Ganymede, Jupiter's largest moon, and of the Saturnian moons Rhea and Dione, has motivated several studies on the route of formation of this species. Previous studies have successfully quantified trends in the production of O3 as a result of the irradiation of pure molecular ices using ultraviolet photons and charged particles (i.e., ions and electrons), such as the abundances of O3 formed after irradiation at different temperatures or using different charged particles. In this study, we extend such results by quantifying the abundance of O3 as a result of the 1 keV electron irradiation of a series of 14 stoichiometrically distinct CO2:O2 astrophysical ice analogues at 20 K. By using mid-infrared spectroscopy as our primary analytical tool, we have also been able to perform a spectral analysis of the asymmetric stretching mode of solid O3 and the variation in its observed shape and profile among the investigated ice mixtures. Our results are important in the context of better understanding the surface composition and chemistry of icy outer Solar System objects, and may thus be of use to future interplanetary space missions such as the ESA Jupiter Icy Moons Explorer and the NASA Europa Clipper missions, as well as the recently launched NASA James Webb Space Telescope.

Comparative electron irradiations of amorphous and crystalline astrophysical ice analogues.

Laboratory studies of the radiation chemistry occurring in astrophysical ices have demonstrated the dependence of this chemistry on a number of experimental parameters. One experimental parameter which has received significantly less attention is that of the phase of the solid ice under investigation. In this present study, we have performed systematic 2 keV electron irradiations of the amorphous and crystalline phases of pure CH3OH and N2O astrophysical ice analogues. Radiation-induced decay of these ices and the concomitant formation of products were monitored in situ using FT-IR spectroscopy. A direct comparison between the irradiated amorphous and crystalline CH3OH ices revealed a more rapid decay of the former compared to the latter. Interestingly, a significantly lesser difference was observed when comparing the decay rates of the amorphous and crystalline N2O ices. These observations have been rationalised in terms of the strength and extent of the intermolecular forces present in each ice. The strong and extensive hydrogen-bonding network that exists in crystalline CH3OH (but not in the amorphous phase) is suggested to significantly stabilise this phase against radiation-induced decay. Conversely, although alignment of the dipole moment of N2O is anticipated to be more extensive in the crystalline structure, its weak attractive potential does not significantly stabilise the crystalline phase against radiation-induced decay, hence explaining the smaller difference in decay rates between the amorphous and crystalline phases of N2O compared to those of CH3OH. Our results are relevant to the astrochemistry of interstellar ices and icy Solar System objects, which may experience phase changes due to thermally-induced crystallisation or space radiation-induced amorphisation.

The Ice Chamber for Astrophysics-Astrochemistry (ICA): A new experimental facility for ion impact studies of astrophysical ice analogs.

The Ice Chamber for Astrophysics-Astrochemistry (ICA) is a new laboratory end station located at the Institute for Nuclear Research (Atomki) in Debrecen, Hungary. The ICA has been specifically designed for the study of the physico-chemical properties of astrophysical ice analogs and their chemical evolution when subjected to ionizing radiation and thermal processing. The ICA is an ultra-high-vacuum compatible chamber containing a series of IR-transparent substrates mounted on a copper holder connected to a closed-cycle cryostat capable of being cooled down to 20 K, itself mounted on a 360° rotation stage and a z-linear manipulator. Ices are deposited onto the substrates via background deposition of dosed gases. The ice structure and chemical composition are monitored by means of FTIR absorbance spectroscopy in transmission mode, although the use of reflectance mode is possible by using metallic substrates. Pre-prepared ices may be processed in a variety of ways. A 2 MV Tandetron accelerator is capable of delivering a wide variety of high-energy ions into the ICA, which simulates ice processing by cosmic rays, solar wind, or magnetospheric ions. The ICA is also equipped with an electron gun that may be used for electron impact radiolysis of ices. Thermal processing of both deposited and processed ices may be monitored by means of both FTIR spectroscopy and quadrupole mass spectrometry. In this paper, we provide a detailed description of the ICA setup as well as an overview of the preliminary results obtained and future plans.

The Effects of Sex-Type, the Sex of the Avatar, and Salience of the Sex of the Avatar on Emotional Valence and Arousal.

The objective of this study was to investigate the effects of avatar sex, salience of avatar sex, and player sex-type on less conscious embodied emotional arousal and valence vs. consciously perceived emotional arousal and valence elicited by a gaming experience. The experiment conducted a 2 avatar sex (female × male) × 2 salience of avatar sex (high × low) × 2 player sex-type (sex-typed × non-sex-typed) mixed model factorial design. Participants were randomly assigned to one of two gameplay conditions (high-salience male and female avatar or low-salience male and female avatar) and then played two 15-min sessions of a video game-one session playing the game as a male avatar and one session playing the game as a female avatar. The order in which participants played as either a male or female avatar was randomized. Psychophysiological indicators of arousal (skin conductance) and valence (facial electromyography) were recorded during gameplay. Self-report measures of arousal and valence were obtained immediately after each 15-min session of gameplay. Data analysis tested hypotheses concerning the effects of avatar sex, salience of avatar sex, and player sex-type separately on real-time embodied variation in arousal and valence as revealed through physiological indicators and conscious perception of arousal and valence obtained through self-report measures.

A preliminary study into the use of tree-ring and foliar geochemistry as bio-indicators for vehicular NOx pollution in Malta.

Emissions from traffic over the past few decades have become a significant source of air pollution. Among the pollutants emitted are nitrogen oxides (NOx), exposure to which can be detrimental to public health. Recent studies have shown that nitrogen (N) stable isotope ratios in tree-rings and foliage express a fingerprint of their major N source, making them appropriate for bio-monitoring purposes. In this study, we have applied this proxy to Aleppo pines (Pinus halepensis) at three distances from one of the busiest roads in Malta, a country known to suffer from intense traffic pollution. Our results showed that N and organic carbon (C) stable isotope ratios in tree-rings do not vary over the period 1980-2018 at any of the investigated sites; however, statistically significant spatial trends were apparent in both tree-rings and foliage. The roadside and transitional sites exhibited more positive δ15N and more negative δ13C values compared to those at a rural control site. This is likely due to the incorporation of 15N-enriched NOx and 13C-depleted CO2 from traffic pollution. Sampled top-soil also exhibited the δ15N trend. Our results constitute the first known application of dendrogeochemistry to atmospheric pollution monitoring in Malta.

Does this treatment work for me? The patient's role in assessing medical care.

Randomised clinical trials are designed to determine whether a particular treatment is appropriate to make a significant difference to the health of a defined population and to aid its approval for use. For an accurate, cheap and simple assessment to see if a treatment benefits an individual person, all that is needed is a pen, paper, simple pocket calculator and daily recording of a few variables. It requires the ability to read and write and to understand addition and division. Factorial design of experiments is used to show the impact of several variables and their interaction on the person's health status. An example of a 75-year-old man with an enlarged prostate is used here to illustrate this approach. This person was able to understand and reduce side effects, lower the costs of medication by 83% and improve measured health status by 28%. A multivariate model for this person was then created with about 450 person-days of data.

Autonomic components of Complex Regional Pain Syndrome (CRPS) are favourably affected by Electrical Twitch-Obtaining Intramuscular Stimulation (ETOIMS): effects on blood pressure and heart rate.

INTRODUCTION: Favourable pain relief results on evoking autonomous twitches at myofascial trigger points with Electrical Twitch Obtaining Intramuscular Stimulation (ETOIMS). AIM: To document autonomic nervous system (ANS) dysfunction in Complex Regional Pain Syndrome (CRPS) from blood pressure (BP) and pulse/heart rate changes with ETOIMS. METHODS AND MATERIALS: A patient with persistent pain regularly received serial ETOIMS sessions of 60, 90, 120 or ≥150 min over 24 months. Outcome measures include BP: systolic, diastolic, pulse pressure and pulse/heart rate, pre-session/immediate-post-session summed differences (SDPPP index), and pain reduction. His results were compared with that of two other patients and one normal control. Each individual represented the following maximal elicitable twitch forces (TWF) graded 1-5: maximum TWF2: control subject; maximum TWF3: CRPS patient with suspected ANS dysfunction; and maximum TWF4 and TWF5: two patients with respective slow-fatigue and fast-fatigue twitches who during ETOIMS had autonomous twitching at local and remote myotomes simultaneously from denervation supersensitivity. ETOIMS results between TWFs were compared using one-way analysis of variance test. RESULTS: The patients showed immediate significant pain reduction, BP and pulse/heart rate changes/reduction(s) except for diastolic BP in the TWF5 patient. TWF2 control subject had diastolic BP reduction with ETOIMS but not with rest. Linear regression showed TWF grade to be the most significant variable in pain reduction, more so than the number of treatments, session duration and treatment interval. TWF grade was the most important variable in significantly reducing outcome measures, especially pulse/heart rate. Unlike others, the TWF3 patient had distinctive reductions in SDPPP index. CONCLUSIONS: Measuring BP and pulse/heart rate is clinically practical for alerting ANS dysfunction maintained CRPS. SDPPP index (≥26) and pulse/heart rate (≥8) reductions with almost every ETOIMS treatment, plus inability to evoke autonomous twitches due to pain-induced muscle hypertonicity, are pathognomonic of this problem.

A systematic review and meta-analysis of screen time behaviour among North American indigenous populations.

Screen time (computer, television, video game and smartphone/tablet activity) is associated with increased obesity and other health risks. This systematic review evaluates screen time among North American Indigenous populations and compares it with that of North American Europeans. Electronic databases (e.g. MEDLINE and EMBASE) were searched, and citations cross-referenced. Included articles reported screen time among First Nations/American Indians, Métis, Inuit/Alaskan Natives or Native Hawaiians. From 788 citations evaluated, 40 identified articles report television, video game, computer and/or overall screen time. Overall screen time was 3.65 ± 1.26 h day(-1) (n = 2,242, 8 articles) among Indigenous children/youth and 3.61 ± 2.95 h day(-1) (n = 155, 1 article) among adults. Among children/youth, 66.0% (n = 11 256, 9 articles) reported less than 2 h day(-1) of television screen time, while only 52.8% (n = 2,458, 1 article) of adults reported this volume. Screen time was generally greater among male population, youth, First Nations/American Indians and overweight/obese individuals. Indigenous children/youth reported greater overall screen time than North American Europeans (4.81 ± 2.84 h day(-1) , n = 1,182 vs. 3.40 ± 2.81 h day(-1) , n = 2,785; 3 articles; p < 0.0001). Screen time is common among North American Indigenous populations. Further research evaluating interventions to reduce screen time and chronic disease risks is required.

Advancing the science of patient safety.

Despite a decade's worth of effort, patient safety has improved slowly, in part because of the limited evidence base for the development and widespread dissemination of successful patient safety practices. The Agency for Healthcare Research and Quality sponsored an international group of experts in patient safety and evaluation methods to develop criteria to improve the design, evaluation, and reporting of practice research in patient safety. This article reports the findings and recommendations of this group, which include greater use of theory and logic models, more detailed descriptions of interventions and their implementation, enhanced explanation of desired and unintended outcomes, and better description and measurement of context and of how context influences interventions. Using these criteria and measuring and reporting contexts will improve the science of patient safety.

Testing models of facultative sex ratio adjustment in the pollinating fig wasp Platyscapa awekei.

Female hymenoptera are renowned for their ability to adjust offspring sex ratio to local mate competition. When two females share a patch, they frequently produce clutches that differ in size, the female with the larger clutch optimally producing a more female-biased sex ratio and vice versa. Females can base their sex allocation on their own clutch size only ("self-knowledge") or on both females' clutch sizes ("complete knowledge"). Few studies have genotyped offspring so that each mother's contribution can be considered separately while none has found that both sources of information are used simultaneously. We genotyped 2489 wasps from 28 figs and assigned their maternity to one of the two foundress females. We argue that likelihood is a very convenient method to compare alternative models, while fitness calculations help to appreciate the cost of maladaptation. We find that the pollinating fig wasp Platyscapa awekei simultaneously uses its own as well as the other females clutch size in allocating sex. Indeed, the complete knowledge model explains the data 36 times better than the self-knowledge model. However, large clutches contained fewer males than the optimal predictions leading to a median selection coefficient of 0.01.

Adherence to surgical care improvement project measures and the association with postoperative infections.

CONTEXT: The Surgical Care Improvement Project (SCIP) aims to reduce surgical infectious complication rates through measurement and reporting of 6 infection-prevention process-of-care measures. However, an association between SCIP performance and clinical outcomes has not been demonstrated. OBJECTIVE: To examine the relationship between SCIP infection-prevention process-of-care measures and postoperative infection rates. DESIGN, SETTING, PARTICIPANTS: A retrospective cohort study, using Premier Inc's Perspective Database for discharges between July 1, 2006 and March 31, 2008, of 405 720 patients (69% white and 11% black; 46% Medicare patients; and 68% elective surgical cases) from 398 hospitals in the United States for whom SCIP performance was recorded and submitted for public report on the Hospital Compare Web site. Three original infection-prevention measures (S-INF-Core) and all 6 infection-prevention measures (S-INF) were aggregated into 2 separate all-or-none composite scores. Hierarchical logistical models were used to assess process-of-care relationships at the patient level while accounting for hospital characteristics. MAIN OUTCOME MEASURE: The ability of reported adherence to SCIP infection-prevention process-of-care measures (using the 2 composite scores of S-INF and S-INF-Core) to predict postoperative infections. RESULTS: There were 3996 documented postoperative infections. The S-INF composite process-of-care measure predicted a decrease in postoperative infection rates from 14.2 to 6.8 per 1000 discharges (adjusted odds ratio, 0.85; 95% confidence interval, 0.76-0.95). The S-INF-Core composite process-of-care measure predicted a decrease in postoperative infection rates from 11.5 to 5.3 per 1000 discharges (adjusted odds ratio, 0.86; 95% confidence interval, 0.74-1.01), which was not a statistically significantly lower probability of infection. None of the individual SCIP measures were significantly associated with a lower probability of infection. CONCLUSIONS: Among hospitals in the Premier Inc Perspective Database reporting SCIP performance, adherence measured through a global all-or-none composite infection-prevention score was associated with a lower probability of developing a postoperative infection. However, adherence reported on individual SCIP measures, which is the only form in which performance is publicly reported, was not associated with a significantly lower probability of infection.

Melatonin for cognitive impairment.

BACKGROUND: There are a number of studies that suggest a relationship between decline of melatonin function and the symptoms of dementia. OBJECTIVES: The review assessed the evidence of clinical efficacy and safety of melatonin in the treatment of manifestations of dementia or cognitive impairment (CI). SEARCH STRATEGY: The Cochrane Dementia and Cognitive Improvement Group's Specialized Register was searched for trials involving melatonin on 5 October 2005. The search terms used were MELATONIN, and N-ACETYL-5-METHOXYTRYPTAMINE. This Register contains records from all major health care databases as well as many ongoing trials databases and is updated regularly. SELECTION CRITERIA: All relevant, randomized controlled trials in which orally administered melatonin in any dosage was compared with a control group for the effect on managing cognitive, behavioural (excluding sleep), and/or affective disturbances of people with dementia of any degree of severity. DATA COLLECTION AND ANALYSIS: Two to three reviewers independently assessed the retrieved articles for relevance and methodological quality, and extracted data from the selected studies. Statistically significant differences in changes in outcomes from baseline to end of treatment between the melatonin and control groups were examined. Each study was summarized using a measure of effect (e.g. mean difference) and meta-analyses were conducted when appropriate. MAIN RESULTS: Three studies met the inclusion criteria. This review revealed non-significant effects from the pooled estimates of MMSE cognitive, and ADAS-cognitive change scores. Individual study estimates for treatment effect demonstrated a significant improvement for melatonin compared with placebo in behavioural and affective symptoms as measured by the ADAS non-cognitive scale in a study of 20 patients, and the Neuropsychiatric Inventory (NPI) following treatment with 2.5 mg/day (SR) melatonin, but not with 10mg/day (IR) melatonin in a larger study of 157 patients. The remainder of the treatment effects for affect, behaviour and activities of daily living were non-significant. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the effectiveness of melatonin in managing the cognitive and non-cognitive sequelae of dementia.

Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea.

OBJECTIVES: Distinguishing between irritable bowel syndrome (IBS) and functional dyspepsia can be challenging because of the variations in symptom patterns, which commonly overlap. However, the overlap is poorly quantified, and it is equally uncertain whether symptom patterns differ in subgroups of IBS arbitrarily defined by primary bowel patterns of constipation (IBS-C) and diarrhea (IBS-D). We aimed to determine and to compare the distribution of GI symptoms, both, upper and lower, among IBS-C and IBS-D patients. METHODS: A total of 121 consecutive patients presenting with a diagnosis of IBS were grouped according to primary bowel symptoms as IBS-C (58 women and 18 men, mean age 47 +/- 17 yr) or IBS-D (26 women and 19 men, mean age 47 +/- 15 yr). The Hopkins Bowel Symptom Questionnaire, which includes a brief Quality of Life assessment, and the Hopkins Symptom Checklist 90-Revised were completed by all patients at intake. RESULTS: IBS-C patients reported significantly more overall GI symptoms when compared to patients with IBS-D (6.67 vs 4.62, respectively, p<0.001). Abdominal pain patterns differed in patients with IBS-C versus IBS-D (lower abdominal pain: 40.8% vs 24.4% p=0.05 and upper abdominal pain: 36.8% vs 24.4%, respectively). Bloating was substantially more common in IBS-C patients (75%) than in IBS-D (40.9%). There were no significant differences in personality subscales by IBS subgroup; however, somatization was positively associated with multiple symptom reports and was negatively correlated with quality of life. CONCLUSIONS: Upper GI symptoms consistent with functional dyspepsia were more frequent in IBS-C. Although there was considerable overlap of upper and lower GI symptoms in patients with IBS-C and IBS-D, the former had more frequent lower abdominal pain and bloating.

Infection of the macrophage cell line NR8383 with Mycobacterium tuberculosis (H37Ra) leads to an increase in oligodeoxynucleotide accumulation.

Mycobacterium tuberculosis infection continues to be a daunting clinical challenge. Although it may well be one of the most studied bacteria in history, several aspects of its pathology remain a mystery. The resurgence of drug-resistant M. tuberculosis strains and with its unusual pathology have promoted a renewed basic and clinical research interest in developing new therapies to combat this pathogen. The primary localization site for M. tuberculosis is within alveolar macrophages. Drug delivery strategies and novel therapeutic agents designed to target alveolar macrophages may lead to efficient destruction of M. tuberculosis. Oligodeoxynucleotides (ODN) are short segments of nucleic acids that can interfere with transcription and translation processes. In this report, a monocyte-macrophage cell line was characterized in regard to ODN transport in the presence or absence of M. tuberculosis infection. The cells accumulated ODN in a time-dependent and concentration-dependent manner, regardless of the presence of serum. After 4 hours of incubation with M. tuberculosis (multiplicity of infection [MOI] 10:1), infected NR8383 cells demonstrated 1.5-7-fold increase in fluorescein isothiocyanate (FITC)-labeled phosphorothioate ODN accumulation as measured by flow cytometry. The increase in uptake was associated only with fluorescent-labeled ODN and not labeled markers of fluid phase endocytosis (e.g., tetramethylrhodamine isothiocyanate [TRITC], FITC-labeled dextran). NR8383 cells activated by phytohemagglutinin (PHA) did not demonstrate a significant increase in the uptake of either FITC-labeled dextran or FITC-labeled ODN. These studies demonstrate that NR8383 cells that have been infected with M. tuberculosis can specifically accumulate ODN, and this route of accumulation may lead to a means of drug targeting to mycobacteria-containing cells.

Effects of insulin-like growth factor I treatment on statural growth, body composition and phenotype of children with growth hormone insensitivity syndrome. GHIS Collaborative Group.

Eight children with growth hormone insensitivity syndrome (GHIS) have been treated with injections of recombinant human insulin-like growth factor I (rhIGF-I) for more than 5 years each. After good acceleration of growth in the first year of therapy, the growth rate decreased to an average of 5-6 cm/year. In general, growth with IGF-I therapy is less exuberant than that observed with growth hormone (GH) therapy in GH-deficient children. IGF is well tolerated, though there may be overgrowth of the lymphoid tissues and the kidneys. Bone mineral density is improved by treatment. The benefits of therapy appear to exceed the risks.